Efficacy and safety of a progestin and an aromatase inhibitor combined in a intravaginal ring in symptomatic endometriosis.

• Register: EUCTR
• Last refreshed on: 17 July 2017
• Main ID: EUCTR2013-005090-53-CZ
• Date of registration: 29/07/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Efficacy and safety of a progestin and an aromatase inhibitor combined in a intravaginal ring in symptomatic endometriosis.
• Scientific title: A randomized, double-blind, double-dummy, parallel- group, multi-center phase IIb study to assess the efficacy and safety of different dose combinations of an aromatase inhibitor and a progestin in an intravaginal ring versus placebo and leuprorelin / leuprolide acetate in women with symptomatic endometriosis over a 12-week treatment period - ESPARIOS 1
• Date of first enrolment: 05/11/2014
• Target sample size: 318
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005090-53
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Denmark, Finland, Germany, Italy, Japan, Netherlands, Norway, Poland, Spain, Switzerland, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed and dated informed consent.
2. Premenopausal women18 years and above at the time of screening.
3. Women with endometriosis confirmed by laparoscopy or laparotomy within the last ten years but not less than 8 weeks before the screening visit
In Japan, diagnosis based on imaging (transvaginal ultrasound or MRI) also qualifies for inclusion.
4. Moderate to severe endometriosis-associated pelvic pain (EAPP) of =5 in the last 28 days before screening visit 1 measured on the numeric rating scale (NRS; i.e. 4-week recall period).
5. At randomization: Adherence to the study procedures during the screening period, at least 24 diary entries of ESD item 1 during the last 28 consecutive days before the randomization visit, and a sum of the available ESD item 1 (‘worst pain’ on the daily NRS) entries during this period of at least 98 (corresponding to an average score of = 3.5).
6. Willingness to use only ibuprofen as rescue pain medication for EAPP, if needed according to investigator’s instruction.
7. Use of a non-hormonal barrier method (i.e. spermicide-coated condoms) for contraception from screening visit until the end of the study. This is not required if adequate contraception is achieved by vasectomy of the partner.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 318
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnancy or lactation (less than three months since delivery, abortion, or lactation before start of treatment)
2. Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug
3. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
4. Any disease or condition that may worsen under hormonal treatment according to the assessment and opinion of the investigator.
5. Undiagnosed abnormal genital bleeding
6. Wish for pregnancy during the study
7. Regular use of pain medication due to other underlying diseases
8. Non-responsiveness of endometriosis associated pelvic pain (EAPP) to GnRH-a or surgery (partial response is not exclusionary).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Endometriosis
MedDRA version: 19.0 Level: LLT Classification code 10014788 Term: Endometriosis related pain System Organ Class: 10038604 - Reproductive system and breast disorders
MedDRA version: 19.0 Level: PT Classification code 10014778 Term: Endometriosis System Organ Class: 10038604 - Reproductive system and breast disorders

Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

Intervention(s)

Product Name: Anastrozole +Levonorgestrel VDS, 50 mg + 170 mg
Product Code: BAY 98-7196
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: ANASTROZOLE
CAS Number: 120511-73-1
Current Sponsor code: BAY 1025096
Other descriptive name: ANASTROZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Levonorgestrel
CAS Number: 797-63-7
Current Sponsor code: ZK 00018206
Other descriptive name: LEVONORGESTREL MICRONISED
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 170-
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use

Product Name: Anastrozole +Levonorgestrel VDS 120 mg + 170 mg
Product Code: BAY 98-7196
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: ANASTROZOLE
CAS Number: 120511-73-1
Current Sponsor code: BAY 1025096
Other descriptive name: ANASTROZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
INN or Proposed INN: Levonorgestrel
CAS Number: 797-63-7
Current Sponsor code: ZK 00018206
Other descriptive name: LEVONORGESTREL MICRONISED
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 170-
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use
Pharmaceutical form of the placebo: Vaginal delivery system
Route of administration of the placebo: Vaginal use

Product Name: Anastrozole +Levonorgestrel VDS 200 mg + 170 mg
Product Code: BAY 98-7196
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: ANASTROZOLE
CAS Number: 120511-73-1
Current Sponsor code: BAY 1025096
Other descriptive name: ANASTROZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Levonorgestrel
CA

Primary Outcome(s)

Primary end point(s): The primary efficacy variable is the absolute change in mean pain of the 7 days with worst EAPP from baseline (last 28 days before randomization) to end of treatment (last 28 days of the treatment period, Day 57 - 84).

Secondary Objective: Secondary objectives of this study are
To identify at least 1 superior effective dose of BAY 98-7196 compared to placebo
To compare the efficacy of BAY 98-7196 vs leuprorelin / leuprolide acetate descriptively
To assess sustainability of treatment effect and recurrence of symptoms
To evaluate the safety and tolerability of BAY 98-7196 in women with symptomatic endometriosis
To explore sub-populations (e.g. subjects with indication for treatment with a gonadotropin-releasing hormone agonist or surgery as judged by the investigator or by endometriosis history and symptom severity)

Main Objective: To assess the dose-response relationship and demonstrate efficacy of BAY 98-7196 vs. placebo in women with symptomatic endometriosis.

Timepoint(s) of evaluation of this end point: Baseline (last 28 days before randomization) versus end of treatment (last 28 days of the treatment period, Day 57 – 84).

Secondary Outcome(s)

Secondary end point(s): Absolute change in mean pain of the 7 days with worst EAPP from baseline (last 28 days before randomization) to the first cycle under study treatment (Day 1 - 28) and to the second cycle under study treatment (Day 29 - 56).

Absolute change in mean pain from baseline (last 28 days before randomization) to the first cycle under study treatment (Day 1 - 28), the second cycle under study treatment (Day 29 - 56), and to the third cycle under study treatment (Day 57 - 84).

Number of days during baseline (last 28 days before randomization) and Cycles 1, 2, and 3 with pain = 7 (measured on the NRS by Question 1 of the ESD) and change from baseline.

Number of days during baseline (last 28 days before randomization) and Cycles 1, 2, and 3 with pain = 4 (measured on the NRS by Question 1 of the ESD) and change from baseline.

Timepoint(s) of evaluation of this end point: Baseline (last 28 days before randomization) vs the first cycle under study treatment (Day 1 - 28) and to the second cycle under study treatment (Day 29 - 56).

Baseline (last 28 days before randomization) vs the first cycle under study treatment (Day 1 - 28), the second cycle under study treatment (Day 29 - 56), and to the third cycle under study treatment (Day 57 - 84).

Baseline (last 28 days before randomization) and Cycles 1, 2, and 3.

Baseline (last 28 days before randomization) and Cycles 1, 2, and 3.

Secondary ID(s)

BAY98-7196/15832

2013-005090-53-FI

Source(s) of Monetary Support

Bayer AG