Clinical trial NCT01833065: Efficacy and Safety Trial of Elobixibat in Patients With Chronic Idiopathic Constipation
Official title: A Double-blind, Randomised, Placebo-controlled, Phase 3 Trial in Patients With Chronic Idiopathic Constipation to Demonstrate the Efficacy and Safety of Elobixibat 5 mg and 10 mg for 12 Weeks Followed by a 4-week Withdrawal Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Idiopathic Constipation
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-04-16
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 12 Week Efficacy and Safety Trial Followed by a 4 Week Withdrawal Period for Patients with Chronic Idiopathic Constipation.

Detailed description: The present trial was designed to determine the efficacy and safety of elobixibat treatment (at both doses of 5 mg and 10 mg/day) compared to placebo treatment for 12-week Treatment Period followed by a 4-week Withdrawal Period in patients with chronic idiopathic constipation. During Withdrawal Period a sub-group of patients in elobixibat 5 mg and 10 mg treatment arms respectively received placebo treatment, while rest of the patients continued with 5 mg and 10 mg treatment in respective groups. In placebo groups, patients received elobixibat 10 mg treatment during Withdrawal Period. Patients were followed-up for 2 weeks after end of the Withdrawal Period.

The assessment of primary and key secondary end points was done for patients who completed the first 12 weeks of treatment period. Incidence of Adverse Events (AEs) were reported till 2 weeks after end of the Withdrawal Period.

The trial was early terminated due to a distribution issue with the trial medication.

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) ≥18.5 but \<35.0 kg/m\^2
* Male or female ≥18 years of age
* Reports \<3 spontaneous Bowel Movements (BM) per week and reports one or more of the following symptoms for the last 3 months with symptom onset at least 6 months before the Screening Visit or before starting chronic therapy with any laxative:

  1. Straining during at least 25% of defecations
  2. Lumpy or hard stools during at least 25% of defecations
  3. Sensation of incomplete evacuation during at least 25% of defecations
* Is ambulatory and community dwelling
* An initial colonoscopy is required if recommended by national guidelines

Exclusion Criteria:

* Reports loose (mushy) or watery stools in the absence of any laxative intake in the form of a tablet, a suppository or an enema, or prohibited medicine for \>25% of BMs
* The patient reports a BSFS of 6 or 7 during the Pretreatment Period
* Has irritable bowel syndrome (IBS) with pain/discomfort as predominant symptoms
* Has a structural abnormality of the Gastrointestinal (GI) tract or a disease or condition that can affect GI motility
* Has a history of diverticulitis, chronic pancreatitis, active peptic ulcer disease (PUD) not adequately treated, ischaemic colitis, inflammatory bowel disease, laxative abuse, faecal impaction that required hospitalization or emergency treatment, pseudo-obstruction, megacolon, megarectum, bowel obstruction, descending perineum syndrome, ovarian cysts, endometriosis, solitary rectal ulcer syndrome, systemic sclerosis, pre-malignant colonic disease (e.g., familial adenomatous polyposis or hereditary non-polyposis colorectal cancer) or other forms of familial colorectal cancer
* Has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or heme-positive stool in the absence of known internal or external haemorrhoids, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis
* Has a potential central nervous system (CNS) cause of constipation (e.g., Parkinson's disease, spinal cord injury, multiple sclerosis)
* Has intestinal/rectal prolapse or other known pelvic floor dysfunction
* Commonly uses digital maneuvers (perianal pressure or digital disimpaction) or vaginal splinting to facilitate the passage of a bowel movement
* Has a history of diabetic neuropathy
* Has a history of bariatric surgery for treatment of obesity; surgery to remove a segment of the GI tract; or surgery of the abdomen, pelvic or retroperitoneal area during the 6 months prior to Screening; or appendectomy or cholecystectomy 3 months prior to screening; or other major surgery 1 month prior to Screening
* Has a history of cancer with last date of proven disease activity/presence of malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the cervix
* Known human immunodeficiency virus (HIV) or Hepatitis B/C (HBV/HCV) infection
* Has a history of hospitalization for any psychiatric disorder, or any suicide attempt in the 2 years prior to Screening
* Is actively abusing alcohol or drugs or has a history of alcohol or drug abuse during the 6 months prior to Screening
* Is being treated for hypothyroidism, but the dose of medication has not been stable for at least 3 months at the time of Screening
* Is a pregnant, breast-feeding, or lactating woman

Primary outcomes:
measure: Overall Complete Spontaneous Bowel Movement (CSBM) Response
timeFrame: During the first 12 weeks
Secondary outcomes:
measure: Occurrence of CSBM Response
timeFrame: Within first 24 hours of treatment initiation
measure: Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs)
timeFrame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
measure: Change From Baseline in Weekly Stool Consistency of SBMs
timeFrame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
measure: Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder
timeFrame: At Week 12
measure: Change From Baseline in Weekly Degree of Straining of SBMs
timeFrame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
measure: Change From Baseline in Weekly Abdominal Bloating Score
timeFrame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
measure: Change From Baseline in Weekly Abdominal Discomfort Score
timeFrame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Associates, PC
state: Alabama
city: Tucson
country: United States
facility: Genova Clinical Research, Inc.
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: West Gastroenterology Associates
state: California
city: Sacramento
country: United States
facility: Sacramento Research Medical Group
state: California
city: San Diego
country: United States
facility: Precision Research Institute, LLC
state: California
city: Bridgeport
country: United States
facility: Gastroenterology Associates of Fairfield County
state: Connecticut
city: Boynton Beach
country: United States
facility: Zasa Clinical Research
state: Florida
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Coral Gables
country: United States
facility: Sanitas Research
state: Florida
city: Eustis
country: United States
facility: Lake Internal Medicine Associates
state: Florida
city: Hialeah
country: United States
facility: Health Care Family Rehab Corp.
state: Florida
city: Jacksonville
country: United States
facility: Southeast Clinical Research, LLC
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Atlanta
country: United States
facility: Mount Vernon Clinical Research
state: Georgia
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Evanston
country: United States
facility: Premier Healthcare Research, LLC
state: Illinois
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates, Ltd.
state: Illinois
city: Augusta
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Witchita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group
state: New York
city: Charlotte
country: United States
facility: Carolina Digestive Health Associates, PA
state: North Carolina
city: Concord
country: United States
facility: Carolina Digestive Health Associates, PA
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest, LLC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Columbus
country: United States
facility: Hometown Urgent Care and Occupational Health
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Occupational Health
state: Ohio
city: Wadsworth
country: United States
facility: Family Practice Center of Wadsworth
state: Ohio
city: Oklahoma City
country: United States
facility: Clinical Research Associates, LLC
state: Oklahoma
city: Medford
country: United States
facility: Sunstone Medical Research, LLC
state: Oregon
city: Levittown
country: United States
facility: Family Medical Associates
state: Pennsylvania
city: Anderson
country: United States
facility: Anderson Gastroenterology Associates
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Hermitage
country: United States
facility: Associates in Gastroenterology, LLC
state: Tennessee
city: Jackson
country: United States
facility: HCCA Clinical Research Solutions
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research and Development, LLC
state: Tennessee
city: Katy
country: United States
facility: Research Across America
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Juiz de Fora
country: Brazil
facility: Fundacao IMEPEM - Universidade Federal de Juiz de Fora
state: Minas Gerais
city: Rio de Janeiro
country: Brazil
facility: Gastrocentro Carioca Centro Gast e Endosc Dig, Ltda
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Penticton
country: Canada
facility: Medical Arts Health Research Group
state: British Columbia
city: Sarnia
country: Canada
facility: London Road Diagnostic Clinic and Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Dr Anil K Gupta Medicine Professional Corp.
state: Ontario
city: Toronto
country: Canada
facility: Toronto Digestive Diseases Associates, Inc.
state: Ontario
city: Saint Romuald
country: Canada
facility: Pro-Recherche Polyclinique des Ponts
state: Quebec
city: Ostrava
country: Czech Republic
facility: Fakultní Nemocnice Ostrava
state: Severomoravsky Kraj
city: Ceské Budejovice
country: Czech Republic
facility: Gastroenterologicka a interni ambulance
city: Magdeburg
country: Germany
facility: Synexus Clinical Research GmbH
state: Sachsen-anhalt
city: Dresden
country: Germany
facility: Synexus Clinical Research GmbH
state: Sachsen
city: Görlitz
country: Germany
facility: Synexus Clinical Research GmbH
state: Sachsen
city: Gyula
country: Hungary
facility: Pándy Kálmán Megyei Kórház
state: Bekes
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-Pesti Kórház és Rendelointézet
city: Budapest
country: Hungary
facility: Pannónia Magánorvosi Centrum Kft.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft
city: Miskolc
country: Hungary
facility: Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
city: Miskolc
country: Hungary
facility: Miskolci Semmelweis Kórház és Egyetemi Oktatókórház
city: Szekszárd
country: Hungary
facility: Clinfan Szolgáltató Kft
city: Szikszó
country: Hungary
facility: CRU Hungary Kft.
city: Vác
country: Hungary
facility: Jávorszky Ödön Kórház
city: Guadalajara
country: Mexico
facility: Centro de Investigación Médico Biológica y Terapia Avanzada SC
state: Jalisco
city: Monterrey
country: Mexico
facility: Accelerium Clinical Research
state: Nuevo Leon
city: Mérida
country: Mexico
facility: Medical Care and Research
state: Yucatan
city: Chihuahua
country: Mexico
facility: Hospital Centro Internacional de Medicina Chihuahua
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Adam Kopon
state: Kujawsko-pomorskie
city: Lódz
country: Poland
facility: SPZOZ Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
state: Lodzkie
city: Kraków
country: Poland
facility: Krakowskie Centrum Medyczne Sp. z o.o.
state: Malopolskie
city: Warszawa
country: Poland
facility: Medica Pro Familia Sp. z o.o. S.K.A.
state: Mazowieckie
city: Warszawa
country: Poland
facility: Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ
state: Mazowieckie
city: Rzeszów
country: Poland
facility: Medicor Centrum Medyczne Tadeusz Mazurek
state: Podkarpackie
city: Bratislava
country: Slovakia
facility: Lama Medical Care s.r.o., Gastroentero-hepatologicke centrum Thalion
city: Martin
country: Slovakia
facility: PIGEAS s.r.o.
city: Nitra
country: Slovakia
facility: KM Management sro
city: Prešov
country: Slovakia
facility: Gastro I.s.r.o.
city: Trnava
country: Slovakia
facility: GEA s.r.o Gastroenterologicka ambulancia
city: Bloemfontein
country: South Africa
facility: JOSHA Research
state: Free State
city: Pretoria
country: South Africa
facility: Synexus Clinical Research SA
state: Gauteng
city: Durban
country: South Africa
facility: Dr. Zubar Fazel Vawda
state: KwaZulu-Natal
city: Middelburg
country: South Africa
facility: Mzansi Ethical Research Centre
state: Mpumalanga
city: Bellville
country: South Africa
facility: Louis Leipoldt Medi-Clinic Medical Centre
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre
state: Western Cape
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Sjukhus
city: Chorley
country: United Kingdom
facility: Synexus Lancashire Clinical Research Centre
state: England
city: Liverpool
country: United Kingdom
facility: Synexus Merseyside Clinical Research Centre
state: England
city: Reading
country: United Kingdom
facility: Synexus Thames Valley Clinical Research Centre
state: England
city: Glasgow
country: United Kingdom
facility: Synexus Scotland Clinical Research Centre
state: Scotland
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References: