Effects of Triptorelin Pamoate 6-month When Given to Adult Chinese Participants With Advanced Cancer in the Prostate

• Triptorelin pamoate (embonate) salt (Drug), also known as Dipherelin: Triptorelin pamoate 22.5 mg (6-month formulation), i.m. injection, single dose on Day 1.

Primary outcomes

• Percentage of Participants Who Achieved Castrate Levels of Serum Testosterone on Day 29 [Day 29]: Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Achievement of testosterone castration was defined as serum testosterone level <50 nanograms per deciliter (ng/dL) or 1.735 nanomoles/liter (nmol/L). Percentages are rounded off to the tenth decimal place.
• Percentage of Participants Who Maintained the Castrate Levels From Week 8 to Week 24 [From Week 8 to Week 24]: Blood samples were collected to determine the serum testosterone concentrations using a validated, specific and sensitive LC-MS/MS method. Maintenance of castration was defined as serum testosterone level <50 ng/dL or 1.735 nmol/L.

Secondary outcomes

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance [From the first dose of study intervention (Day 1) up to end of study visit (Week 24), approximately 169 days]: An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect, or any other medically important event. TEAEs were AEs with start date on or after the date of study intervention administration and up to 24 weeks after date of first dose of treatment. Local tolerance was assessed 2 hours (+/-15 minutes) after the single injection of 6-month formulation triptorelin by examination of injection site for signs including but not limited to tenderness, erythema, swelling, hematoma, rash, pain, itching and induration.
• Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24 [Baseline (Day 1), Weeks 12 and 24]: Blood samples were collected for the measurement of plasma PSA concentrations. Percent change in PSA was defined as the absolute value of difference between the PSA values at Week 12 and Week 24 and the baseline value divided by the baseline value. Baseline was defined as the last non-missing measurement taken prior to first study intervention administration.
• Time to Maximum Observed Plasma Concentration (Tmax) of Triptorelin Pamoate [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of tmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
• Maximum Observed Plasma Concentration (Cmax) of Triptorelin Pamoate [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of Cmax of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
• Area Under the Plasma Concentration Time Curve From Time 0 to the Visit on Day 169 (AUC0-169) of Triptorelin Pamoate [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of AUC0-169 of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
• Area Under the Plasma Concentration Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Triptorelin Pamoate [Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 and 168 hours post-dose on Day 1, Days 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of AUClast of triptorelin pamoate. The PK parameters were performed using non-compartmental analysis.
• Time to Maximum Observed Plasma Concentration of Testosterone [Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of tmax of testosterone. The PD parameters were performed using non-compartmental analysis.
• Maximum Observed Plasma Concentration of Testosterone [Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of Cmax of testosterone. The PD parameters were performed using non-compartmental analysis.
• Time to Castration of Testosterone [Pre-dose on Day 1 and Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 141 and 169]: Blood samples were collected at specified timepoints for the assessment of tcast of testosterone. tcast was defined as time to reach serum testosterone level <50 ng/dL or 1.735 nmol/L. The PD parameters were performed using non-compartmental analysis.
• Plasma Concentrations of Triptorelin Pamoate [Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24]: Blood samples were collected at specified timepoints for the assessment of plasma concentration of triptorelin pamoate.
• Serum Concentrations of Testosterone [Pre-dose on Day 1 and post-dose at Weeks 4, 8, 12, 16, 20 and 24]: Blood samples were collected at specified timepoints for the assessment of serum concentration of testosterone.

Sex: Male, ages: 18 Years to any

Inclusion Criteria :

* Participant is capable of giving signed informed consent
* Participant must be over 18 years of age, at the time of signing the informed consent.
* Has a histologically or cytologically confirmed adenocarcinoma, locally advanced or metastatic prostate cancer. Or participant has PSA recurrence after curative treatment and be a candidate for androgen deprivation therapy (ADT).
* Has serum testosterone level >150 ng/dL (> 5.2 nmol/L).
* Has expected survival time ≥12 months according to the investigator's assessment.
* Has Eastern Cooperative Oncology Group (ECOG) performance status score ≤1

Exclusion Criteria :

* Risk of a serious complication in the case of tumour flare
* Presence of another neoplastic lesion or brain metastases.
* Previous history of QT prolongation or concomitant use of medicinal products known to prolong the QT interval or with a known risk of torsades de pointes.
* Metastatic hormone-sensitive prostate cancer with high tumour burden.
* Metastatic castration-resistant prostate cancer.
* Previous surgical castration.
* Previous hormone therapy (including abiraterone) for prostate cancer within 6 months prior to study start.
* Previous cytotoxic chemotherapy treatment within 6 months prior to study screening.
* Use of finasteride or dutasteride within 2 months prior to study screening.
* Previous hypophysectomy or adrenalectomy
* Any current use or use within 6 months prior to treatment start of medications which are known to affect the metabolism and/or secretion of androgenic hormones: ketoconazole, aminoglutethimide, oestrogens and antiandrogens.
* Current use of systemic or inhaled corticosteroids (topical application permitted).
* Any previous use of traditional Chinese medicine or herbal products within 1 month prior to study screening or planned use during the study of products, which are known to have cytotoxic effect or affect the metabolism and/or secretion of androgenic hormones
* Participation in another study with an investigational drug or treatment within 3 months prior to study screening or within 5 drug half-lives of the investigational drug (whichever is the longer).
* Severe kidney or liver impairment (creatinine >2 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 x ULN).
* Any concomitant disorder or resulting therapy that is likely to interfere with participant compliance, the i.m. administration of the drug or with the study in the opinion of the investigator.
* Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH agonist/analogues.
* Known active use of recreational drug or alcohol dependence in the opinion of the investigator.

Participant flow

Outcome results

• Percentage of Participants Who Achieved Castrate Levels of Serum Testosterone on Day 29 (Primary), Number, percentage of participants: Triptorelin Pamoate 99.5 (97.1 to 100.0)
• Percentage of Participants Who Maintained the Castrate Levels From Week 8 to Week 24 (Primary), Number, percentage of participants: Triptorelin Pamoate 100 (98.1 to 100.0)
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Local Tolerance (Secondary), Count of participants, Participants: Triptorelin Pamoate 160
• Percent Change From Baseline in Prostate Specific Antigen (PSA) at Weeks 12 and 24 (Secondary), Mean, percent change: Triptorelin Pamoate -90.6815 +/- 10.8057
• Time to Maximum Observed Plasma Concentration (Tmax) of Triptorelin Pamoate (Secondary), Median, hour: Triptorelin Pamoate 2.95 (1.93 to 11.5)
• Maximum Observed Plasma Concentration (Cmax) of Triptorelin Pamoate (Secondary), Mean, ng/milliliter (mL): Triptorelin Pamoate 44.5 +/- 17.5
• Area Under the Plasma Concentration Time Curve From Time 0 to the Visit on Day 169 (AUC0-169) of Triptorelin Pamoate (Secondary), Mean, ng*day/mL: Triptorelin Pamoate 51.7 +/- 22.9
• Area Under the Plasma Concentration Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Triptorelin Pamoate (Secondary), Mean, ng*day/mL: Triptorelin Pamoate 46.3 +/- 22.1
• Time to Maximum Observed Plasma Concentration of Testosterone (Secondary), Median, day: Triptorelin Pamoate 2.00 (0 to 4.02)
• Maximum Observed Plasma Concentration of Testosterone (Secondary), Mean, nmol/L: Triptorelin Pamoate 21.9 +/- 6.55
• Time to Castration of Testosterone (Secondary), Median, day: Triptorelin Pamoate 19.3 (14.5 to 25.3)
• Plasma Concentrations of Triptorelin Pamoate (Secondary), Mean, ng/mL: Triptorelin Pamoate NA +/- NA
• Serum Concentrations of Testosterone (Secondary), Mean, nmol/L: Triptorelin Pamoate 17.0506 +/- 7.0323

Adverse events

Time frame: TEAEs are reported from the first dose of study intervention (Day 1) up to end of study visit (Week 24), approximately 169 days

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2024-03-18)
• Statistical Analysis Plan (PDF, 2024-09-24)

• Ipsen Medical, Director, Study director, Ipsen