Efficacy and Safety Trial of Elobixibat in 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 12 Weeks Followed by a 4-week Withdrawal Period

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01833065
• Other study ID #: 000080
• Secondary ID: 2012-005588-28
• Status: Terminated
• Phase: Phase 3
• First received: April 12, 2013
• Last updated: September 22, 2015
• Start date: April 2013
• Est. completion date: April 2014

Study information

• Verified date: September 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyMexico: Federal Commission for Sanitary Risks ProtectionPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 314
• Est. completion date: April 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 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 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/day
Elobixibat 10 mg/day
• Elobixibat 5 mg/day
Elobixibat 5 mg/day
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Czech Republic,  Germany,  Hungary,  Mexico,  Poland,  Slovakia,  South Africa,  Sweden,  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 first 24 hours of treatment initiation	No
Secondary	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	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 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	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 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	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