Bay98-7196, Dose Finding / POC Study

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

Purpose of the study is to test efficacy and safety of BAY98-7196 intravaginal ring as a new treatment option for patients with endometriosis-associated pelvic pain

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Placebo; Drug: Levonorgestrel; Drug: Anastrozole; Drug: Lupron / Leuprolide acetate

• Study Type: Interventional
• Enrollment (Actual): 319
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
  • Kärnten
    • Villach, Kärnten, Austria, 9500
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
• Belgium
  • Bruxelles - Brussel, Belgium, 1070
  • Bruxelles - Brussel, Belgium, 1000
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
• Canada
  • Quebec, Canada, G1S 2L6
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
    • Ottawa, Ontario, Canada, K1H 7W9
    • Toronto, Ontario, Canada, M5C 2T2
  • Quebec
    • Montreal, Quebec, Canada, H4P 2S4
• Czechia
  • Brno, Czechia, 625 00
  • Brno, Czechia, 602 00
  • Ceske Budejovice, Czechia, 37001
  • Hradec Kralove, Czechia, 500 03
  • Olomouc, Czechia, 772 00
  • Pisek, Czechia, 39701
  • Plzen, Czechia, 326 00
  • Praha 2, Czechia
  • Tabor, Czechia, 39003
• Denmark
  • Aarhus N, Denmark, 8200
  • Copenhagen, Denmark, 2100
  • Odense C, Denmark, DK-5000
• Finland
  • Espoo, Finland, 02100
  • Helsinki, Finland, 00510
  • Hyvinkää, Finland, 05850
  • Jyväskylä, Finland, 40100
  • Kuopio, Finland, 70100
  • Oulu, Finland, 90100
  • Turku, Finland, 20520
• Germany
  • Berlin, Germany, 12200
  • Berlin, Germany, 10787
  • Hamburg, Germany, 20357
  • Hamburg, Germany, 22587
  • Baden-Württemberg
    • Karlsruhe, Baden-Württemberg, Germany, 76199
    • Mannheim, Baden-Württemberg, Germany, 68165
  • Bayern
    • Erlangen, Bayern, Germany, 91054
    • München, Bayern, Germany, 81675
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
    • Köln, Nordrhein-Westfalen, Germany, 50931
  • Sachsen
    • Dippoldiswalde, Sachsen, Germany, 01744
    • Dresden, Sachsen, Germany, 01307
  • Sachsen-Anhalt
    • Bernburg, Sachsen-Anhalt, Germany, 06406
    • Blankenburg, Sachsen-Anhalt, Germany, 38889
  • Thüringen
    • Jena, Thüringen, Germany, 07743
• Japan
  • Kumamoto, Japan, 861-8520
  • Nagano, Japan, 381-8551
  • Osaka, Japan, 543-0023
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 800-0296
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0061
    • Sapporo, Hokkaido, Japan, 006-8555
    • Sapporo, Hokkaido, Japan, 060-0031
    • Sapporo, Hokkaido, Japan, 060-0807
  • Hyogo
    • Kawanishi, Hyogo, Japan, 666-0125
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8530
  • Okayama
    • Kurashiki, Okayama, Japan, 710-0824
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-0929
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
    • Minatoku, Tokyo, Japan, 107-0052
    • Shinagawa-ku, Tokyo, Japan, 141-8625
• Netherlands
  • Almere, Netherlands
  • Groningen, Netherlands, 9700 RB
  • Nieuwegein, Netherlands, 3435 CM
  • Zwolle, Netherlands, 8025 AB
• Norway
  • Asker, Norway, 1383
  • Stokmarknes, Norway, 8450
  • Tromsø, Norway, 9019
  • Trondheim, Norway, 7006
  • Tønsberg, Norway, 3111
• Poland
  • Bialystok, Poland, 15- 224
  • Katowice, Poland, 40-724
  • Krakow, Poland, 31-121
  • Leczna, Poland, 21-010
  • Lodz, Poland, 90-602
  • Lublin, Poland, 20-632
  • Szczecin, Poland, 71-434
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 8036
  • Sevilla, Spain, 41014
  • Valencia, Spain, 46014
  • Valencia, Spain, 46010
  • Madrid
    • Aravaca, Madrid, Spain, 28023
    • Collado Villalba, Madrid, Spain, 28400
    • Pozuelo de Alarcón, Madrid, Spain, 28223
  • Álava
    • Vitoria, Álava, Spain, 01009
• Switzerland
  • Bern, Switzerland, 3010
  • Frauenklinik, Switzerland
  • Luzern, Switzerland, 6000
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
• United States
  • California
    • San Diego, California, United States, 92108
    • San Francisco, California, United States, 94158-2509
  • Florida
    • Gainesville, Florida, United States, 32605
    • New Port Richey, Florida, United States, 34652
  • Georgia
    • Atlanta, Georgia, United States, 30338
    • Sandy Springs, Georgia, United States, 30328
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Palos Heights, Illinois, United States, 60463
  • Kansas
    • Wichita, Kansas, United States, 67226
  • Louisiana
    • Marrero, Louisiana, United States, 70072
  • Michigan
    • Canton, Michigan, United States, 48187
    • Detroit, Michigan, United States, 48034
    • Saginaw, Michigan, United States, 48604
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • New Jersey
    • Neptune, New Jersey, United States, 07754
    • Plainsboro, New Jersey, United States, 08536
  • North Carolina
    • Durham, North Carolina, United States, 27713
    • Greensboro, North Carolina, United States, 27408
    • Winston-Salem, North Carolina, United States, 27103
  • Ohio
    • Columbus, Ohio, United States, 43213
    • Dayton, Ohio, United States, 45409
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
  • Washington
    • Seattle, Washington, United States, 98105
  • Wisconsin
    • Madison, Wisconsin, United States, 53562

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Premenopausal women18 years and above at the time of screening.
• 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.
• 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).
• 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).
• Willingness to use only ibuprofen as rescue pain medication for EAPP, if needed according to investigator's instruction.
• 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

Exclusion Criteria:

• Pregnancy or lactation (less than three months since delivery, abortion, or lactation before start of treatment)
• 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
• Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
• Any disease or condition that may worsen under hormonal treatment according to the assessment and opinion of the investigator.
• Undiagnosed abnormal genital bleeding
• Wish for pregnancy during the study
• Regular use of pain medication due to other underlying diseases
• Non-responsiveness of endometriosis associated pelvic pain (EAPP) to GnRH-a or surgery (partial response is not exclusionary).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
Experimental: Levonorgestrel; Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection; Drug: Levonorgestrel; Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
Experimental: Anastrozole 300 µg/d + Levonorgestrel; Anastrozole 300 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection; Drug: Anastrozole; Participants received Anastrozole 300 µg/d or 600 µg/d or 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
Experimental: Anastrozole 600 µg/d + Levonorgestrel; Anastrozole 600 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection; Drug: Anastrozole; Participants received Anastrozole 300 µg/d or 600 µg/d or 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
Experimental: Anastrozole 1050 µg/d + Levonorgestrel; Anastrozole 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection; Drug: Anastrozole; Participants received Anastrozole 300 µg/d or 600 µg/d or 1050 µg/d + Levonorgestrel 40 µg/d intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection
Active Comparator: Lupron / Leuprolide acetate; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Lupron / Leuprolide acetate 11.25 mg 3-months depot intramuscular injection	Drug: Placebo; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Placebo 3-months depot intramuscular injection; Drug: Lupron / Leuprolide acetate; Placebo intravaginal ring (treatment for 84 days, 28 days wearing period for each ring) and Lupron / Leuprolide acetate 11.25 mg 3-months depot intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Treatment Period, Days 57-84) as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, participants were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7.	Baseline (last 28 days before randomization), end of treatment (Treatment 3) (last 28 days of the treatment period, Day 57-84)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Mean Pain of the 7 Days With Worst EAPP From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment (Day 1-28) and to Second Cycle Under Study Treatment (Day 29-56) as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain of the 7 days with worst EAPP within a 28-day window was calculated as the sum of ESD item 1 on 7 days with worst EAPP within that 28-day window divided by 7.	Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56)
Absolute Change in Mean Pain From Baseline (Last 28 Days Before Randomization) to First Cycle Under Study Treatment(Day1-28), Second Cycle Under Study Treatment(Day29-56),Third Cycle Under Study Treatment (Day57-84) as Measured on NRS by Question1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The mean pain within a 28-day window was calculated as the sum of ESD item 1 within that 28-day window divided by the number with non-missing days within that 28-day window. Here, number of subjects 'n' signifies evaluable subjects for the respective category.	Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56), and third cycle (Treatment 3) (last 28 days of the treatment period, Day 57-84)
Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain Greater Than or Equal to (>=) 7 as Measured on NRS by Question 1 of ESD as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=7 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that 28-day window where item 1 of the ESD was >=7.	Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=7 as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=7 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that 28-day window where item 1 of the ESD was >=7. Here, number of subjects 'n' signifies evaluable subjects for the respective category.	Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Percentage of Days During Baseline (Last 28 Days Before Randomization) and Cycles 1, 2, and 3 With Pain >=4 as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=4 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that window where Item 1 of the ESD was >=4. Here, number of subjects 'n' signifies evaluable subjects for the respective category.	Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Change From Baseline (Last 28 Days Before Randomization) to Cycle 1, 2, and 3 in Percentage of Days With Pain >=4 as Measured on NRS by Question 1 of ESD	Pain intensity was assessed on 11-point (0-10) NRS by question 1. In question 1, subjects were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The percentage of days with pain >=4 within a 28-day window was calculated as 100 divided by the number of non-missing days within that 28-day window multiplied by the number of days within that window where Item 1 of the ESD was >=4. Here, number of subjects 'n' signifies evaluable subjects for the respective category.	Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer AG products conducted in Europe.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2014
• Primary Completion (Actual): October 24, 2016
• Study Completion (Actual): October 24, 2016

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (Estimated): July 29, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Contraceptives, Oral, Synthetic; Leuprolide; Levonorgestrel; Anastrozole
• Other Study ID Numbers: 15832; 2013-005090-53 (EudraCT Number)