A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults

NCT03201419 — Phase 2, Completed, 302 participants, Ferring Pharmaceuticals

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

A Randomised, Double-blind, Placebo-controlled, Response-adaptive Dose-finding Trial Investigating the Efficacy, Safety and Tolerability of Oral Doses of FE 201836, With Desmopressin Orally Disintegrating Tablet as a Benchmark, During 12 Weeks of Treatment for Nocturia Due to Nocturnal Polyuria in Adults

Registry	NCT03201419
Status	Completed
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	302 (Actual)
Sponsor	Ferring Pharmaceuticals (Industry)
Conditions	Nocturia
Interventions	FE 201836, Desmopressin, Placebo oral solution, Placebo ODT (Drug)
Dates	start 2017-07-27, primary completion 2019-10-31, completion 2019-10-31, first posted 2017-06-28, last updated 2022-03-02
Locations	72 sites in United States, Belgium, Canada, Czechia, Germany, Hungary, Poland

-Summary

The purpose of this trial was to investigate the efficacy, safety and tolerability of different oral doses of FE 201836, with desmopressin as a benchmark, during 12 weeks of treatment for nocturia due to nocturnal polyuria in adults

Expand all sections · Collapse all

+Arms and interventions

Arm	Type	Interventions	Description
FE 201836 500 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT), administered once daily
FE 201836 350 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 350 μg oral solution and placebo ODT, administered once daily
FE 201836 250 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 250 μg oral solution and placebo ODT, administered once daily
FE 201836 150 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 150 μg oral solution and placebo ODT, administered once daily
FE 201836 100 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 100 μg oral solution and placebo ODT, administered once daily
FE 201836 50 μg (Randomized Treatment Period)	Experimental	Drug: FE 201836; Drug: Placebo ODT	FE 201836 50 μg oral solution and placebo ODT, administered once daily
Placebo (Randomized Treatment Period)	Experimental	Drug: Placebo oral solution; Drug: Placebo ODT	Placebo oral solution and placebo ODT, administered once daily
Desmopressin 25 μg (Randomized Treatment Period)	Experimental	Drug: Desmopressin; Drug: Placebo oral solution	Desmopressin 25 μg ODT and placebo oral solution, administered once daily (female subjects)
Desmopressin 50 μg (Randomized Treatment Period)	Experimental	Drug: Desmopressin; Drug: Placebo oral solution	Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)

FE 201836 (Drug), also known as Velmupressin: Oral solution for daily intake
Desmopressin (Drug), also known as NOCDURNA: Desmopressin Orally Disintegrating Tablet (ODT)
Placebo oral solution (Drug): Manufactured to mimic experimental drug
Placebo ODT (Drug): Manufactured to mimic experimental drug

+Outcome measures

Primary outcomes

Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment [Baseline, during 12 weeks of treatment]: Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean number of nocturnal voids equal to 2, and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint.

Secondary outcomes

Change From Baseline in Mean Number of Nocturnal Voids at Week 1 [Baseline, Week 1]: Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2. MMRM=Mixed Model for Repeated Measurements. For all visit-specific results, the tables present the number of subjects with an observation of the endpoints in question at the specific visit. All secondary analyses are performed using the observed-case approach based on repeated measurements for all subjects in the ITT-RT population. That is, these secondary analyses are based on all subjects with at least one non-missing post-baseline observation (with a baseline value if relevant).
Change From Baseline in Mean Number of Nocturnal Voids at Week 4 [Baseline, Week 4]: Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Change From Baseline in Mean Number of Nocturnal Voids at Week 8 [Baseline, Week 8]: Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Change From Baseline in Mean Number of Nocturnal Voids at Week 12 [Baseline, Week 12]: Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.
Responder Rate in Nocturnal Voids at Week 1 [Week 1]: Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% in the reduction mean number of nocturnal voids are estimated using a baseline value of 2. The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 4 [Week 4]: Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2. The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 8 [Week 8]: Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2. The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids at Week 12 [Week 12]: Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2. The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Responder Rate in Nocturnal Voids During 12 Weeks of Treatment [During 12 weeks of treatment]: Defined as 50% reduction in nocturnal voids from baseline. Estimated odds of at least 50% reduction in the aggregated mean number of nocturnal voids for a subject with 2 nocturnal voids at baseline are presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint. The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).
Change From Baseline in Mean NI Diary Total Score at Week 1 [Baseline, Week 1]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall quality of life (QoL) impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items.Responses are scored from 0 to 4 (lowest t o highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 4 [Baseline, Week 4]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 8 [Baseline, Week 8]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Total Score at Week 12 [Baseline, Week 12]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.
Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment [Baseline, during 12 weeks of treatment]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the mean over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean NI Diary Total Score equal to 40 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment [During 12 weeks of treatment]: The percentages of nights during the treatment period with at most one nocturnal void are presented in this endpoint. Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment [During 12 weeks of treatment]: The percentages of nights during the treatment period with complete response, i.e. no nocturnal voids are presented in this endpoint. Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 [Baseline, Week 1]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 [Baseline, Week 4]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 [Baseline, Week 8]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 [Baseline, Week 12]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.
Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment [Baseline, during 12 weeks of treatment]: The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean NI Diary Overall Impact Score equal to 40 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 [Week 1]: The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 [Week 4]: The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 [Week 8]: The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 [Week 12]: The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint.
Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 [Baseline, Week 1]: The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 4 [Baseline, Week 4]: The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 8 [Baseline, Week 8]: The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in PGI-S Scores at Week 12 [Baseline, Week 12]: The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 [Baseline, Week 1]: The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 [Baseline, Week 4]: The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 [Baseline, Week 8]: The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 [Baseline, Week 12]: The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.
Change From Baseline in ISI at Week 4 [Baseline, Week 4]: The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in ISI at Week 8 [Baseline, Week 8]: The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in ISI at Week 12 [Baseline, Week 12]: The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 [Baseline, Week 1]: The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occured. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 4 [Baseline, Week 4]: The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 8 [Baseline, Week 8]: The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Mean Duration of FUSP at Week 12 [Baseline, Week 12]: The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).
Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment [Baseline, During 12 Weeks of Treatment]: The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean duration of FUSP (minutes) equal to 180 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 [Baseline, Week 1]: The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed. Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented. Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 [Baseline, Week 12]: The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed. Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented. Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.
Change From Baseline in Mean NUV in Week 1 [Baseline, Week 1]: The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning. The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).
Change From Baseline in Mean NUV at Week 12 [Baseline, Week 12]: The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning. The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults ≥18 years of age (at the time of written consent)
* Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1
* ≥2 nocturnal voids (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2
* The largest single voided volume must be ≥200 mL (at least 1 void ≥200 mL) as documented in the 3-day e-Diary prior to Visit 2
* Nocturnal polyuria, defined as Nocturnal Polyuria index >33%, a ratio of Nocturnal Urine Volume in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2
* ≥20% decrease in the nocturnal diuresis rate (mL/min) (that was recorded at Visit 2) as documented in the 3-day e-Diary prior to Visit 3

Exclusion Criteria:

* Current diagnosis of Obstructive Sleep Apnoea (OSA)
* Restless Legs Syndrome (RLS)
* Bladder Outlet Obstruction (BOO) or urine flow <5 mL/s, as confirmed by uroflowmetry upon suspicion during screening prior to Visit 2
* Urinary incontinence defined as an average of >1 episode/day in the 3-day e-Diary prior to Visit 2 (occasional urge incontinence during daytime or at night on the way to void is not necessarily exclusionary)
* Any pelvic or lower urinary tract surgery and/or radio therapy or previous pelvic irradiation within the past 6 months prior to Visit 1. Including e.g., transurethral resection for Bladder Outlet Obstruction or Benign Prostatic Hyperplasia, hysterectomy or female incontinence procedures
* Genito-urinary tract pathology that can in the investigator's opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder-related pain, chronic pelvic pain syndrome, or stone in the bladder or urethra causing symptoms
* A history of cancer with the last date of disease activity/presence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin
* History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson's, spinal cord injury, spina bifida)
* Habitual (fluid intake >3L per day) or psychogenic polydipsia
* Uncontrolled hypertension, as judged by the investigator
* Uncontrolled diabetes mellitus, as judged by the investigator
* Central or nephrogenic diabetes insipidus
* Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
* History of gastric retention
* Suspicion or evidence of congestive heart failure, (New York Heart Association (NYHA) class II, III, IV)
* Hyponatraemia:

  * Serum sodium level <135 mmol/L at Visit 1(re-tested, with results available within 7 days)
  * Serum sodium level <130 mmol/L at Visit 3 (re-tested, with results available within 7 days)
* Use of any prohibited therapy listed below:

  * Current or former (within 3 months prior to screening) treatment with any other investigational medicinal product (IMP)
  * Unstable electrostimulation or behavioural bladder training program less than 3 months prior to screening (stable electrostimulation or behavioural bladder training program started at least 3 months before screening are acceptable)
  * Thiazide diuretics
  * Antiarrhythmic agents
  * V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)
  * Loperamide
  * Botulinum toxin (cosmetic non-urological use is acceptable)
  * Valproate

+Posted results

Participant flow

Milestone	FE 201836 500 µg (Randomized Treatment Period)	FE 201836 350 µg (Randomized Treatment Period)	FE 201836 250 µg (Randomized Treatment Period)	FE 201836 150 µg (Randomized Treatment Period)	FE 201836 100 µg (Randomized Treatment Period)	FE 201836 50 µg (Randomized Treatment Period)	Placebo (Randomized Treatment Period)	Desmopressin 25 µg (Randomized Treatment Period)	Desmopressin 50 µg (Randomized Treatment Period)
Started	60	27	24	14	13	34	87	26	17
Completed	52	24	22	14	12	33	81	25	15
Not completed	8	3	2	0	1	1	6	1	2

Outcome results

Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment (Primary), Mean, nocturnal voids: FE 201836 500 ug (Randomized Treatment Period) -1.06 (-1.28 to -0.86); FE 201836 350 ug (Randomized Treatment Period) -0.99 (-1.20 to -0.78); FE 201836 250 ug (Randomized Treatment Period) -0.89 (-1.12 to -0.69); FE 201836 150 ug (Randomized Treatment Period) -0.80 (-1.00 to -0.62); FE 201836 100 ug (Randomized Treatment Period) -0.77 (-0.97 to -0.59); FE 201836 50 ug (Randomized Treatment Period) -0.76 (-0.95 to -0.58); Placebo (Randomized Treatment Period) -0.76 (-0.95 to -0.58)
Change From Baseline in Mean Number of Nocturnal Voids at Week 1 (Secondary), Mean, nocturnal voids: FE 201836 500 ug (Randomized Treatment Period) -0.714 (-1.005 to -0.424); FE 201836 350 ug (Randomized Treatment Period) -1.162 (-1.577 to -0.747); FE 201836 250 ug (Randomized Treatment Period) -0.722 (-1.149 to -0.296); FE 201836 150 ug (Randomized Treatment Period) -0.520 (-1.058 to 0.017); FE 201836 100 ug (Randomized Treatment Period) -0.722 (-1.318 to -0.126); FE 201836 50 ug (Randomized Treatment Period) -0.325 (-0.709 to 0.059); Placebo (Randomized Treatment Period) -0.575 (-0.842 to -0.308) (p 0.4214)
Change From Baseline in Mean Number of Nocturnal Voids at Week 4 (Secondary), Mean, nocturnal voids: FE 201836 500 ug (Randomized Treatment Period) -1.078 (-1.345 to -0.811); FE 201836 350 ug (Randomized Treatment Period) -1.330 (-1.708 to -0.952); FE 201836 250 ug (Randomized Treatment Period) -0.784 (-1.181 to -0.386); FE 201836 150 ug (Randomized Treatment Period) -0.471 (-0.969 to 0.028); FE 201836 100 ug (Randomized Treatment Period) -0.952 (-1.469 to -0.435); FE 201836 50 ug (Randomized Treatment Period) -0.518 (-0.866 to -0.171); Placebo (Randomized Treatment Period) -0.912 (-1.152 to -0.673) (p 0.2909)
Change From Baseline in Mean Number of Nocturnal Voids at Week 8 (Secondary), Mean, nocturnal voids: FE 201836 500 ug (Randomized Treatment Period) -1.085 (-1.394 to -0.776); FE 201836 350 ug (Randomized Treatment Period) -1.177 (-1.603 to -0.751); FE 201836 250 ug (Randomized Treatment Period) -0.965 (-1.414 to -0.516); FE 201836 150 ug (Randomized Treatment Period) -0.490 (-1.037 to 0.058); FE 201836 100 ug (Randomized Treatment Period) -1.077 (-1.671 to -0.484); FE 201836 50 ug (Randomized Treatment Period) -0.786 (-1.187 to -0.386); Placebo (Randomized Treatment Period) -0.953 (-1.233 to -0.672) (p 0.4732)
Change From Baseline in Mean Number of Nocturnal Voids at Week 12 (Secondary), Mean, nocturnal voids: FE 201836 500 ug (Randomized Treatment Period) -1.256 (-1.568 to -0.944); FE 201836 350 ug (Randomized Treatment Period) -1.120 (-1.558 to -0.683); FE 201836 250 ug (Randomized Treatment Period) -0.850 (-1.301 to -0.400); FE 201836 150 ug (Randomized Treatment Period) -0.674 (-1.206 to -0.142); FE 201836 100 ug (Randomized Treatment Period) -1.053 (-1.650 to -0.456); FE 201836 50 ug (Randomized Treatment Period) -0.921 (-1.317 to -0.524); Placebo (Randomized Treatment Period) -0.957 (-1.237 to -0.677) (p 0.1106)
Responder Rate in Nocturnal Voids at Week 1 (Secondary), Mean, odd of response: FE 201836 500 ug (Randomized Treatment Period) 0.844 (0.457 to 1.558); FE 201836 350 ug (Randomized Treatment Period) 1.202 (0.510 to 2.833); FE 201836 250 ug (Randomized Treatment Period) 0.682 (0.280 to 1.662); FE 201836 150 ug (Randomized Treatment Period) 0.818 (0.269 to 2.490); FE 201836 100 ug (Randomized Treatment Period) 0.810 (0.240 to 2.738); FE 201836 50 ug (Randomized Treatment Period) 0.513 (0.227 to 1.157); Placebo (Randomized Treatment Period) 0.480 (0.272 to 0.848) (p 0.117)
Responder Rate in Nocturnal Voids at Week 4 (Secondary), Mean, odd of response: FE 201836 500 ug (Randomized Treatment Period) 1.199 (0.633 to 2.270); FE 201836 350 ug (Randomized Treatment Period) 5.851 (1.511 to 22.650); FE 201836 250 ug (Randomized Treatment Period) 0.634 (0.255 to 1.575); FE 201836 150 ug (Randomized Treatment Period) 0.534 (0.165 to 1.731); FE 201836 100 ug (Randomized Treatment Period) 1.760 (0.470 to 6.596); FE 201836 50 ug (Randomized Treatment Period) 0.683 (0.301 to 1.550); Placebo (Randomized Treatment Period) 1.235 (0.686 to 2.224) (p 0.937)
Responder Rate in Nocturnal Voids at Week 8 (Secondary), Mean, odd of response: FE 201836 500 ug (Randomized Treatment Period) 1.395 (0.717 to 2.715); FE 201836 350 ug (Randomized Treatment Period) 3.398 (1.150 to 10.043); FE 201836 250 ug (Randomized Treatment Period) 1.928 (0.721 to 5.155); FE 201836 150 ug (Randomized Treatment Period) 0.877 (0.286 to 2.688); FE 201836 100 ug (Randomized Treatment Period) 1.039 (0.302 to 3.569); FE 201836 50 ug (Randomized Treatment Period) 1.489 (0.638 to 3.474); Placebo (Randomized Treatment Period) 1.503 (0.806 to 2.803) (p 0.850)
Responder Rate in Nocturnal Voids at Week 12 (Secondary), Mean, odd of response: FE 201836 500 ug (Randomized Treatment Period) 3.914 (1.830 to 8.370); FE 201836 350 ug (Randomized Treatment Period) 1.891 (0.693 to 5.163); FE 201836 250 ug (Randomized Treatment Period) 1.824 (0.694 to 4.795); FE 201836 150 ug (Randomized Treatment Period) 0.854 (0.279 to 2.611); FE 201836 100 ug (Randomized Treatment Period) 1.400 (0.401 to 4.893); FE 201836 50 ug (Randomized Treatment Period) 1.395 (0.611 to 3.181); Placebo (Randomized Treatment Period) 1.590 (0.844 to 2.993) (p 0.046)
Responder Rate in Nocturnal Voids During 12 Weeks of Treatment (Secondary), Mean, odd of response: FE 201836 500 ug (Randomized Treatment Period) 1.129 (0.808 to 1.753); FE 201836 350 ug (Randomized Treatment Period) 1.095 (0.772 to 1.661); FE 201836 250 ug (Randomized Treatment Period) 1.032 (0.711 to 1.543); FE 201836 150 ug (Randomized Treatment Period) 0.934 (0.597 to 1.378); FE 201836 100 ug (Randomized Treatment Period) 0.887 (0.555 to 1.253); FE 201836 50 ug (Randomized Treatment Period) 0.849 (0.534 to 1.187); Placebo (Randomized Treatment Period) 0.834 (0.514 to 1.180)
Change From Baseline in Mean NI Diary Total Score at Week 1 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -7.55 (-11.67 to -3.43); FE 201836 350 ug (Randomized Treatment Period) -21.91 (-28.15 to -15.68); FE 201836 250 ug (Randomized Treatment Period) -10.90 (-17.17 to -4.63); FE 201836 150 ug (Randomized Treatment Period) -8.93 (-17.15 to -0.72); FE 201836 100 ug (Randomized Treatment Period) -9.68 (-18.41 to -0.94); FE 201836 50 ug (Randomized Treatment Period) -8.75 (-14.27 to -3.23); Placebo (Randomized Treatment Period) -8.07 (-11.48 to -4.65) (p 0.8463)
Change From Baseline in Mean NI Diary Total Score at Week 4 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -12.62 (-16.89 to -8.35); FE 201836 350 ug (Randomized Treatment Period) -17.44 (-23.80 to -11.08); FE 201836 250 ug (Randomized Treatment Period) -14.37 (-20.96 to -7.78); FE 201836 150 ug (Randomized Treatment Period) -11.23 (-19.82 to -2.65); FE 201836 100 ug (Randomized Treatment Period) -22.23 (-31.11 to -13.35); FE 201836 50 ug (Randomized Treatment Period) -13.29 (-19.00 to -7.58); Placebo (Randomized Treatment Period) -14.20 (-17.77 to -10.64) (p 0.5695)
Change From Baseline in Mean NI Diary Total Score at Week 8 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -16.03 (-20.49 to -11.57); FE 201836 350 ug (Randomized Treatment Period) -23.22 (-29.79 to -16.64); FE 201836 250 ug (Randomized Treatment Period) -15.10 (-21.85 to -8.35); FE 201836 150 ug (Randomized Treatment Period) -12.04 (-20.77 to -3.32); FE 201836 100 ug (Randomized Treatment Period) -19.23 (-28.62 to -9.83); FE 201836 50 ug (Randomized Treatment Period) -14.11 (-20.00 to -8.22); Placebo (Randomized Treatment Period) -14.83 (-18.50 to -11.16) (p 0.6792)
Change From Baseline in Mean NI Diary Total Score at Week 12 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -16.92 (-21.66 to -12.18); FE 201836 350 ug (Randomized Treatment Period) -24.44 (-31.52 to -17.35); FE 201836 250 ug (Randomized Treatment Period) -14.68 (-21.94 to -7.42); FE 201836 150 ug (Randomized Treatment Period) -10.13 (-19.37 to -0.88); FE 201836 100 ug (Randomized Treatment Period) -22.59 (-32.46 to -12.71); FE 201836 50 ug (Randomized Treatment Period) -17.18 (-23.39 to -10.96); Placebo (Randomized Treatment Period) -17.45 (-21.36 to -13.53) (p 0.8646)
Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment (Secondary), Median, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -12.40 (-14.71 to -8.59); FE 201836 350 ug (Randomized Treatment Period) -12.69 (-15.07 to -10.53); FE 201836 250 ug (Randomized Treatment Period) -12.75 (-15.16 to -10.57); FE 201836 150 ug (Randomized Treatment Period) -12.77 (-15.21 to -10.59); FE 201836 100 ug (Randomized Treatment Period) -12.77 (-15.23 to -10.54); FE 201836 50 ug (Randomized Treatment Period) -12.78 (-15.18 to -10.50); Placebo (Randomized Treatment Period) -12.77 (-15.18 to -10.47)
Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment (Secondary), Mean, percentage of nights: FE 201836 500 ug (Randomized Treatment Period) 67.2 (58.2 to 76.2); FE 201836 350 ug (Randomized Treatment Period) 77.5 (64.9 to 90.2); FE 201836 250 ug (Randomized Treatment Period) 64.5 (51.0 to 78.0); FE 201836 150 ug (Randomized Treatment Period) 55.3 (38.3 to 72.3); FE 201836 100 ug (Randomized Treatment Period) 73.2 (55.1 to 91.2); FE 201836 50 ug (Randomized Treatment Period) 61.4 (49.3 to 73.5); Placebo (Randomized Treatment Period) 62.0 (53.8 to 70.2) (p 0.3328)
Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment (Secondary), Mean, percentage of nights: FE 201836 500 ug (Randomized Treatment Period) 23.3 (16.3 to 30.3); FE 201836 350 ug (Randomized Treatment Period) 28.8 (19.0 to 38.6); FE 201836 250 ug (Randomized Treatment Period) 17.3 (6.8 to 27.8); FE 201836 150 ug (Randomized Treatment Period) 12.9 (-0.3 to 26.1); FE 201836 100 ug (Randomized Treatment Period) 14.8 (0.8 to 28.8); FE 201836 50 ug (Randomized Treatment Period) 21.5 (12.1 to 30.9); Placebo (Randomized Treatment Period) 23.0 (16.6 to 29.4) (p 0.9499)
Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -10.98 (-16.40 to -5.56); FE 201836 350 ug (Randomized Treatment Period) -30.39 (-38.62 to -22.17); FE 201836 250 ug (Randomized Treatment Period) -15.51 (-23.85 to -7.17); FE 201836 150 ug (Randomized Treatment Period) -11.77 (-22.69 to -0.85); FE 201836 100 ug (Randomized Treatment Period) -2.79 (-14.29 to 8.70); FE 201836 50 ug (Randomized Treatment Period) -12.26 (-19.57 to -4.95); Placebo (Randomized Treatment Period) -13.46 (-17.89 to -9.03) (p 0.4846)
Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -22.17 (-28.25 to -16.09); FE 201836 350 ug (Randomized Treatment Period) -26.07 (-35.09 to -17.05); FE 201836 250 ug (Randomized Treatment Period) -19.35 (-28.80 to -9.90); FE 201836 150 ug (Randomized Treatment Period) -18.36 (-30.66 to -6.07); FE 201836 100 ug (Randomized Treatment Period) -17.95 (-30.50 to -5.41); FE 201836 50 ug (Randomized Treatment Period) -21.40 (-29.54 to -13.26); Placebo (Randomized Treatment Period) -21.75 (-26.74 to -16.77) (p 0.9175)
Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 (Secondary), Mean, score on a scale: FE 201836 500 ug (Randomized Treatment Period) -28.13 (-34.76 to -21.50); FE 201836 350 ug (Randomized Treatment Period) -34.97 (-44.69 to -25.25); FE 201836 250 ug (Randomized Treatment Period) -21.71 (-31.80 to -11.62); FE 201836 150 ug (Randomized Treatment Period) -19.03 (-32.06 to -6.00); FE 201836 100 ug (Randomized Treatment Period) -23.84 (-37.71 to -9.96); FE 201836 50 ug (Randomized Treatment Period) -20.70 (-29.45 to -11.94); Placebo (Randomized Treatment Period) -25.32 (-30.69 to -19.95) (p 0.5148)
26 more outcome measures not shown.

Adverse events

Time frame: Enrichment period: Treatment-emergent adverse events (AEs) occurring in the time interval from V2 (active run-in) to V4 (randomization), including AEs with missing start date. Randomized treatment period: Treatment-emergent AEs occurring in the time interval from V4 to end-of-trial.

Arm	Deaths	Serious adverse events	Other adverse events
FE 201836 500 µg (Enrichment Period)	0/531 (0.0%)	2/531 (0.4%)	0/531 (0.0%)
FE 201836 500 µg (Randomized Treatment Period)	0/60 (0.0%)	1/60 (1.7%)	16/60 (26.7%)
FE 201836 350 µg (Randomized Treatment Period)	0/27 (0.0%)	2/27 (7.4%)	3/27 (11.1%)
FE 201836 250 µg (Randomized Treatment Period)	0/24 (0.0%)	1/24 (4.2%)	3/24 (12.5%)
FE 201836 150 µg (Randomized Treatment Period)	0/14 (0.0%)	0/14 (0.0%)	8/14 (57.1%)
FE 201836 100 µg (Randomized Treatment Period)	0/13 (0.0%)	1/13 (7.7%)	5/13 (38.5%)
FE 201836 50 µg (Randomized Treatment Period)	0/34 (0.0%)	0/34 (0.0%)	7/34 (20.6%)
Placebo (Randomized Treatment Period)	0/87 (0.0%)	2/87 (2.3%)	16/87 (18.4%)
Desmopressin 25 µg (Randomized Treatment Period)	0/26 (0.0%)	0/26 (0.0%)	8/26 (30.8%)
Desmopressin 50 µg (Randomized Treatment Period)	0/17 (0.0%)	0/17 (0.0%)	9/17 (52.9%)

Serious adverse events by term

Term	Organ system	FE 201836 500 µg (Enrichment Period)	FE 201836 500 µg (Randomized Treatment Period)	FE 201836 350 µg (Randomized Treatment Period)	FE 201836 250 µg (Randomized Treatment Period)	FE 201836 150 µg (Randomized Treatment Period)	FE 201836 100 µg (Randomized Treatment Period)	FE 201836 50 µg (Randomized Treatment Period)	Placebo (Randomized Treatment Period)	Desmopressin 25 µg (Randomized Treatment Period)	Desmopressin 50 µg (Randomized Treatment Period)
Hyponatraemia	Metabolism and nutrition disorders	2/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	1/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Abdominal pain upper	Gastrointestinal disorders	0/531	0/60	0/27	0/24	0/14	1/13	0/34	0/87	0/26	0/17
Colitis	Gastrointestinal disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	0/26	0/17
Serum sickness-like reaction	Immune system disorders	0/531	1/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Gastroenteritis	Infections and infestations	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	0/26	0/17
Staphylococcal infection	Infections and infestations	0/531	0/60	1/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Urinary tract infection	Infections and infestations	0/531	0/60	1/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0/531	0/60	1/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0/531	0/60	1/27	0/24	0/14	0/13	0/34	0/87	0/26	0/17
Syncope	Nervous system disorders	0/531	0/60	0/27	1/24	0/14	0/13	0/34	0/87	0/26	0/17
Pruritus	Skin and subcutaneous tissue disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	0/26	0/17
Urticaria	Skin and subcutaneous tissue disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	0/26	0/17
Facial bones fracture	Injury, poisoning and procedural complications	0/531	0/60	0/27	1/24	0/14	0/13	0/34	0/87	0/26	0/17
Subdural haematoma	Injury, poisoning and procedural complications	0/531	0/60	0/27	1/24	0/14	0/13	0/34	0/87	0/26	0/17

Other adverse events by term

Term	Organ system	FE 201836 500 µg (Enrichment Period)	FE 201836 500 µg (Randomized Treatment Period)	FE 201836 350 µg (Randomized Treatment Period)	FE 201836 250 µg (Randomized Treatment Period)	FE 201836 150 µg (Randomized Treatment Period)	FE 201836 100 µg (Randomized Treatment Period)	FE 201836 50 µg (Randomized Treatment Period)	Placebo (Randomized Treatment Period)	Desmopressin 25 µg (Randomized Treatment Period)	Desmopressin 50 µg (Randomized Treatment Period)
Anaemia	Blood and lymphatic system disorders	0/531	1/60	0/27	0/24	0/14	1/13	1/34	1/87	0/26	0/17
Vertigo	Ear and labyrinth disorders	0/531	0/60	0/27	0/24	0/14	0/13	1/34	0/87	1/26	1/17
Nausea	Gastrointestinal disorders	0/531	3/60	1/27	2/24	0/14	0/13	1/34	3/87	0/26	1/17
Diarrhoea	Gastrointestinal disorders	0/531	2/60	0/27	0/24	1/14	0/13	1/34	1/87	1/26	0/17
Constipation	Gastrointestinal disorders	0/531	0/60	0/27	0/24	1/14	0/13	0/34	0/87	0/26	1/17
Pain	General disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	1/17
Urinary tract infection	Infections and infestations	0/531	3/60	0/27	0/24	0/14	0/13	0/34	0/87	1/26	0/17
Upper respiratory tract infection	Infections and infestations	0/531	0/60	0/27	0/24	1/14	0/13	0/34	1/87	0/26	0/17
Cellulitis	Infections and infestations	0/531	0/60	0/27	0/24	1/14	0/13	0/34	0/87	0/26	0/17
Accidental overdose	Injury, poisoning and procedural complications	0/531	0/60	0/27	1/24	0/14	0/13	1/34	3/87	0/26	4/17
Hand fracture	Injury, poisoning and procedural complications	0/531	0/60	0/27	0/24	0/14	1/13	0/34	0/87	0/26	0/17
Laceration	Injury, poisoning and procedural complications	0/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	1/17
Road traffic accident	Injury, poisoning and procedural complications	0/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	1/17
Weight increased	Investigations	0/531	3/60	0/27	0/24	0/14	0/13	0/34	1/87	1/26	0/17
Gamma-glutamyltransferase increased	Investigations	0/531	2/60	0/27	0/24	2/14	0/13	0/34	0/87	0/26	0/17
Blood creatine phosphokinase increased	Investigations	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	1/26	1/17
Blood sodium decreased	Investigations	0/531	2/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	1/17
Hepatic enzyme increased	Investigations	0/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	3/26	0/17
Alanine aminotransferase increased	Investigations	0/531	0/60	0/27	0/24	2/14	0/13	0/34	0/87	0/26	0/17
Aspartate aminotransferase increased	Investigations	0/531	0/60	0/27	0/24	2/14	0/13	0/34	0/87	0/26	0/17
Blood alkaline phosphatase	Investigations	0/531	0/60	0/27	0/24	1/14	0/13	0/34	0/87	0/26	0/17
Hyponatraemia	Metabolism and nutrition disorders	0/531	3/60	2/27	0/24	0/14	1/13	0/34	0/87	0/26	1/17
Hypoglycaemia	Metabolism and nutrition disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	0/26	1/17
Muscle spasms	Musculoskeletal and connective tissue disorders	0/531	2/60	0/27	0/24	0/14	1/13	0/34	0/87	0/26	0/17
Joint swelling	Musculoskeletal and connective tissue disorders	0/531	0/60	0/27	1/24	1/14	0/13	0/34	0/87	0/26	0/17
Myalgia	Musculoskeletal and connective tissue disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	0/87	0/26	1/17
Headache	Nervous system disorders	0/531	3/60	0/27	0/24	0/14	0/13	1/34	2/87	1/26	0/17
Insomnia	Psychiatric disorders	0/531	0/60	0/27	0/24	0/14	0/13	0/34	1/87	1/26	1/17
Dysuria	Renal and urinary disorders	0/531	0/60	0/27	0/24	1/14	0/13	0/34	1/87	0/26	0/17
Renal impairment	Renal and urinary disorders	0/531	0/60	0/27	0/24	0/14	1/13	0/34	1/87	0/26	0/17
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	0/531	0/60	0/27	0/24	1/14	0/13	0/34	2/87	0/26	0/17
Hypertension	Vascular disorders	0/531	1/60	0/27	0/24	1/14	0/13	1/34	1/87	0/26	0/17
Vomiting	Gastrointestinal disorders	0/531	0/60	0/27	0/24	2/14	0/13	1/34	1/87	0/26	1/17

+Locations (72)

Facility	City	Country
Achieve Clinical Research, LLC	Birmingham, Alabama	United States
Coastal Clinical Research, an AMR company	Mobile, Alabama	United States
Clinical Trials Research	Lincoln, California	United States
Tri Valley Urology Medical Group	Murrieta, California	United States
San Diego Clinical Trials	San Diego, California	United States
Advanced Rx Clinical Research Group, Inc.	Westminster, California	United States
Downtown Women's Health Care	Denver, Colorado	United States
Genitourinary Surgical Consultants, P.C.	Denver, Colorado	United States
South Florida Medical Research	Aventura, Florida	United States
Women's Medical Research Group, LLC	Clearwater, Florida	United States
Tampa Bay Medical Research, Inc.	Clearwater, Florida	United States
Clinical Research of South Florida	Coral Gables, Florida	United States
Avail Clinical Research, LLC	DeLand, Florida	United States
Finlay Medical Research Corp	Greenacres City, Florida	United States
Pharmax Research Clinic	Miami, Florida	United States
Doctors Research Institute Corporation	Miami, Florida	United States
Sanitas Research	Miami, Florida	United States
Bayside Clinical Research LLC	New Port Richey, Florida	United States
Pines Care Research Center, Inc	Pembroke Pines, Florida	United States
Clinical Research Center of Florida	Pompano Beach, Florida	United States
Meridien Research, Inc.	St. Petersburg, Florida	United States
American Health Network of Indiana, LLC	Avon, Indiana	United States
American Health Network of Indiana, LLC	Greenfield, Indiana	United States
Bay State Clinical Trials, Inc.	Watertown, Massachusetts	United States
Beyer Research	Kalamazoo, Michigan	United States
Remedica LLC	Rochester, Michigan	United States
Quality Clinical Research Center, Inc.	Omaha, Nebraska	United States
Clinical Research Consortium, an AMR company	Las Vegas, Nevada	United States
Mid Hudson Medical Research, PLLC	New Windsor, New York	United States
Premier Medical Group of the Hudson Valley, PC	Poughkeepsie, New York	United States
American Health Research, Inc.	Charlotte, North Carolina	United States
Medication Management, LLC	Greensboro, North Carolina	United States
Peters Medical Research	High Point, North Carolina	United States
PMG Research of Raleigh, LLC	Raleigh, North Carolina	United States
PMG Research of Wilmington, LLC	Wilmington, North Carolina	United States
HWC Women's Research Center	Englewood, Ohio	United States
NECCR Primacare Research, LLC	Providence, Rhode Island	United States
Coastal Carolina Research Center, Inc	Mt. Pleasant, South Carolina	United States
PMG Research of Charleston, LLC	Mt. Pleasant, South Carolina	United States
MCA Research - Partner	Houston, Texas	United States
Ericksen Research & Development, LLC	Clinton, Utah	United States
Advanced Research Institute	Ogden, Utah	United States
Clinical Research Associates of Tidewater, an AMR company	Norfolk, Virginia	United States
ULB Hopital Erasme	Brussels	Belgium
UZ Antwerpen	Edegem	Belgium
Universitair Ziekenhuis Gent	Ghent	Belgium
AZ Groeninge - Campus Vercruysselaan	Kortrijk	Belgium
UZ Leuven	Leuven	Belgium
Ultra-Med Inc.	Pointe-Claire, Quebec	Canada
Milestone Research	London	Canada
SKDS Research Inc.	Newmarket	Canada
Clinique Médicale St-Louis (Recherche) inc d/b/a/ Centre de Recherche Saint-Louis	Québec	Canada
DIEX Recherche Quebec Inc.	Québec	Canada
Bluewater Health-Norman Site	Sarnia	Canada
CHUS - Hôpital Fleurimont	Sherbrooke	Canada
DIEX Recherche Sherbrooke Inc.	Sherbrooke	Canada
Ferring Investigational Site	Toronto	Canada
DIEX Recherche Victoriaville Inc.	Victoriaville	Canada
Urologie Benešov - Afimed s.r.o.	Benešov	Czechia
Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy	Brno	Czechia
Krajska nemocnice Liberec, a.s.	Liberec	Czechia
Urocentrum Plzen	Pilsen	Czechia
Thomayerova nemocnice, PARENT	Prague	Czechia
Gemeinschaftspraxis fuer Urologie und Andrologie	Duisburg	Germany
Urologische Gemeinschaftspraxis	Emmendingen	Germany
Klinikum Weiden, Klinik f. Urologie, Andrologie und Kinderurologie	Weiden	Germany
Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest	Hungary
Synexus Magyarorszag Kft.	Budapest	Hungary
Bagoly Egeszseghaz	Kecskemét	Hungary
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz Urologia	Nyíregyháza	Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok	Hungary
Nasz Lekarz Osrodek Badan Klinicznych	Bydgoszcz	Poland

+Publications

Hudgens S, Howerter A, Polek E, Andersson FL. Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting. Qual Life Res. 2022 Jun;31(6):1837-1848. doi: 10.1007/s11136-021-03060-4. Epub 2021 Dec 21. PMID 34932192

+Study documents

Study Protocol (PDF, 2018-07-05)
Statistical Analysis Plan (PDF, 2019-12-12)

+Investigators

Global Clinical Compliance, Study director, Ferring Pharmaceuticals

+Funding

NIH grants: 2016

My Notes

Public

To Read Reading Read