Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation

Study Overview
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Brief Summary
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Safety and Tolerability Extension Trial for Patients with Chronic Idiopathic Constipation (CIC)

Detailed Description
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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).

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

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Drug: Elobixibat 10 mg


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: The patient has been withdrawn/discontinued from the 000079 or 000080 trials.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: Transdermal patch Established use of oral, injected or implanted hormonal methods of contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS). Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBX10<br>Elobixibat 10 mg | Drug: Elobixibat 10 mg<br>* 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.<br>|

What is the study measuring?
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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 |