Study to Compare the Oestradiol Suppression, Clinical Efficacy and Safety of Two Formulations of Triptorelin (Triptorelin Pamoate PR 3-month and Triptorelin Acetate PR 1-month) in Chinese Subjects With Endometriosis

Study Overview
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Brief Summary
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To assess the efficacy of triptorelin pamoate prolonged release (PR) 3-month formulation in Chinese female subjects with endometriosis by demonstrating the non-inferiority of triptorelin pamoate PR 3-month formulation injected once as compared to triptorelin acetate PR 1-month formulation injected 3 times consecutively.

Official Title
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A Phase III, Multicentre, Randomised, Open-label, Parallel, Active-controlled Study to Compare the Oestradiol Suppression, Clinical Efficacy and Safety of Two Formulations of Triptorelin (Triptorelin Pamoate PR 3-month and Triptorelin Acetate PR 1-month) in Chinese Subjects With Endometriosis

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Triptorelin Pamoate PR 3-month
* Drug: Triptorelin Acetate PR 1-month


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects aged from 18 to 45 years inclusive at the date of informed consent. A history of active and regular menstrual cycles of 21 to 35 days (inclusive) in the 6 months prior to the screening visit. A diagnosis of endometriosis, confirmed by laparoscopy or laparotomy within10 years prior to the screening visit. Requires treatment with a Gonadotrophin releasing hormone (GnRH) agonist for a period of 6 months in the judgement of the investigator. Exclusion Criteria: A current history of undiagnosed abnormal genital bleeding. Received treatment with a GnRH agonist within 6 months prior to the screening visit. Received any other hormonal treatment within 3 months prior to the screening visit (oestrogens, progestogens, danazol, gestrinone and cyproterone acetate etc). Chronic pelvic pain that is not caused by endometriosis, that would interfere with the assessment of endometriosis-associated pelvic pain.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triptorelin pamoate PR 3-month<br>Subjects received 15 mg triptorelin pamoate per injection, administered as an intramuscular injection once every 12 weeks (a total of 2 injections, at baseline and Week 12). | Drug: Triptorelin Pamoate PR 3-month<br>* 15mg/injection, administered as an intramuscular injection once every 12 weeks (a total of 2 injections).<br>* Other names: Triptorelin pamoate for injection 15 mg;|
| Active Comparator: Triptorelin acetate PR 1-month<br>Subjects received 3.75 mg triptorelin acetate per injection, administered as an intramuscular injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20). | Drug: Triptorelin Acetate PR 1-month<br>* 3.75mg/injection, administered as an intramuscular injection once every 4 weeks (a total of 6 injections)<br>* Other names: Diphereline 3.75 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Week 12 | Castration was defined as serum oestradiol (E2) ≤184 picomoles/litre (pmol/L) or 50 picograms/millilitre (pg/mL). The primary endpoint was evaluated based on centralised blinded bioanalysis of serum samples for E2. The percentage of subjects castrated and the 95% asymptotic confidence intervals (CIs), calculated from binomial distribution, are presented. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Weeks 4 and 8 | The percentages of subjects who were castrated at Weeks 4 and 8 where castration was defined as serum E2 ≤184 pmol/L or 50 pg/mL are presented. The 95% asymptotic CIs were calculated from the binomial distribution. | Weeks 4 and 8 | 
| Percentage of Subjects Castrated (E2 ≤110 Pmol/L or 30 pg/mL) at Weeks 4, 8 and 12 | The percentages of subjects who were castrated at Weeks 4, 8 and 12 where castration was defined as serum E2 ≤110 pmol/L or 30 pg/mL are presented. The 95% asymptotic CIs were calculated from the binomial distribution. | Weeks 4, 8 and 12 | 
| Change From Baseline in Endometriosis-associated Pelvic Pain at Weeks 4, 8 and 12 | Endometriosis-associated pelvic pain was assessed using a 100 millimetres (mm) visual analogue scale (VAS) where subjects indicated the subjective level of their most severe endometriosis pain over the last 4 weeks by making a single vertical mark on the line ranging from 'absence of pain' (0 mm) to 'unbearable pain' (100 mm). Lower scores indicated a better outcome. Baseline was defined as the last available assessment prior to the first dose of study medication. The least squares (LS) mean change from baseline at each timepoint as measured by the VAS is presented. | Baseline (Day 1) and Weeks 4, 8 and 12 | 
| Mean E2 Concentration at Weeks Baseline and 4, 8 and 12 | The mean serum E2 concentrations at baseline and Weeks 4, 8 and 12 are presented. | Baseline (Day 1) and Weeks 4, 8 and 12 | 
| Mean Follicle Stimulating Hormone (FSH) Concentration at Baseline and Weeks 4, 8 and 12 | The mean FSH concentrations at baseline and Weeks 4, 8 and 12 are presented. | Baseline (Day 1) and Weeks 4, 8 and 12 | 
| Mean Luteinising Hormone (LH) Concentration at Baseline and Weeks 4, 8 and 12 | The mean LH concentrations at baseline and Weeks 4, 8 and 12 are presented. | Baseline and Weeks 4, 8 and 12 | 
| Median Time to Menses Recovery | Time to menses recovery was defined as the time (in days) between the date of the last dose of study medication and the date of the first day the subject observed menstrual bleeding of the next menstrual period. Menses recovery status was assessed at all study visits from Day 1 to the end of study visit. The median time to menses recovery was analysed using the Kaplan-Meier method. | Baseline (Day 1) up to Week 40 (end of study visit) |