26 Week Efficacy and Safety Trial for Patients With Chronic Idiopathic Constipation

Chronic Idiopathic Constipation Clinical Trial

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 26 Weeks

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01827592
• Other study ID #: 000079
• Secondary ID: 2012-005587-94
• Status: Terminated
• Phase: Phase 3
• First received: April 5, 2013
• Last updated: September 22, 2015
• Start date: April 2013
• Est. completion date: May 2014

Study information

• Verified date: September 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesIsrael: Israeli Health Ministry Pharmaceutical AdministrationPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSouth Africa: Medicines Control CouncilUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 376
• Est. completion date: May 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Idiopathic Constipation
• Constipation

Intervention

Drug:
• Elobixibat 10 mg
Elobixibat 10 mg/day
• Elobixibat 5 mg
Elobixibat 5 mg/day
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Czech Republic,  Germany,  Israel,  Poland,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No