26 Week Efficacy and Safety Trial for 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 26 Weeks

Efficacy and Safety Trial of elobixibat in Patients with Chronic Idiopathic Constipation treated for 26 Weeks.

Study Overview

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

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 26-week Treatment Period in patients with chronic idiopathic constipation. Patients were followed-up for 2 weeks after end of the Treatment 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 treatment.

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

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint Luc
  • Ham, Belgium
    • Huisartspraktijk Jaak Mortelmans
  • Leuven, Belgium
    • Universitair Ziekenhuis Leuven
• Brazil
  • São Paulo, Brazil
    • Escola Paulista de Medicina, Universidade Federal de São Paulo
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Hospital de Clínicas de Porto Alegre
  • São Paulo
    • Sant André, São Paulo, Brazil
      • Faculdade de Medicina do ABC
• Canada
  • DrummondvilleQC, Canada
    • Rhodin Recherche Clinique
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • John Buhler Research Center
  • New Brunswick
    • Bathurst, New Brunswick, Canada
      • Maritime Medical Research Center
  • Ontario
    • Toronto, Ontario, Canada
      • Prime Health Clinical Research Organization
  • Quebec
    • Québec, Quebec, Canada
      • Alpha Clinical Research LLC
• Czech Republic
  • Ceské Budejovice, Czech Republic
    • Derma Plus s.r.o.
  • Hradec Králové, Czech Republic
    • Gastroenterologie, s. r. o.
  • Valasske Mezirici, Czech Republic
    • Nemocnice Valasske Mezirici a.s., Gastroenterologicka ambulance
• Germany
  • Berlin, Germany
    • emovis GmbH
  • Berlin, Germany
    • Synexus Clinical Research GmbH
  • Berlin, Germany
    • Universitätsklinik Charité, Campus Mitte
  • Hamburg, Germany
    • Israelitisches Krankenhaus Hamburg
  • Bavaria
    • München, Bavaria, Germany
      • Klinikum der Universität München-Großhadern
  • Hessen
    • Frankfurt am Main, Hessen, Germany
      • Synexus Clinical Research GmbH
  • Niedersachsen
    • Stade, Niedersachsen, Germany
      • Elbe Klinikum Stade - Buxtehude GmbH
  • Nordrhein-westfalen
    • Bochum, Nordrhein-westfalen, Germany
      • Synexus Clinical Research GmbH
  • Sachsen
    • Leipzig, Sachsen, Germany
      • Synexus Clinical Research GmbH
• Israel
  • Beer-Sheva, Israel
    • Soroka University Medical Center
  • Haifa, Israel
    • Bnai Zion Medical Center
  • Jerusalem, Israel
    • Hadassah Medical Organization, Ein Kerem
  • Rehovot, Israel
    • Kaplan Medical Center
  • Tel Hashomer, Israel
    • Sheba Medical Center
  • Zerifin, Israel
    • Assaf Harofeh Medical Centre
• Poland
  • Lodzkie
    • Lódz, Lodzkie, Poland
      • SPZOZ Uniwersytecki Szpital Kliniczny nr 5 im. Gen. Dyw. B. Szareckiego, Uniwersytetu Medycznego
  • Opolskie
    • Opole, Opolskie, Poland
      • Szpital Wojewodzki w Opolu
  • Slaskie
    • Czestochowa, Slaskie, Poland
      • Centrum Medyczne sw. Lukasza Sp. z o.o.
    • Katowice, Slaskie, Poland
      • Neuro-Care NZOZ
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland
      • Pomorski Uniwersytet Medyczny
• South Africa
  • Johannesburg, South Africa
    • The Memory Centre
  • Kraaifontein, South Africa
    • Langeberg Clinical Trials
  • Newtown, South Africa
    • Newtown Clinical Research Centre
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa
      • Global Clinical Trials
  • Free State
    • Bloemfontein, Free State, South Africa
      • Boanerges Clinical Research
  • Gauteng
    • Pretoria, Gauteng, South Africa
      • Synexus Clinical Research SA
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa
      • Parklands Medical Centre
  • Western Cape
    • Worcester, Western Cape, South Africa
      • Boland Ethical Research Group
• United Kingdom
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust
  • England
    • Birmingham, England, United Kingdom
      • Synexus Midlands Clinical Research Centre
    • Durham, England, United Kingdom
      • County Durham and Darlington NHS Foundation Trust
    • Manchester, England, United Kingdom
      • Synexus Manchester Clinical Research Centre
  • Scotland
    • Dundee, Scotland, United Kingdom
      • Tayside University Hospitals NHS Trust, Ninewells Hospital and Medical School
  • Wales
    • Cardiff, Wales, United Kingdom
      • Synexus Wales Clinical Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Alabama Clinical Therapeutics
    • Foley, Alabama, United States
      • G and L Research, LLC
  • Arizona
    • Tucson, Arizona, United States
      • Adobe Gastroenterology Research, LLC
  • California
    • Cerritos, California, United States
      • Skyline Research LLC
    • Chula Vista, California, United States
      • GW Research, Inc.
    • Garden Grove, California, United States
      • Paradigm Clinical, Inc.
    • North Hollywood, California, United States
      • Providence Clinical Research
  • Connecticut
    • Stamford, Connecticut, United States
      • Stamford Therapeutics Consortium
  • Florida
    • Brandon, Florida, United States
      • Pulmonary Associates of Brandon
    • Hialeah, Florida, United States
      • In Vivo Clinical Research, Inc.
    • Hialeah, Florida, United States
      • Medsearch Professional Group, Inc.
    • Hialeah, Florida, United States
      • The Community Research of South Florida
    • Hollywood, Florida, United States
      • Center for Gastrointestinal Disorders
    • Inverness, Florida, United States
      • Nature Coast Clinical Research, LLC
    • Jacksonville, Florida, United States
      • Gastroenterology and Hepatology Associates
    • Jupiter, Florida, United States
      • Jupiter Research Inc.
    • Maitland, Florida, United States
      • Center For Advanced Gastroenterology
    • Miami, Florida, United States
      • Advanced Pharma CR, LLC
    • Miami, Florida, United States
      • Research Institute of South Florida
    • Naples, Florida, United States
      • Gastroenterology Group Of Naples
    • West Palm Beach, Florida, United States
      • Palm Beach Research Center
  • Georgia
    • Snellville, Georgia, United States
      • Georgia Clinical Research
  • Idaho
    • Blackfoot, Idaho, United States
      • Elite Clinical Trials, Inc.
  • Indiana
    • Evansville, Indiana, United States
      • Medisphere Medical Research Center, Llc
  • Maryland
    • Hollywood, Maryland, United States
      • MidAtlantic Medical Research Centers, Philip J. Bean Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston Clinical Trials
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan Health System
  • Missouri
    • Lee's Summit, Missouri, United States
      • Midwest Gastroenterology Partners
  • Nevada
    • Las Vegas, Nevada, United States
      • Advanced Biomedical Research of America
  • New Hampshire
    • Newington, New Hampshire, United States
      • ActivMed Practices and Research, Inc.
  • New York
    • Brooklyn, New York, United States
      • HOSC, Inc.
    • Valley Stream, New York, United States
      • North American Partners in Pain Management
  • North Carolina
    • Davidson, North Carolina, United States
      • Carolina Digestive Health Associates, PA
    • Fayetteville, North Carolina, United States
      • Cumberland Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States
      • Gastroenterology Research Consultants of Greater Cincinnati
    • Groveport, Ohio, United States
      • Hometown Urgent Care and Occupational Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Oklahoma Foundation for Digestive Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Clinical Trials Research Services, LLC
    • Souderton, Pennsylvania, United States
      • Mainline Gastroenterology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States
      • ClinSearch
    • Germantown, Tennessee, United States
      • Memphis Gastroenterology Group, PC
  • Texas
    • Dallas, Texas, United States
      • KRK Medical Research
    • Dallas, Texas, United States
      • Research Across America
    • Houston, Texas, United States
      • Pioneer Research Solutions, Inc.
    • Sugar Land, Texas, United States
      • Pioneer Research Solutions, Inc.
  • Washington
    • Bellevue, Washington, United States
      • Northwest Gastroenterology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 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 GI tract or a disease or condition that can affect Gastrointestinal (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 manoeuvres (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 Assignment
• 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; Elobixibat 10 mg/day; Other Names: A3309
Experimental: EBX 5; Elobixibat 5 mg/day	Drug: Elobixibat 5 mg; 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
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 the first 24 hours of treatment initiation
Change From Baseline in Weekly Frequency of Spontaneous Bowel Movements (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
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
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 of 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 12 weeks
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 Bloating Score	The abdominal bloating 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
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

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): May 1, 2014

Study Registration Dates

• First Submitted: April 5, 2013
• First Submitted That Met QC Criteria: April 5, 2013
• First Posted (Estimate): April 9, 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: 000079; 2012-005587-94 (EudraCT Number)