Clinical trial NCT04614246: Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb
Official title: A Randomized, Double-blind, Open for Active Comparator, Parallel-group, Multicenter Phase 2b Study to Assess the Efficacy and Safety of Three Different Doses of P2X3 Antagonist (BAY1817080) Versus Placebo and Elagolix 150 mg in Women With Symptomatic Endometriosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Endometriosis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-11-03
Enrollment: 215
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess safety and efficacy of BAY 1817080 compared to elagolix and placebo in women with symptomatic endometriosis. Study details include:

* Study duration: 155 up to 285 days
* Treatment duration: 84 days
* Visit frequency: 3 laboratory every 2 weeks for participants on BAY 1817080 or placebo


Eligibility criteria: Inclusion Criteria:

* Participant must be ≥ 18 years of age at the time of signing the informed consent
* Visually-confirmed endometriosis: detection of endometriotic lesions during laparoscopy or laparotomy (with or without pathological diagnosis) within 10 years but no less than 8 weeks from Visit 1a (surgically diagnosed endometriosis). For Japan only and limited to no more than half of all randomized Japanese participants: the diagnosis can be based on previous imaging (i.e. endometriosis lesion detected by ultrasound or MRI). If the participant was diagnosed by ultrasound, the lesion must be visualized again by ultrasound at the screening visit. If the participant was diagnosed by MRI, the diagnosis must have been made within 12 months before Visit 1a (clinically diagnosed endometriosis).
* Both sub-criteria regarding pain symptoms must be fulfilled:

  * At Visit 1a, participant presents self-reported moderate to severe pain which - based on the judgement of the investigator - carries a reasonable likelihood to translate into a severity of pain symptoms sufficient to fulfil the eligibility criterion and be caused by endometriosis, and
  * During the screening period at least 24 daily ESD entries during the 28 consecutive days starting on the first day with menstrual bleeding at or after Visit 1a and entries in the ESD item 1a ('worst pain' on the daily numerical rating scale) sum up to 98 or more.
* Willingness to use standardized rescue pain medications for EAPP (i.e. ibuprofen, acetaminophen and tramadol) and not use any prophylactic pain medication, according to investigator's instruction
* Ability to swallow the study intervention, i.e., the different kinds of tablets, as complete units
* Good general health (except for findings related to endometriosis) as proven by medical history, physical and gynecological examinations and laboratory test results
* Normal or clinically insignificant cervical cytology not requiring further follow-up:

  * A cervical cytology sample has to be obtained during screening, or
  * A documented normal result has to be available from cervical cytology conducted within 12 months prior to Visit 1a.
  * Human papilloma virus (HPV) testing in participants with atypical squamous cells of unknown significance (ASCUS) will be used as an adjunctive test automatically. Participants with ASCUS can be included if they are negative for high-risk HPV strains.

Exclusion Criteria:

* Current pregnancy or less than 3 months since delivery, abortion or stop of lactation before Visit 1a
* Hypersensitivity to any ingredient of the study intervention and/or the standardized rescue medications
* Known osteoporosis
* History of a low trauma fracture
* Contraindications for elagolix or the standardized rescue medications
* Current malignancy or history of cancer (exception: basal cell or squamous cell carcinoma of the skin) within the last 5 years prior to Visit 1a
* Any other diseases or conditions that according to the investigator can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study intervention (e.g. extremely low body weight, chronic bowel disease, Crohn's disease and ulcerative colitis)
* Menopause or signs of menopausal transition, such as absence of regular menstrual cycles based on investigator's judgment (absence of information regarding menstrual bleeding pattern e.g. due to long term use of hormonal contraception is not an exclusion criterion)
* Any disease or condition that may worsen during the study period according to the assessment and opinion of the investigator
* Abnormal uterine bleeding in terms of regularity or heaviness (with the exception of heavy menstrual bleeding that does not require treatment)
* Any findings that require further diagnostic procedures to avoid harm to the participant (e.g. ovarian tumors of uncertain origin or pelvic masses of unclear etiology)
* Any serious or unstable diseases or medical conditions, including psychiatric disorders, that might interfere with the conduct of the study or the interpretation of the result, including for example:

  * history of hysterectomy and/or bilateral oophorectomy
  * any conditions considered to contribute significantly to pelvic pain by the investigator, e.g. fibromyalgia, uterine fibroids, irritable bowel syndrome or other bowel disorders
  * any other underlying diseases requiring regular use of pain medication (e.g. migraine)
  * history of or current anxiety or depression unless stable with or without medical treatment ≥ 6 months before Visit 1a
* Major surgery scheduled during the study period
* Non-responsiveness of EAPP to earlier treatment with GnRH-agonists or GnRH-antagonists, based on the judgement of the investigator
* SARS-CoV-2- positive virus RNA test within 4 weeks prior to Visit 1a reported by participant, regardless of whether the participant had symptoms
* History of COVID-19 infection with persistent/ongoing symptoms
* Contact with SARS-CoV-2- positive or COVID-19 patient within the last 4 weeks prior to Visit 1a
* Intake of medication prohibited due to potential drug-drug interaction
* Use of other treatments that might interfere with the conduct of the study or the interpretation of the results, including:

  * hormonal medications
  * other treatments intended for endometriosis/pelvic pain during participation in the study, including the use of herbal products or traditional Chinese medicine for symptom relief, with the exception of the standardized rescue pain medications
* Simultaneous participation in another clinical trial with investigational medicinal product(s). Participation in another trial 3 months prior to Visit 1a that might have an impact on the study objectives, at the discretion of the investigator
* Previous assignment to study intervention (randomization) in this study (allowing previously randomized participants to be re-included into the study may lead to bias)
* Laboratory values outside the inclusion range (specified in the laboratory manual) and considered clinically relevant

Primary outcomes:
measure: Absolute Change in Mean Worst Endometriosis Associated Pelvic Pain (EAPP), Primary Per Protocol Set (pPPS)
timeFrame: change from baseline to week 12
Secondary outcomes:
measure: Least Squares Mean (SE) Changes in Worst EAPP From Baseline to Week 12, Per Protocol Set
timeFrame: change from baseline to week 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: up to 14 days after the last study medication intake
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research Sites - Cahaba Medical Care
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Mobile Ob-Gyn, PC
state: Alabama
city: Phoenix
country: United States
facility: Precision Trials, AZ, LLC
state: Arizona
city: Encinitas
country: United States
facility: Diagnamics, Inc.
state: California
city: San Diego
country: United States
facility: West Coast OB/GYN Associates
state: California
city: Greenwood Village
country: United States
facility: Advanced Women's Health Institute
state: Colorado
city: Washington
country: United States
facility: Office of Dr. James A. Simon, MD
state: District of Columbia
city: Boynton Beach
country: United States
facility: Helix Biomedics, LLC
state: Florida
city: Fort Myers
country: United States
facility: Alliance for Multispecialty Research, LLC - Fort Meyers
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research Center, Inc.
state: Florida
city: Orange City
country: United States
facility: A Premier Medical Research of Florida, LLC
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Medisense, Inc.
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: College Park
country: United States
facility: Paramount Research Solutions-College Park
state: Georgia
city: Snellville
country: United States
facility: Journey Medical Research
state: Georgia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Metairie
country: United States
facility: Southern Clinical Research Associates LLC
state: Louisiana
city: Towson
country: United States
facility: Continental Clinical Solutions, LLC
state: Maryland
city: Detroit
country: United States
facility: Wayne State University Physicians Group
state: Michigan
city: Las Vegas
country: United States
facility: Essential Women's Health Associates
state: Nevada
city: Albuquerque
country: United States
facility: Bosque Womens Care
state: New Mexico
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Durham
country: United States
facility: Carolina Women's Research & Wellness Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Beavercreek
country: United States
facility: Clinical Inquest Center, Ltd.
state: Ohio
city: Dublin
country: United States
facility: Aventiv Research - Dublin
state: Ohio
city: Dublin
country: United States
facility: Centricity Research formerly Aventiv - Dublin
state: Ohio
city: Englewood
country: United States
facility: HWC Women's Research Center
state: Ohio
city: Mayfield Heights
country: United States
facility: University Hospitals Landerbrook Health Center
state: Ohio
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research, LLC
state: Tennessee
city: Chattanooga
country: United States
facility: ClinSearch, LLC
state: Tennessee
city: Memphis
country: United States
facility: Medical Research Center of Memphis, LLC
state: Tennessee
city: Murfreesboro
country: United States
facility: International Clinical Research-Tennessee LLC.
state: Tennessee
city: Dallas
country: United States
facility: Discovery Clinical Trials - Dallas
state: Texas
city: Houston
country: United States
facility: UT Health Women's Research Center at Memorial City
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Pearland
country: United States
facility: Advances in Health
state: Texas
city: Norfolk
country: United States
facility: Tidewater Clinical Research, Inc.
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School | OB/GYN Clinical Research Center
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: North Chesterfield
country: United States
facility: Virginia Physicians For Women
state: Virginia
city: Seattle
country: United States
facility: Seattle Clinical Research Center
state: Washington
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Gent
country: Belgium
facility: AZ Jan Palfijn Gent
state: Oost-Vlaanderen
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Gent
country: Belgium
facility: UZ Gent
city: Dupnitza
country: Bulgaria
facility: MC Asklepii OOD
city: Sofia
country: Bulgaria
facility: Spec. Hospital for Active Treatment of Oncological Diseases
city: Sofia
country: Bulgaria
facility: Medical Center Panaceya
city: Stara Zagora
country: Bulgaria
facility: MHAT Niamed
city: Varna
country: Bulgaria
facility: SHOGAT Prof Dimitar Stamatov
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital | The Ottawa Hospital Research Institute - Neurology - Ottawa Stroke Program
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Clinique OVO
state: Quebec
city: Quebec
country: Canada
facility: Alpha Recherche Clinique LB9
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
state: Guangdong
city: Wuhan
country: China
facility: Wuhan Tongji Reproductive Medicine Hospital
state: Hubei
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical university
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical university
state: Jiangsu
city: Hangzhou
country: China
facility: Women's Hospital School of Medicine Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital,Capital Med.Uni.
city: Beijing
country: China
facility: Peking University First Hospital
city: Brno - stred
country: Czechia
facility: Gynekologie Meda s.r.o. - Lidicka
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ceske Budejovice
country: Czechia
facility: GYN-MIKA s.r.o.
city: Pisek
country: Czechia
facility: Centrum gynekologicke rehabilitace
city: Plzen
country: Czechia
facility: GynCare MUDr. Michael Svec s.r.o.
city: Praha 5
country: Czechia
facility: GYNERA
city: Praha 6
country: Czechia
facility: Gynekologie Studentsky dum s.r.o.
city: Praha 8
country: Czechia
facility: Fakultní nemocnice Bulovka
city: Tabor
country: Czechia
facility: Dr. Smrhova-Kovacs
city: Parnu
country: Estonia
facility: Parnu Hospital
city: Tartu
country: Estonia
facility: Clinic Elite
city: Helsinki
country: Finland
facility: HUS / Naistenklinikka
city: Oulu
country: Finland
facility: Lääkärikeskus Gyneko
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Mannheim
country: Germany
facility: Praxisklinik am Rosengarten
state: Baden-Württemberg
city: Bernburg
country: Germany
facility: Praxis f. Gynäkologie und Geburtshilfe
state: Sachsen-Anhalt
city: Berlin
country: Germany
facility: emovis GmbH
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum (CVK)
city: Athens
country: Greece
facility: ARETAIEION University Hospital
city: Patra
country: Greece
facility: University General Hospital of Patras | Univ Obs & Gynae Cli
city: Budapest
country: Hungary
facility: Cortex Study Center
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Varese
country: Italy
facility: ASST Sette Laghi
state: Lombardia
city: Firenze
country: Italy
facility: A.O.U. Careggi
state: Toscana
city: Verona
country: Italy
facility: A.O.U.I. Verona
state: Veneto
city: Funabashi
country: Japan
facility: Aiiku Ladies Clinic
state: Chiba
city: Urayasu
country: Japan
facility: Tokyo Bay Urayasu Ichikawa Medical Center
state: Chiba
city: Yotsukaido
country: Japan
facility: Sou Clinic
state: Chiba
city: Sapporo
country: Japan
facility: Teine Keijinkai Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Social Medical Corporation Tokeidai Memorial Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Nishikawa Women's Health Clinic
state: Hokkaido
city: Hitachi
country: Japan
facility: Hitachi General Hospital
state: Ibaraki
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Fujisawa
country: Japan
facility: Fujisawa City Hospital
state: Kanagawa
city: Yokosuka
country: Japan
facility: Yokosuka Kyosai Hospital
state: Kanagawa
city: Kurashiki
country: Japan
facility: Kurashiki Medical Clinic
state: Okayama
city: Suita
country: Japan
facility: Suita Tokushukai Hospital
state: Osaka
city: Kusatsu
country: Japan
facility: Omi Medical Center
state: Shiga
city: Saitama
country: Japan
facility: Kashiwazaki ladies clinic
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Uozu
country: Japan
facility: Toyama Rosai Hospital
state: Toyama
city: Shunan
country: Japan
facility: JCHO Tokuyama Central Hospital
state: Yamaguchi
city: Kumamoto
country: Japan
facility: Japanese Red Cross Kumamoto Hospital
city: Nagasaki
country: Japan
facility: Saiseikai Nagasaki Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Riga
country: Latvia
facility: Latvian Maritime Medicine Center
city: Riga
country: Latvia
facility: Vitols and Vitols Ltd
city: Riga
country: Latvia
facility: I.Vasaraudzes Private Practice
city: Riga
country: Latvia
facility: I.Dinsbergas Physician Practice
city: Vilnius
country: Lithuania
facility: JSC Seimos gydytojas family medical center
city: Vilnius
country: Lithuania
facility: V. Jonaitienes private gynecology clinic
city: Vilnius
country: Lithuania
facility: JSC Gyvenk Silciau Medical Center Maxmeda
city: Fredrikstad
country: Norway
facility: Kirkeparken Spesialistpraksis
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ullevål
city: Tønsberg
country: Norway
facility: Sykehuset i Vestfold HF, Tønsberg
city: Bialystok
country: Poland
facility: Gabinet Ginekologiczny Janusz Tomaszewski
city: Bydgoszcz
country: Poland
facility: MICS Centrum Medyczne Torun
city: Katowice
country: Poland
facility: CLINICAL MEDICAL RESEARCH Sp. z o. o.
city: Katowice
country: Poland
facility: NZOZ MEDEM Wilk Sp. j.
city: Katowice
country: Poland
facility: Vita Longa Sp. z o.o.
city: Lodz
country: Poland
facility: Prywatny Gabinet Lekarski Ginekologia, Poloznictwo i Ultr.
city: Lublin
country: Poland
facility: Specjalistyczny Gabinet Ginekologiczno-Polozniczy
city: Lublin
country: Poland
facility: NZOZ NOVITA, Specjalistyczne Gabinety Lekarskie S.C
city: Szczecin
country: Poland
facility: VitroLive Sp. z o.o.
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp z o.o.
city: Warszawa
country: Poland
facility: Medical Concierge Centrum Medyczne
city: Hlohovec
country: Slovakia
facility: ULMUS, s r.o.
city: Lucenec
country: Slovakia
facility: GA Lucenec s.r.o
city: Velky Krtis
country: Slovakia
facility: Virina sano, s.r.o. Gynekologicko porodnicka ambulancia
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau | Ginecologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
Study officials:
References:
citation: Fletcher MC. Selectivity of the P2X3 receptor antagonist Eliapixant, and its potential use in the treatment of endometriosis. Purinergic Signal. 2022 Mar;18(1):1-3. doi: 10.1007/s11302-021-09831-5. Epub 2022 Jan 3. No abstract available.