Assessment of Elemental Impurities Level After Chronic Administration of Diosmectite (SMECTA®) in Subjects With Chronic Diarrhoea
| Registry | NCT03045926 |
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| Status | Completed |
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| Phase | Phase 1 |
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| Study type | Interventional; na, single group, masking: none, other |
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| Enrollment | 35 (Actual) |
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| Sponsor | Ipsen (Industry) |
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| Conditions | Chronic Functional Diarrhea of Unknown Origin |
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| Interventions | Diosmectite (Smecta®) (Drug) |
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| Dates | start 2016-08-01, primary completion 2017-05-09, completion 2017-05-09, first posted 2017-02-08, last updated 2019-04-05 |
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| Locations | 2 sites in Netherlands, United Kingdom |
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-Summary
The main purpose of this study is to assess the concentration of elemental impurities in blood and urine after chronic administration of Smecta® in subjects with chronic functional diarrhoea. For exploratory purposes, the potential effects of diosmectite on bowel microbiote composition will be investigated.
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+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Diosmectite (Smecta®) | Experimental | Drug: Diosmectite (Smecta®) | 5 weeks of diosmectite 3g, 3 times daily. |
- Diosmectite (Smecta®) (Drug)
+Outcome measures
Primary outcomes
- Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood lead levels (BLL) were defined as the average between the available screening and pre-dose (Day-1) values. Values below the limit of detection (LOD) or below the lower limit of quantification (LLOQ) were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in BLL during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in BLL during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
Secondary outcomes
- Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood aluminium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood aluminium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood aluminium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood arsenic concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood arsenic concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood arsenic concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood barium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood barium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood barium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood cadmium concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood cadmium concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood cadmium concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood cobalt concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood cobalt concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood cobalt concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood mercury concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood mercury concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood mercury concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 125.]: Baseline blood nickel concentrations were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in blood nickel concentrations during the treatment period is presented for the timepoints: 2 hours after the first dose, and prior to and after the second and third doses on Days 1 and 35, prior to the first dose on Days 2, 8, 15, 22 and 29, and on Day 36 in the morning.
The absolute mean change from baseline in blood nickel concentrations during the post-treatment follow-up period is presented for the timepoints: Day 65, Day 95, and Day 125 (End of Study).
- Mean Change From Baseline in Urine Lead Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine lead levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine lead levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Aluminium Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine aluminium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine aluminium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Arsenic Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine arsenic levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine arsenic levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Barium Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine barium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine barium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Cadmium Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine cadmium levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine cadmium levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Cobalt Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine cobalt levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine cobalt levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Mercury Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine mercury levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine mercury levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
- Mean Change From Baseline in Urine Nickel Levels During the Treatment Period and Post-treatment Follow-up Period [Screening and pre-dose Day -1 up to Day 95.]: Baseline urine nickel levels were defined as the average between the available screening and pre-dose (Day-1) values. Values below the LOD or below the LLOQ were replaced by LOD/2 or LLOQ/2 values.
The absolute mean change from baseline in urine nickel levels are presented for Day 35 of the treatment period (Visit 7, Week 5), and Day 65 (Visit 8, Week 9) and Day 95 (Visit 9, Week 13) in the post-treatment follow-up.
+Eligibility
Sex: All, ages: 18 Years to 60 Years
Inclusion Criteria:
* Male or female subjects, between 18 and 60 years old inclusive, BMI between 19 and 32 kg/m2 inclusive (minimum body weight of 50 kg at screening).
* Functional chronic diarrhoea defined as loose or watery stools occurring in at least 75% of stools for the last 3 months (with symptom onset at least 6 months before diagnosis).
Exclusion Criteria:
* No history of suspected organic or drug induced cause to chronic diarrhoea.
+Posted results
Participant flow
| Milestone | Smecta® Powder |
|---|
| Started | 35 |
| Completed | 35 |
| Not completed | 0 |
Outcome results
- Mean Change From Baseline in Blood Lead Levels During the Treatment Period and Post-treatment Follow-up Period (Primary), Mean, nanograms per millilitre (ng/mL): Smecta® Powder 0.120 (-0.823 to 1.063)
- Mean Change From Baseline in Blood Aluminium Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -14.958 (-30.930 to 1.014)
- Mean Change From Baseline in Blood Arsenic Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -0.029 (-0.285 to 0.227)
- Mean Change From Baseline in Blood Barium Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.229 (-0.095 to 0.552)
- Mean Change From Baseline in Blood Cadmium Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.017 (-0.018 to 0.053)
- Mean Change From Baseline in Blood Cobalt Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.006 (-0.037 to 0.050)
- Mean Change From Baseline in Blood Mercury Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -0.017 (-0.064 to 0.031)
- Mean Change From Baseline in Blood Nickel Concentrations During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.000 (-0.562 to 0.562)
- Mean Change From Baseline in Urine Lead Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.040 (-0.168 to 0.248)
- Mean Change From Baseline in Urine Aluminium Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.700 (-0.723 to 2.123)
- Mean Change From Baseline in Urine Arsenic Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -2.694 (-22.005 to 16.618)
- Mean Change From Baseline in Urine Barium Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 1.493 (0.917 to 2.070)
- Mean Change From Baseline in Urine Cadmium Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -0.051 (-0.114 to 0.011)
- Mean Change From Baseline in Urine Cobalt Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder 0.045 (-0.067 to 0.156)
- Mean Change From Baseline in Urine Mercury Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -0.049 (-0.117 to 0.020)
- Mean Change From Baseline in Urine Nickel Levels During the Treatment Period and Post-treatment Follow-up Period (Secondary), Mean, ng/mL: Smecta® Powder -0.090 (-0.423 to 0.243)
Adverse events
Time frame: Treatment emergent adverse events (TEAEs) were collected from Day 1 up to Day 125 (End of Study).
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| Smecta® Powder | 0/35 (0.0%) | 0/35 (0.0%) | 30/35 (85.7%) |
Other adverse events by term
| Term | Organ system | Smecta® Powder |
|---|
| Headache | Nervous system disorders | 13/35 |
| Dizziness | Nervous system disorders | 1/35 |
| Migraine | Nervous system disorders | 1/35 |
| Somnolence | Nervous system disorders | 1/35 |
| Nasopharyngitis | Infections and infestations | 9/35 |
| Gastroenteritis | Infections and infestations | 2/35 |
| Upper respiratory tract infection | Infections and infestations | 2/35 |
| Cystitis | Infections and infestations | 1/35 |
| Influenza | Infections and infestations | 1/35 |
| Otitis media | Infections and infestations | 1/35 |
| Tooth abscess | Infections and infestations | 1/35 |
| Constipation | Gastrointestinal disorders | 5/35 |
| Diarrhoea | Gastrointestinal disorders | 4/35 |
| Abdominal pain | Gastrointestinal disorders | 3/35 |
| Flatulence | Gastrointestinal disorders | 2/35 |
| Mouth ulceration | Gastrointestinal disorders | 2/35 |
| Abdominal distension | Gastrointestinal disorders | 1/35 |
| Anal fissure | Gastrointestinal disorders | 1/35 |
| Dyspepsia | Gastrointestinal disorders | 1/35 |
| Frequent bowel movements | Gastrointestinal disorders | 1/35 |
| Irritable bowel syndrome | Gastrointestinal disorders | 1/35 |
| Influenza like illness | General disorders | 3/35 |
| Fatigue | General disorders | 2/35 |
| Pyrexia | General disorders | 2/35 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 5/35 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2/35 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 1/35 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1/35 |
| Pruritus | Skin and subcutaneous tissue disorders | 2/35 |
| Dry skin | Skin and subcutaneous tissue disorders | 1/35 |
| Eczema | Skin and subcutaneous tissue disorders | 1/35 |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 1/35 |
| Onycholasis | Skin and subcutaneous tissue disorders | 1/35 |
| Blood glucose increased | Investigations | 2/35 |
| Transferrin increased | Investigations | 2/35 |
| Blood iron increased | Investigations | 1/35 |
| Gamma-glutamyltransferase increased | Investigations | 1/35 |
| Back pain | Musculoskeletal and connective tissue disorders | 2/35 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1/35 |
| Flank pain | Musculoskeletal and connective tissue disorders | 1/35 |
| Synovial cyst | Musculoskeletal and connective tissue disorders | 1/35 |
| Chemical injury | Injury, poisoning and procedural complications | 1/35 |
| Contusion | Injury, poisoning and procedural complications | 1/35 |
| Skin abrasion | Injury, poisoning and procedural complications | 1/35 |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | 1/35 |
| Haematuria | Renal and urinary disorders | 1/35 |
Limitations and caveats: The validity of the analytical methods for vanadium determination in human whole blood and urine was not demonstrated. Therefore, no result for vanadium concentration in the clinical samples is reported.
+Locations (2)
| Facility | City | Country | Status |
|---|
| PRA Health Sciences | Groningen | Netherlands | |
| MAC Clinical Research Limited | Manchester | United Kingdom | |
+Publications
- Results publication: Da Silva K, Guilly S, Thirion F, Le Chatelier E, Pons N, Roume H, Quinquis B, Ehrlich SD, Bekkat N, Mathiex-Fortunet H, Sokol H, Dore J. Long-term diosmectite use does not alter the gut microbiota in adults with chronic diarrhea. BMC Microbiol. 2022 Feb 12;22(1):54. doi: 10.1186/s12866-022-02464-7. PMID 35151268
+Study documents
+Investigators
- Ipsen Medical Director, Study director, Ipsen
+Funding