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

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03232281
• Collaborator: (none)
• Enrollment: 300
• Locations: 24
• Arms: 2
• Actual Duration (Months): 27.6
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Triptorelin Pamoate PR 3-month; Drug: Triptorelin Acetate PR 1-month	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 28, 2017
• Actual Primary Completion Date: May 17, 2019
• Actual Study Completion Date: Nov 16, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Week 12 [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.

Secondary Outcome Measures

1. Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Weeks 4 and 8 [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.

2. Percentage of Subjects Castrated (E2 ≤110 Pmol/L or 30 pg/mL) at Weeks 4, 8 and 12 [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.

3. Change From Baseline in Endometriosis-associated Pelvic Pain at Weeks 4, 8 and 12 [Baseline (Day 1) and 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.

4. Mean E2 Concentration at Weeks Baseline and 4, 8 and 12 [Baseline (Day 1) and Weeks 4, 8 and 12]

   The mean serum E2 concentrations at baseline and Weeks 4, 8 and 12 are presented.

5. Mean Follicle Stimulating Hormone (FSH) Concentration at Baseline and Weeks 4, 8 and 12 [Baseline (Day 1) and Weeks 4, 8 and 12]

   The mean FSH concentrations at baseline and Weeks 4, 8 and 12 are presented.

6. Mean Luteinising Hormone (LH) Concentration at Baseline and Weeks 4, 8 and 12 [Baseline and Weeks 4, 8 and 12]

   The mean LH concentrations at baseline and Weeks 4, 8 and 12 are presented.

7. Median Time to Menses Recovery [Baseline (Day 1) up to Week 40 (end of study visit)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Obstetrics and Gynecology Hospital, Capital Medical University	Beijing		China	100006
2	Peking University First Hospital	Beijing		China	100034
3	Chinese PLA General Hospital	Beijing		China	100039
4	Peking University People's Hospital	Beijing		China	100044
5	Beijing Friendship Hospital, Capital Medical University	Beijing		China	100069
6	Peking University Third Hospital	Beijing		China	100191
7	Peking Union Medical College Hospital	Beijing		China	100730
8	The First Affiliated Hospital of Dalian Medical University	Dalian		China	116011
9	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China	510120
10	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou		China	510235
11	The Third Affiliated Hospital, Sun Yat-sen University	Guangzhou		China	510630
12	Hainan General Hospital	Haikou		China	570311
13	Women's Hospital, School of Medicine Zhejiang University	Hangzhou		China	310006
14	Sir Run Run Shaw Hospital school of medicine, Zhejiang University	Hangzhou		China	310020
15	Nanjing Maternity and Child Health Care Hospital	Nanjing		China	210004
16	Zhongda Hospital, Southeast University	Nanjing		China	210009
17	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning		China	530021
18	Obstetrics and Gynaecology Hospital of Fudan University	Shanghai		China	200011
19	Shanghai Tongji Hospital	Shanghai		China	200065
20	The Second Hospital of Hebei Medical University	Shijiazhuang		China	050000
21	Tianjin Medical University General Hospital	Tianjin		China	300052
22	The Second Hospital of Tianjin Medical University	Tianjin		China	300211
23	Northern Jiangsu People's Hospital	Yangzhou		China	225001
24	General Hospital of Ningxia Medical University	Yinchuan		China	750004

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Study Protocol - Sep 29, 2017
• Statistical Analysis Plan - Dec 13, 2019

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT03232281
• Other Study ID Numbers: D-CN-52014-220
• First Posted: Jul 27, 2017
• Last Update Posted: Oct 14, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Endometriosis; Triptorelin Pamoate

Study Results

Participant Flow

Recruitment Details	Female subjects aged from 18 to 45 years were recruited to this Phase 3 randomised, open-label study at 24 study centres in China between 28 July 2017 and 16 November 2019.
Pre-assignment Detail	Subjects who met the inclusion criteria and none of the exclusion criteria were randomised in a 1:1 ratio, stratified according to endometriotic surgical history and the severity of endometriosis-associated pelvic pain.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 milligrams (mg) triptorelin pamoate per injection, administered as an intramuscular (IM) injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Period Title: Overall Study
STARTED	150	150
Received Treatment	149	150
Completed Week 12	143	148
Completed Week 24	143	144
COMPLETED	143	144
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month	Total
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).	Total of all reporting groups
Overall Participants	150	150	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.4 (6.1)	32.6 (6.2)	32.5 (6.1)
Sex: Female, Male (Count of Participants)
Female	150 100%	150 100%	300 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Chinese	150 100%	150 100%	300 100%
Not Hispanic or Latino	150 100%	150 100%	300 100%
Region of Enrollment (participants) [Number]
China	150 100%	150 100%	300 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Week 12
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The per protocol set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter, and without major protocol violations/deviations affecting the primary efficacy endpoint.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	142	146
Number (95% Confidence Interval) [percentage of subjects]	98.6	99.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was confirmed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -4.41 to 2.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

2. Secondary Outcome

Title	Percentage of Subjects Castrated (E2 ≤184 Pmol/L or 50 pg/mL) at Weeks 4 and 8
Description	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.
Time Frame	Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Week 4	98.0	99.3
Week 8	97.3	100.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	Rate difference at Week 4. The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was observed without multiplicity adjustment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -5.26 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	Rate difference at Week 8. The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was observed without multiplicity adjustment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -6.80 to -0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

3. Secondary Outcome

Title	Percentage of Subjects Castrated (E2 ≤110 Pmol/L or 30 pg/mL) at Weeks 4, 8 and 12
Description	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.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Week 4	98.0	99.3
Week 8	95.2	99.3
Week 12	95.9	98.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	Rate difference at Week 4. The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was observed without multiplicity adjustment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -5.26 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	Rate difference at Week 8. The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was observed without multiplicity adjustment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -8.93 to -0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Triptorelin Pamoate PR 3-month, Triptorelin Acetate PR 1-month
	Comments	Rate difference at Week 12. The null hypothesis was that triptorelin pamoate PR 3-month was inferior to triptorelin acetate PR 1-month. The alternative hypothesis was that triptorelin pamoate PR 3-month was non-inferior to triptorelin acetate PR 1-month.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% CI for the difference was >-10%, triptorelin pamoate PR 3-month non-inferiority to triptorelin acetate PR 1-month was observed without multiplicity adjustment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate difference (%)
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -7.44 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	The rate difference (triptorelin pamoate PR 3-month - triptorelin acetate PR 1-month) and the 2-sided 95% CI of the difference were calculated using the Miettinen and Nurminen method, stratified by randomisation stratification factors.

4. Secondary Outcome

Title	Change From Baseline in Endometriosis-associated Pelvic Pain at Weeks 4, 8 and 12
Description	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.
Time Frame	Baseline (Day 1) and Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Week 4	-24.4	-24.4
Week 8	-28.5	-27.8
Week 12	-28.1	-28.4

5. Secondary Outcome

Title	Mean E2 Concentration at Weeks Baseline and 4, 8 and 12
Description	The mean serum E2 concentrations at baseline and Weeks 4, 8 and 12 are presented.
Time Frame	Baseline (Day 1) and Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Baseline	192.302 (258.209)	218.893 (296.825)
Week 4	25.347 (46.253)	18.959 (3.944)
Week 8	47.175 (156.521)	21.863 (12.550)
Week 12	36.600 (76.882)	26.695 (31.174)

6. Secondary Outcome

Title	Mean Follicle Stimulating Hormone (FSH) Concentration at Baseline and Weeks 4, 8 and 12
Description	The mean FSH concentrations at baseline and Weeks 4, 8 and 12 are presented.
Time Frame	Baseline (Day 1) and Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Baseline	6.099 (3.929)	6.258 (4.520)
Week 4	1.762 (1.373)	1.699 (1.049)
Week 8	2.891 (1.163)	2.766 (1.329)
Week 12	3.344 (1.347)	3.325 (1.414)

7. Secondary Outcome

Title	Mean Luteinising Hormone (LH) Concentration at Baseline and Weeks 4, 8 and 12
Description	The mean LH concentrations at baseline and Weeks 4, 8 and 12 are presented.
Time Frame	Baseline and Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Baseline	3.376 (1.902)	3.487 (1.858)
Week 4	0.660 (1.771)	0.500 (0.173)
Week 8	0.444 (1.928)	0.255 (0.122)
Week 12	0.324 (0.555)	0.251 (0.239)

8. Secondary Outcome

Title	Median Time to Menses Recovery
Description	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.
Time Frame	Baseline (Day 1) up to Week 40 (end of study visit)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomised subjects who received at least one dose of study medication with at least one baseline and at least one post-baseline assessment of the primary efficacy parameter.

Arm/Group Title	Triptorelin Pamoate PR 3-month	Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).	Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
Measure Participants	147	150
Median (95% Confidence Interval) [days]	179.0	85.0

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were monitored from Day 1 up to Week 28 (approximately 7 months).
Adverse Event Reporting Description	A TEAE was defined as any adverse event that occurred or worsened on or after the first dose, through 112 days (16 weeks) after last injection of triptorelin pamoate PR 3-month or through 56 days (8 weeks) after last injection for triptorelin acetate PR 1-month. TEAEs are presented for the safety set which included all subjects who received at least one dose of study medication.
Arm/Group Title	Triptorelin Pamoate PR 3-month		Triptorelin Acetate PR 1-month
Arm/Group Description	Subjects received 15 mg triptorelin pamoate per injection, administered as an IM injection once every 12 weeks (a total of 2 injections, at baseline and Week 12).		Subjects received 3.75 mg triptorelin acetate per injection, administered as an IM injection once every 4 weeks (a total of 6 injections, at baseline and Weeks 4, 8, 12, 16 and 20).
All Cause Mortality
	Triptorelin Pamoate PR 3-month		Triptorelin Acetate PR 1-month
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/149 (0%)		0/150 (0%)
Serious Adverse Events
	Triptorelin Pamoate PR 3-month		Triptorelin Acetate PR 1-month
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/149 (1.3%)		1/150 (0.7%)
Cardiac disorders
Arrhythmia	1/149 (0.7%)	1	0/150 (0%)	0
Sinus bradycardia	1/149 (0.7%)	1	0/150 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/149 (0%)	0	1/150 (0.7%)	1
Infections and infestations
Pyelonephritis acute	1/149 (0.7%)	1	0/150 (0%)	0
Sepsis	1/149 (0.7%)	1	0/150 (0%)	0
Other (Not Including Serious) Adverse Events
	Triptorelin Pamoate PR 3-month		Triptorelin Acetate PR 1-month
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	132/149 (88.6%)		135/150 (90%)
Gastrointestinal disorders
Abdominal pain lower	4/149 (2.7%)	4	13/150 (8.7%)	19
Abdominal pain upper	6/149 (4%)	7	8/150 (5.3%)	10
Diarrhoea	8/149 (5.4%)	8	4/150 (2.7%)	4
General disorders
Pyrexia	6/149 (4%)	6	8/150 (5.3%)	9
Infections and infestations
Nasopharyngitis	16/149 (10.7%)	19	24/150 (16%)	30
Upper respiratory tract infection	37/149 (24.8%)	46	27/150 (18%)	34
Vaginal infection	8/149 (5.4%)	9	7/150 (4.7%)	7
Investigations
Protein urine present	9/149 (6%)	9	8/150 (5.3%)	8
Musculoskeletal and connective tissue disorders
Arthralgia	12/149 (8.1%)	19	13/150 (8.7%)	15
Back pain	9/149 (6%)	11	9/150 (6%)	10
Pain in extremity	2/149 (1.3%)	3	9/150 (6%)	13
Nervous system disorders
Dizziness	6/149 (4%)	7	9/150 (6%)	11
Headache	10/149 (6.7%)	11	9/150 (6%)	11
Psychiatric disorders
Insomnia	14/149 (9.4%)	14	8/150 (5.3%)	8
Reproductive system and breast disorders
Menorrhagia	11/149 (7.4%)	13	6/150 (4%)	6
Vaginal haemorrhage	66/149 (44.3%)	79	68/150 (45.3%)	82
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	4/149 (2.7%)	4	8/150 (5.3%)	9
Skin and subcutaneous tissue disorders
Hyperhidrosis	10/149 (6.7%)	10	12/150 (8%)	12
Night sweats	19/149 (12.8%)	20	13/150 (8.7%)	13
Vascular disorders
Hot flush	86/149 (57.7%)	90	89/150 (59.3%)	91

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.