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

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ClinicalTrials.gov Identifier: NCT01833065
Recruitment Status : Terminated (Terminated due to a distribution issue with the trial medication)
First Posted : April 16, 2013
Results First Posted : October 20, 2015
Last Update Posted : October 20, 2015
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

April 12, 2013
April 16, 2013
July 17, 2015
October 20, 2015
October 20, 2015
April 2013
March 2014   (Final data collection date for primary outcome measure)
Overall Complete Spontaneous Bowel Movement (CSBM) Response [ Time Frame: During the first 12 weeks ]
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.
Overall Complete Spontaneous Bowel Movement (CSBM) Response [ Time Frame: At 12 weeks ]
Complete list of historical versions of study NCT01833065 on ClinicalTrials.gov Archive Site
  • Occurrence of CSBM Response [ Time Frame: Within first 24 hours of treatment initiation ]
    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').
  • Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs) [ Time Frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period ]
    The change from Baseline for the continuous variable was estimated using a repeated measures analysis of covariance (ANCOVA) model.
  • Change From Baseline in Weekly Stool Consistency of SBMs [ Time Frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period ]

    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.

  • Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder [ Time Frame: At Week 12 ]

    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.

  • Change From Baseline in Weekly Degree of Straining of SBMs [ Time Frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period ]

    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.

  • Change From Baseline in Weekly Abdominal Bloating Score [ Time Frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period ]

    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.

  • Change From Baseline in Weekly Abdominal Discomfort Score [ Time Frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period ]

    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.

  • Occurrence of CSBM Response [ Time Frame: Within 24 hours of treatment initiation ]
  • Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs) [ Time Frame: For the overall 12-week Treatment Period ]
  • Change From Baseline in Weekly Stool Consistency of SBMs [ Time Frame: For the overall 12-week Treatment Period ]
  • Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder [ Time Frame: At Week 12 ]
  • Change From Baseline in Weekly Degree of Straining of SBMs [ Time Frame: For the overall 12-week Treatment Period ]
  • Change From Baseline in Weekly Abdominal Bloating Score [ Time Frame: For the overall 12-weekTreatment Period ]
  • Change From Baseline in Weekly Abdominal Discomfort Score [ Time Frame: For the overall 12-week Treatment Period ]
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Chronic Idiopathic Constipation
  • Drug: Elobixibat 10 mg/day
    Elobixibat 10 mg/day
    Other Name: A3309
  • Drug: Elobixibat 5 mg/day
    Elobixibat 5 mg/day
    Other Name: A3309
  • Drug: Placebo
    Placebo
  • Experimental: EBX 10
    Elobixibat 10 mg/day
    Intervention: Drug: Elobixibat 10 mg/day
  • Experimental: EBX 5
    Elobixibat 5 mg/day
    Intervention: Drug: Elobixibat 5 mg/day
  • Placebo Comparator: PLCBO
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
314
840
April 2014
March 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Brazil,   Canada,   Czech Republic,   Germany,   Hungary,   Mexico,   Poland,   Slovakia,   South Africa,   Sweden,   United Kingdom,   United States
 
 
NCT01833065
000080
2012-005588-28 ( EudraCT Number )
No
Not Provided
Not Provided
Ferring Pharmaceuticals
Ferring Pharmaceuticals
Not Provided
Study Director: Clinical Development Support Ferring Pharmaceuticals
Ferring Pharmaceuticals
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP