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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01895543

Enrollment

411

Registered

2013-07-10

Start date

2013-09-30

Completion date

2015-05-31

Last updated

2016-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Idiopathic Constipation

Brief summary

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

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).

Interventions

DRUGElobixibat 10 mg

10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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* The patient has been withdrawn/discontinued from the 000079 or 000080 trials.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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)	For the overall 52-week Treatment Period	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.
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables	For the overall 52-week Treatment Period	Outcome measure include laboratory parameters from haematology, coagulation and clinical chemistry
Incidence of Markedly Abnormal Changes in Electrocardiograms (ECGs)	For the overall 52-week Treatment Period	A routine 12-lead ECG was performed at all visits. The ECG included heart rate, PR, QRS, and QT intervals assessment.
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs	For the overall 52-week Treatment Period	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.
Number of Patients Using Concomitant Medications	For the overall 52-week Treatment Period	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.

Secondary

Measure	Time frame	Description
Use of Concomitant Over-the-counter (OTC) Laxatives	For the overall 52-week Treatment Period	The use of OTC laxatives during the trial was assessed based upon the concomitant medication module of the electronic Case Report Form (eCRF).
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score	At Week 12, 24, 36 and 52	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.
Change From Baseline in Global Evaluation of Constipation Severity	At Week 12, 24, 36, and 52	The constipation severity score was measured on a 5-point scale (1: none to 5: very severe).
Change From Baseline in Global Evaluation of Treatment Effectiveness	At Week 12, 24, 36, and 52	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).
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score	At Week 12, 24, 36 and 52	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'.
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores	At Week 12, 24, 36 and 52	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.

Countries

Belgium, Canada, Czechia, Hungary, Poland, Slovakia, South Africa, Sweden, United Kingdom, United States

Participant flow

Recruitment details

The trial enrolled patients from two lead-in, double-blind efficacy trials (000079 and 000080).

Participants by arm

Arm	Count
EBX10 Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.	411
Total	411

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	28
Overall Study	Lost to Follow-up	25
Overall Study	Other (Not fulfilling above criteria)	24
Overall Study	Physician Decision	2
Overall Study	Protocol Violation	1
Overall Study	Subject's substantial non-compliance	6
Overall Study	Withdrawal by Subject	43

Baseline characteristics

Characteristic	EBX10
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	49 Participants
Age, Categorical Between 18 and 65 years	362 Participants
Age, Continuous	48.6 Years STANDARD_DEVIATION 14.13
Body Mass Index (BMI)	26.87 Kg/m^2 STANDARD_DEVIATION 4.284
Height	1.654 Meters (m) STANDARD_DEVIATION 0.0834
Race (NIH/OMB) American Indian or Alaska Native	2 Participants
Race (NIH/OMB) Asian	10 Participants
Race (NIH/OMB) Black or African American	74 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	324 Participants
Sex: Female, Male Female	351 Participants
Sex: Female, Male Male	60 Participants
Weight	73.61 Kilogram (Kg) STANDARD_DEVIATION 14.159

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	77 / 409
serious Total, serious adverse events	14 / 409

Outcome results

Primary

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.

Time frame: For the overall 52-week Treatment Period