Trial · Interventional

CompletedPhase 2Results postedRegistry data

Bay98-7196, Dose Finding / POC Study

NCTNCT02203331Other id15832Other id2013-005090-53

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Overview

Status: Completed
Phase: Phase 2
Enrollment: 319 participants (actual)
Sponsor: Bayer · Industry
Design: Randomized · Triple masking
Countries: 14 countries
United States, Austria, Belgium, Canada, Czechia, Denmark, Finland, Germany, Japan, Netherlands, Norway, Poland, Spain, Switzerland
Start: 16 Oct 2014
Primary completion: 24 Oct 2016
Completion: 24 Oct 2016
First posted: 29 Jul 2014 (estimated)
Last update posted: 7 Nov 2023
Conditions: Endometriosis

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2014201520162017

Ph 2
Bay98-7196, Dose Finding / POC Study
NCT02203331
16 Oct 2014 to 24 Oct 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

PlaceboDrug
LevonorgestrelDrug
AnastrozoleDrug
Lupron / Leuprolide acetateDrug

Arms6

Placebo comparator
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
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
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
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
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

Primary outcomes1

Outcomes the sponsor listed as primary.

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
Time frame · Baseline (last 28 days before randomization), end of treatment (Treatment 3) (last 28 days of the treatment period, Day 57-84)
Registry description
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.

Secondary outcomes(6)

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
Time frame · Baseline (last 28 days before randomization), first cycle (Treatment 1) (Day 1-28), second cycle (Treatment 2) (Day 29-56)
Registry description
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.
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
Time frame · 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)
Registry description
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.
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
Time frame · Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Registry description
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.
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
Time frame · Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Registry description
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.
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
Time frame · Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Registry description
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.
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
Time frame · Baseline (last 28 days before randomization), Cycle 1 (Treatment 1), Cycle 2 (Treatment 2), and Cycle 3 (Treatment 3)
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (last 28 days before randomization), end of treatment (Treatment 3) (last 28 days of the treatment period, Day 57-84)

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

Group	Value (units on a scale)	Spread
LNG 40 mcg IVR + Placebo Injection	-1.8974	1.6416
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	-1.6061	1.6652
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	-2.4014	2.1833
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	-2.2653	1.5972
Placebo IVR + Leuprorelin Injection	-3.7679	2.3507
Placebo IVR + Placebo Injection	-2.293	1.8247

Secondary and other outcome results(6)

Secondary outcomeMean· 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 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

Group	Value (units on a scale)	Spread
LNG 40 mcg IVR + Placebo Injection	-0.7582	1.1518
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	-0.6849	1.3832
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	-1.1463	1.3992
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	-1.0000	1.2579
Placebo IVR + Leuprorelin Injection	-1.2071	1.1978
Placebo IVR + Placebo Injection	-0.9048	1.1686

Secondary outcomeMean· 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)

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

Group	Value (units on a scale)	Spread
LNG 40 mcg IVR + Placebo Injection	6.0938	1.5314
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	5.7409	1.3044
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	6.3694	1.5300
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	5.7128	1.4415
Placebo IVR + Leuprorelin Injection	6.3962	1.4575
Placebo IVR + Placebo Injection	5.6399	1.5312

Secondary outcomeMean· 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 Greater Than or Equal to (>=) 7 as Measured on NRS by Question 1 of ESD as Measured on NRS by Question 1 of ESD

Group	Value (percentage of days)	Spread
LNG 40 mcg IVR + Placebo Injection	35.6034	34.3126
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	27.5659	27.6426
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	40.0813	37.2694
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	23.9322	28.6234
Placebo IVR + Leuprorelin Injection	28.2015	28.8430
Placebo IVR + Placebo Injection	25.1742	24.2811

Secondary outcomeMean· 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

Group	Value (percentage of days)	Spread
LNG 40 mcg IVR + Placebo Injection	-13.6756	22.6822
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	-12.5862	21.4336
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	-15.0341	21.0071
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	-13.3722	19.6416
Placebo IVR + Leuprorelin Injection	-19.8898	25.9273
Placebo IVR + Placebo Injection	-16.0105	19.0190

Secondary outcomeMean· 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

Group	Value (percentage of days)	Spread
LNG 40 mcg IVR + Placebo Injection	71.8037	32.3658
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	69.3092	27.8642
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	73.8956	31.6868
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	70.6504	27.8528
Placebo IVR + Leuprorelin Injection	70.2066	28.9333
Placebo IVR + Placebo Injection	65.9074	30.0166

Secondary outcomeMean· 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

Group	Value (percentage of days)	Spread
LNG 40 mcg IVR + Placebo Injection	-12.8228	20.4330
ATZ 300 mcg / LNG 40 mcg IVR + Placebo Injection	-15.4147	24.0608
ATZ 600 mcg / LNG 40 mcg IVR + Placebo Injection	-15.1334	22.5347
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo Injection	-15.1947	21.1740
Placebo IVR + Leuprorelin Injection	-21.4331	23.4546
Placebo IVR + Placebo Injection	-14.5323	20.9670

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
LNG 40 mcg IVR + Placebo InjectionParticipants wore an intra-vaginal ring (IVR) of Levonorgestrel (LNG) 40 microgram (mcg) continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of placebo matched to leuprorelin intramuscular (i.m.) injection (3 month depot) on the first day of study treatment.	–	2 / 49	38 / 49
ATZ 300 mcg / LNG 40 mcg IVR + Placebo InjectionParticipants wore IVR of Anastrozole (ATZ) 300 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.	–	0 / 50	40 / 50
ATZ 600 mcg / LNG 40 mcg IVR + Placebo InjectionParticipants wore IVR of ATZ 600 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.	–	0 / 54	40 / 54
ATZ 1050 mcg / LNG 40 mcg IVR + Placebo InjectionParticipants wore IVR of ATZ 1050 mcg and LNG 40 mcg (BAY98-7196) continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.	–	2 / 49	35 / 49
Placebo IVR + Leuprorelin InjectionParticipants wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of 11.25 milligram (mg) leuprorelin i.m. injection (3 month depot) on the first day of study treatment.	–	3 / 50	35 / 50
Placebo IVR + Placebo InjectionParticipants wore IVR of placebo matched to BAY98-7196 continuously for 84 days, with exchange of the IVR every 28 days and participants were administered a single dose of placebo matched to leuprorelin i.m. injection (3 month depot) on the first day of study treatment.	–	4 / 53	38 / 53

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: Female
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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).

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