Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation

A Multicenter, Open-label, Safety and Tolerability Extension Trial of 5 mg and 10 mg Elobixibat Daily in the Treatment of Chronic Idiopathic Constipation

Safety and Tolerability Extension Trial for Patients with Chronic Idiopathic Constipation (CIC)

Study Overview

• Status: Completed
• Conditions: Chronic Idiopathic Constipation
• Intervention / Treatment: Drug: Elobixibat 10 mg

Detailed Description

This was a Phase 3 multicenter, open-label, safety and tolerability extension trial of 10 mg elobixibat daily, with possibility for dose adjustment to 5 mg daily, for 52-week Treatment Period in patients with CIC. A dose adjustment to 5 mg/day was allowed for the remainder of the trial if a patient reported unacceptable treatment-related diarrhoea that occurred within the first four weeks of treatment.

The trial enrolled patients from two lead-in, double-blind efficacy trials (trial codes NCT01827592 and NCT01833065).

• Study Type: Interventional
• Enrollment (Actual): 411
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint Luc (there may be other sites in this country)
• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Prime Health Clinical Research Organization (there may be other sites in this country)
• Czech Republic
  • Hradec Králové, Czech Republic
    • Gastroenterologie, s. r. o. (there may be other sites in this country)
• Hungary
  • Budapest, Hungary
    • Pannónia Magánorvosi Centrum Kft. (there may be other sites in this country)
• Poland
  • Lodzkie
    • Lódz, Lodzkie, Poland
      • SPZOZ Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi (there may be other sites in this country)
• Slovakia
  • Nitra, Slovakia
    • KM Management sro (there may be other sites in this country)
• South Africa
  • Western Cape
    • Bellville, Western Cape, South Africa
      • Louise Lelpoldt Medical Centre (there may be other sites in this country)
• Sweden
  • Uppsala, Sweden
    • Uppsala Akademiska Sjukhus (there may be other sites in this country)
• United Kingdom
  • England
    • Liverpool, England, United Kingdom
      • Synexus Merseyside Clinical Research Centre (there may be other sites in this country)
• United States
  • 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
    • Cerritos, California, United States
      • Skyline Research, LLC
    • Los Angeles, California, United States
      • West Gastroenterology Associates
    • Sacramento, California, United States
      • Sacramento Research Medical Group
  • Connecticut
    • Stamford, Connecticut, United States
      • Stamford Therapeutics Consortium
  • Florida
    • Boynton Beach, Florida, United States
      • Zasa Clinical Research
    • Bradenton, Florida, United States
      • Meridien Research
    • Brandon, Florida, United States
      • Pulmonary Associates of Brandon
    • Hialeah, Florida, United States
      • Medsearch Professional Group, Inc.
    • Hialeah, Florida, United States
      • The Community Research of South Florida
    • Hialeah, Florida, United States
      • Health Care Family Rehab Corp.
    • Hollywood, Florida, United States
      • Center for Gastrointestinal Disorders
    • Inverness, Florida, United States
      • Nature Coast Clinical Research, LLC
    • Jupiter, Florida, United States
      • Jupiter Research Inc.
    • Jupiter, Florida, United States
      • Health Awareness, Inc.
    • Miami, Florida, United States
      • Advanced Pharma CR, LLC
    • Miami, Florida, United States
      • Research Institute of South Florida
    • West Palm Beach, Florida, United States
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States
      • Mount Vernon Clinical Research
    • Snellville, Georgia, United States
      • Georgia Clinical Research
  • Illinois
    • Evanston, Illinois, United States
      • Evanston Hospital
    • Rockford, Illinois, United States
      • Rockford Gastroenterology Associates, Ltd.
  • Indiana
    • Evansville, Indiana, United States
      • MediSphere Medical Research Center, LLC
  • Kansas
    • Augusta, Kansas, United States
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States
      • Heartland Research Associates, LLC
  • Louisiana
    • Shreveport, Louisiana, United States
      • Louisiana Research Center, LLC
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston Clinical Trials
    • Brockton, Massachusetts, United States
      • Beacon Clinical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States
      • Quality Clinical Research, Inc.
  • 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
    • Great Neck, New York, United States
      • Long Island Gastrointestinal Research Group
  • North Carolina
    • Concord, North Carolina, United States
      • Carolina Digestive Health Associates, PA
    • Fayetteville, North Carolina, United States
      • Cumberland Research Associates, LLC
    • Greensboro, North Carolina, United States
      • PharmQuest, LLC
    • High Point, North Carolina, United States
      • Peters Medical Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States
      • TriHealth, Inc.
  • 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
    • Pittsburg, Pennsylvania, United States
      • Clinical Trials Research Services, LLC
  • South Carolina
    • Anderson, South Carolina, United States
      • Anderson Gastroenterology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States
      • ClinSearch
    • Germantown, Tennessee, United States
      • Memphis Gastroenterology Group, PC
    • Hermitage, Tennessee, United States
      • Associates in Gastroenterology, LLC
    • Jackson, Tennessee, United States
      • HCCA Clinical Research Solutions
  • Texas
    • Dallas, Texas, United States
      • KRK Medical Research
    • Houston, Texas, United States
      • Pioneer Research Solutions, Inc.
    • Sugar Land, Texas, United States
      • Pioneer Research Solutions, Inc.
  • Virginia
    • Chesapeake, Virginia, United States
      • Gastroenterology Associates of Tidewater
  • Washington
    • Bellevue, Washington, United States
      • Northwest Gastroenterology Associates

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:

• Has completed double-blind treatment in either of the lead-in efficacy trials, 000079 or 000080.
• The patient reports having understood and has signed the Informed Consent Form (ICF) and is willing to comply with all trial visits and assessments.
• The patient agrees to refrain from making any new, major lifestyle changes that may affect CIC symptoms (i.e., starting a new diet, changing an exercise plan) from the time of signing the ICF through to the last trial visit.

Exclusion Criteria:

• The patient has been withdrawn/discontinued from the 000079 or 000080 trials.
• The patient is not willing to abide by the restrictions for intake of prohibited medication.

• Women of childbearing potential (defined, for the purpose of this trial, as all females post-puberty, not postmenopausal ≥2 years, or not surgically sterile) who have a positive urine pregnancy test at Visit 1, or who do not agree to use one of the following methods of birth control from the day of signing the ICF until 30 days after the final dose of trial drug are excluded:

  1. Transdermal patch
  2. Established use of oral, injected or implanted hormonal methods of contraception
  3. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  4. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  5. Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
  6. True sexual abstinence: when this is in line with the preferred and usual lifestyle of the patient.
• The patients is considered by the Investigator to be unsuitable to participate in the trial for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EBX10; Elobixibat 10 mg	Drug: Elobixibat 10 mg; 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)	The Investigator recorded all AEs throughout the trial from the time of obtaining informed consent till the last visit (i.e., Visit 6). Information on AE was collected at each visit. All AEs were recorded in AE log for each patient.	For the overall 52-week Treatment Period
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables	Outcome measure include laboratory parameters from haematology, coagulation and clinical chemistry	For the overall 52-week Treatment Period
Incidence of Markedly Abnormal Changes in Electrocardiograms (ECGs)	A routine 12-lead ECG was performed at all visits. The ECG included heart rate, PR, QRS, and QT intervals assessment.	For the overall 52-week Treatment Period
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs	Vital signs were measured at all visits and included blood pressure (BP: measured after the patient had been in a seated position for ≥3 minutes of rest), pulse, respiration rate, body temperature, and body weight.	For the overall 52-week Treatment Period
Number of Patients Using Concomitant Medications	The concomitant medications details were collected throughout the trial at all visits. Data were obtained at scheduled or unscheduled trial visits based on information provided spontaneously by the patient or as a result of questioning the patient.	For the overall 52-week Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of Concomitant Over-the-counter (OTC) Laxatives	The use of OTC laxatives during the trial was assessed based upon the concomitant medication module of the electronic Case Report Form (eCRF).	For the overall 52-week Treatment Period
Change From Baseline in Global Evaluation of Constipation Severity	The constipation severity score was measured on a 5-point scale (1: none to 5: very severe).	At Week 12, 24, 36, and 52
Change From Baseline in Global Evaluation of Treatment Effectiveness	The treatment effectiveness score was measured on a 5-point scale (1: extremely effective, 2: quite a bit effective, 3: moderately effective, 4: little bit effective, 5: not at all effective).	At Week 12, 24, 36, and 52
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score	PAC-QOL is a 28-item questionnaire for psychometric assessment of disease-specific QOL. The questionnaire is based on a 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 QOL. The PAC-QOL questionnaire is developed specifically for patients with constipation. PAC-QOL has four sub-scales: 'Worries and Concerns', 'Physical Discomfort', 'Psychosocial Discomfort', and 'Dissatisfaction'.	At Week 12, 24, 36 and 52
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores	EQ-5D-5L is a standardised measure of health status developed to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L descriptive system comprises the following five dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels (1-5 denotes): no problems, slight problems, moderate problems, severe problems, and extreme problems, respectively. A unique health state was defined by combining 1 level from each of the 5 dimensions. Each health state was converted into a single EQ-5D-5L index value. The index values are country specific and values specified for United Kingdom (UK) were used for this study. The index value range for UK lies between -0.594 - 1.000. A positive index value represents better health status while the negative value represents poor health status.	At Week 12, 24, 36 and 52
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score	The EQ VAS presents the participant's self-evaluated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100, where '100' means best health you can imagine and '0' means worst health you can imagine. The participant simply mark an 'X' on the scale to indicate "how his/her health is TODAY" and mention the same number in a box provided.	At Week 12, 24, 36 and 52

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): May 9, 2016
• Last Update Submitted That Met QC Criteria: April 29, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: 000081; 2012-005601-46 (EUDRACT_NUMBER)