Efficacy and Safety Trial of Elobixibat in Patients With Chronic Idiopathic Constipation

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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Idiopathic Constipation
• Intervention / Treatment: Drug: Placebo; Drug: Elobixibat 10 mg/day; Drug: Elobixibat 5 mg/day

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.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Gastrocentro Carioca Centro Gast e Endosc Dig, Ltda
  • São Paulo, Brazil
    • Hospital Israelita Albert Einstein
  • Minas Gerais
    • Juiz de Fora, Minas Gerais, Brazil
      • Fundacao IMEPEM - Universidade Federal de Juiz de Fora
• Canada
  • British Columbia
    • Penticton, British Columbia, Canada
      • Medical Arts Health Research Group
  • Ontario
    • Sarnia, Ontario, Canada
      • London Road Diagnostic Clinic and Medical Centre
    • Toronto, Ontario, Canada
      • Dr Anil K Gupta Medicine Professional Corp.
    • Toronto, Ontario, Canada
      • Toronto Digestive Diseases Associates, Inc.
  • Quebec
    • Saint Romuald, Quebec, Canada
      • Pro-Recherche Polyclinique des Ponts
• Czech Republic
  • Ceské Budejovice, Czech Republic
    • Gastroenterologicka a interni ambulance
  • Severomoravsky Kraj
    • Ostrava, Severomoravsky Kraj, Czech Republic
      • Fakultni nemocnice Ostrava
• Germany
  • Sachsen
    • Dresden, Sachsen, Germany
      • Synexus Clinical Research GmbH
    • Görlitz, Sachsen, Germany
      • Synexus Clinical Research GmbH
  • Sachsen-anhalt
    • Magdeburg, Sachsen-anhalt, Germany
      • Synexus Clinical Research GmbH
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem
  • Budapest, Hungary
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Budapest, Hungary
    • Pannonia Maganorvosi Centrum Kft.
  • Debrecen, Hungary
    • Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft
  • Miskolc, Hungary
    • Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
  • Miskolc, Hungary
    • Miskolci Semmelweis Kórház és Egyetemi Oktatókórház
  • Szekszárd, Hungary
    • CLINFAN Szolgáltató Kft
  • Szikszó, Hungary
    • CRU Hungary Kft.
  • Vác, Hungary
    • Javorszky Odon Korhaz
  • Bekes
    • Gyula, Bekes, Hungary
      • Pándy Kálmán Megyei Kórház
• Mexico
  • Chihuahua, Mexico
    • Hospital Centro Internacional de Medicina Chihuahua
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • Centro de Investigacion Medico Biologica y Terapia Avanzada SC
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
      • Accelerium Clinical Research
  • Yucatan
    • Mérida, Yucatan, Mexico
      • Medical Care and Research
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland
      • Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
    • Torun, Kujawsko-pomorskie, Poland
      • Indywidualna Specjalistyczna Praktyka Lekarska Adam Kopon
  • Lodzkie
    • Lódz, Lodzkie, Poland
      • SPZOZ Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Malopolskie
    • Kraków, Malopolskie, Poland
      • Krakowskie Centrum Medyczne Sp. z o.o.
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland
      • Medica Pro Familia sp. z o.o. S.K.A.
    • Warszawa, Mazowieckie, Poland
      • Przychodnia Polskiej Fundacji Gastroenterologii Filia Nr 1 NZOZ
  • Podkarpackie
    • Rzeszów, Podkarpackie, Poland
      • Medicor Centrum Medyczne Tadeusz Mazurek
• Slovakia
  • Bratislava, Slovakia
    • Lama Medical Care s.r.o., Gastroentero-hepatologicke centrum Thalion
  • Martin, Slovakia
    • Pigeas s.r.o.
  • Nitra, Slovakia
    • KM Management sro
  • Prešov, Slovakia
    • Gastro I.s.r.o.
  • Trnava, Slovakia
    • GEA s.r.o Gastroenterologicka ambulancia
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa
      • Josha Research
  • Gauteng
    • Pretoria, Gauteng, South Africa
      • Synexus Clinical Research SA
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa
      • Dr. Zubar Fazel Vawda
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa
      • Mzansi Ethical Research Centre
  • Western Cape
    • Bellville, Western Cape, South Africa
      • Louis Leipoldt Medi-Clinic Medical Centre
    • Paarl, Western Cape, South Africa
      • Be Part Yoluntu Centre
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
  • Stockholm, Sweden
    • Karolinska University Hospital Huddinge
  • Uppsala, Sweden
    • Uppsala Akademiska Sjukhus
• United Kingdom
  • England
    • Chorley, England, United Kingdom
      • Synexus Lancashire Clinical Research Centre
    • Liverpool, England, United Kingdom
      • Synexus Merseyside Clinical Research Centre
    • Reading, England, United Kingdom
      • Synexus Thames Valley Clinical Research Centre
  • Scotland
    • Glasgow, Scotland, United Kingdom
      • Synexus Scotland Clinical Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Birmingham Gastroenterology Associates, PC
  • Arizona
    • Tucson, Arizona, United States
      • Genova Clinical Research, Inc.
  • Arkansas
    • Little Rock, Arkansas, United States
      • Preferred Research Partners
    • North Little Rock, Arkansas, United States
      • Arkansas Gastroenterology
  • California
    • Los Angeles, California, United States
      • David Geffen School of Medicine at University of California, Los Angeles
    • Los Angeles, California, United States
      • West Gastroenterology Associates
    • Sacramento, California, United States
      • Sacramento Research Medical Group
    • San Diego, California, United States
      • Precision Research Institute, LLC
  • Connecticut
    • Bridgeport, Connecticut, United States
      • Gastroenterology Associates of Fairfield County
  • Florida
    • Boynton Beach, Florida, United States
      • Zasa Clinical Research
    • Bradenton, Florida, United States
      • Meridien Research
    • Coral Gables, Florida, United States
      • Sanitas Research
    • Eustis, Florida, United States
      • Lake Internal Medicine Associates
    • Hialeah, Florida, United States
      • Health Care Family Rehab Corp.
    • Jacksonville, Florida, United States
      • Southeast Clinical Research, LLC
    • Jupiter, Florida, United States
      • Health Awareness, Inc.
  • Georgia
    • Atlanta, Georgia, United States
      • Mount Vernon Clinical Research
    • Columbus, Georgia, United States
      • Southeast Regional Research Group
  • Illinois
    • Evanston, Illinois, United States
      • Premier Healthcare Research, LLC
    • Rockford, Illinois, United States
      • Rockford Gastroenterology Associates, Ltd.
  • Kansas
    • Augusta, Kansas, United States
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States
      • Heartland Research Associates, LLC
    • Witchita, Kansas, United States
      • Professional Research Network of Kansas, LLC
  • Louisiana
    • Shreveport, Louisiana, United States
      • Louisiana Research Center, LLC
  • Massachusetts
    • Brockton, Massachusetts, United States
      • Beacon Clinical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States
      • Quality Clinical Research, Inc.
  • New York
    • Great Neck, New York, United States
      • Long Island Gastrointestinal Research Group
  • North Carolina
    • Charlotte, North Carolina, United States
      • Carolina Digestive Health Associates, PA
    • Concord, North Carolina, United States
      • Carolina Digestive Health Associates, PA
    • Greensboro, North Carolina, United States
      • Pharmquest, LLC
    • High Point, North Carolina, United States
      • Peters Medical Research, LLC
    • Raleigh, North Carolina, United States
      • Wake Research Associates, LLC
  • Ohio
    • Columbus, Ohio, United States
      • Hometown Urgent Care and Occupational Health
    • Dayton, Ohio, United States
      • Hometown Urgent Care and Occupational Health
    • Wadsworth, Ohio, United States
      • Family Practice Center of Wadsworth
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Clinical Research Associates, LLC
  • Oregon
    • Medford, Oregon, United States
      • Sunstone Medical Research, LLC
  • Pennsylvania
    • Levittown, Pennsylvania, United States
      • Family Medical Associates
  • South Carolina
    • Anderson, South Carolina, United States
      • Anderson Gastroenterology Associates
    • Summerville, South Carolina, United States
      • Palmetto Clinical Research
  • Tennessee
    • Hermitage, Tennessee, United States
      • Associates in Gastroenterology, LLC
    • Jackson, Tennessee, United States
      • HCCA Clinical Research Solutions
    • Knoxville, Tennessee, United States
      • New Phase Research and Development, LLC
  • Texas
    • Katy, Texas, United States
      • Research Across America
  • Virginia
    • Chesapeake, Virginia, United States
      • Gastroenterology Associates of Tidewater

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EBX 10; Elobixibat 10 mg/day	Drug: Elobixibat 10 mg/day; Elobixibat 10 mg/day; Other Names: A3309
EXPERIMENTAL: EBX 5; Elobixibat 5 mg/day	Drug: Elobixibat 5 mg/day; Elobixibat 5 mg/day; Other Names: A3309
PLACEBO_COMPARATOR: PLCBO; Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Complete Spontaneous Bowel Movement (CSBM) Response	This outcome measured the percentage of patients who were CSBM responders. A CSBM responder was defined as a patient with ≥3 CSBMs per week and an increase of ≥1 CSBM per week from Baseline, for at least 9 of the 12 weeks in the 12-week Treatment Period, including at least 3 weeks during Weeks 9-12.	During the first 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Stool Consistency of SBMs	The stool consistency is measured using the seven-point ordinal Bristol Stool Form Scale (BSFS) score. The BSFS classifies human stool into seven types and points them accordingly. Type 1: Separate hard lumps, like nuts (hard to pass) Type 2: Sausage-shaped, but lumpy Type 3: Like a sausage but with cracks on its surface Type 4: Like a sausage or snake, smooth and soft Type 5: Soft blobs with clear cut edges (passed easily) Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces, entirely liquid Types 1 and 2 indicate constipation, with 3 and 4 represents the ideal stool form (especially the latter), and 5, 6 and 7 tends towards diarrhoea . For a given assessment week, the weekly stool consistency was defined as the sum of non-missing stool consistency score for SBMs during that week divided by the number of non-missing stool consistency score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.	From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Change From Baseline in Weekly Degree of Straining of SBMs	The degree of straining was measured using the five-point ordinal scale (1=Not at all, 2=A little bit, 3=A moderate amount, 4=A great deal, and 5=An extreme amount). For a given assessment week, the weekly degree of straining was defined as the sum of non-missing straining score for SBMs during that week divided by the number of non-missing straining score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.	From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Change From Baseline in Weekly Abdominal Discomfort Score	The abdominal discomfort score was measured using the five-point ordinal scale (1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very severe). For a given assessment week, the weekly abdominal discomfort score was defined as the sum of non-missing abdominal discomfort score for SBMs during that week divided by the number of non-missing abdominal discomfort score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.	From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Occurrence of CSBM Response	This outcome measured the percentage of patients who had a CSBM within 24 hours after the first dose of treatment. A CSBM was defined as a spontaneous (occurring without laxative within the preceding 24 hours, including no rescue medication within the preceding 24 hours) bowel movement (as interpreted by the patient, with a beginning and an end, including single or multiple stools), accompanied by a patient reported sense of complete evacuation ('complete').	Within first 24 hours of treatment initiation
Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs)	The change from Baseline for the continuous variable was estimated using a repeated measures analysis of covariance (ANCOVA) model.	From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder	This outcome measured the percentage of patients who were PAC-QOL score responder at 12-week Treatment Period. A PAC-QOL score responder was defined as a patient with ≥50% reduction in total PAC-QOL score from Baseline at Week 12. PAC-QOL is a 28-item questionnaire for psychometric assessment of disease-specific quality of life. The questionnaire is based on 5-point Likert scale; ranging from 0 [none of the time or not at all] to 4 [all of the time or extremely]). A lower score indicates a better Quality of Life. The PAC-QOL questionnaire is developed specifically for patients with constipation. Total PAC-QOL score was averaged from the individual item score.	At Week 12
Change From Baseline in Weekly Abdominal Bloating Score	The abdominal pain score was measured using the five-point ordinal scale (1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very severe). For a given assessment week, the weekly abdominal bloating score was defined as the sum of non-missing abdominal bloating score for SBMs during that week divided by the number of non-missing abdominal bloating score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.	From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: April 12, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (ESTIMATE): April 16, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 20, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: 000080 (OTHER: Clinical Center, NIH); 2012-005588-28 (EUDRACT_NUMBER)