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

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

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.

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Triptorelin Pamoate PR 3-month; Drug: Triptorelin Acetate PR 1-month

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100039
    • Chinese PLA General Hospital
  • Beijing, China, 100006
    • Beijing Obstetrics and Gynecology Hospital, Capital Medical University
  • Beijing, China, 100069
    • Beijing Friendship Hospital, Capital Medical University
  • Dalian, China, 116011
    • The First Affiliated Hospital of Dalian Medical University
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University
  • Guangzhou, China, 510235
    • Sun Yat-sen Memorial Hospital, Sun Yat-Sen University
  • Guangzhou, China, 510630
    • The Third Affiliated Hospital, Sun Yat-Sen University
  • Haikou, China, 570311
    • Hainan General Hospital
  • Hangzhou, China, 310006
    • Women's Hospital, School of Medicine Zhejiang University
  • Hangzhou, China, 310020
    • Sir Run Run Shaw Hospital School of Medicine, Zhejiang University
  • Nanjing, China, 210004
    • Nanjing Maternity and Child Health Care Hospital
  • Nanjing, China, 210009
    • Zhongda Hospital, Southeast University
  • Nanning, China, 530021
    • The people's hospital of Guangxi Zhuang Autonomous Region
  • Shanghai, China, 200065
    • Shanghai Tongji Hospital
  • Shanghai, China, 200011
    • Obstetrics and Gynaecology Hospital of Fudan University
  • Shijiazhuang, China, 050000
    • The second hospital of Hebei Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Tianjin, China, 300211
    • The Second Hospital of Tianjin Medical University
  • Yangzhou, China, 225001
    • Northern Jiangsu People's Hospital
  • Yinchuan, China, 750004
    • General Hospital of Ningxia Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triptorelin pamoate PR 3-month; 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; 15mg/injection, administered as an intramuscular injection once every 12 weeks (a total of 2 injections).; Other Names: Triptorelin pamoate for injection 15 mg
Active Comparator: Triptorelin acetate PR 1-month; 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; 3.75mg/injection, administered as an intramuscular injection once every 4 weeks (a total of 6 injections); Other Names: Diphereline 3.75 mg

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Li X, Li H, Shi H, Li X, Zhou R, Lu D, Cai Y, Zhou Y, Cabri P, Shi X, Pedret-Dunn A, Leng J. Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial. Adv Ther. 2022 Oct;39(10):4663-4677. doi: 10.1007/s12325-022-02264-5. Epub 2022 Aug 10.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2017
• Primary Completion (Actual): May 17, 2019
• Study Completion (Actual): November 16, 2019

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 14, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: D-CN-52014-220

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No