Clinical Trial Results:
A Multicenter, Open-label, Safety and Tolerability Extension Trial of 5 mg and 10 mg Elobixibat Daily in the Treatment of Chronic Idiopathic Constipation
|
Summary
|
|
EudraCT number |
2012-005601-46 |
Trial protocol |
BE SE SK HU CZ GB PL |
Global end of trial date |
13 May 2015
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
26 May 2016
|
First version publication date |
26 May 2016
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
000081
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01895543 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Ferring International Pharmascience Center US, Inc.
|
||
Sponsor organisation address |
100 Interpace Parkway, Parsippany, NJ, United States, 07054
|
||
Public contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
|
||
Scientific contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
04 Jun 2015
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
13 May 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 May 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Safety and Tolerability Extension Trial for Patients with Chronic Idiopathic Constipation (CIC)
|
||
Protection of trial subjects |
Before obtaining the consent from patients, the Investigator appropriately explained the aims, methods, anticipated benefits, potential hazards, and any other aspects of the trial which are relevant to the patient’s decision to participate, in a language understood by the patient. The Investigator explained to the patients about their right of freedom to refuse to enter the trial or to withdraw from it at any time, without any consequences on their further care and without the need to justify their decision. The trial was conducted in accordance with the Declaration of Helsinki and in compliance with the International Conference on Harmonization-Good Clinical Practice guidelines.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Sep 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 17
|
||
Country: Number of subjects enrolled |
Belgium: 6
|
||
Country: Number of subjects enrolled |
Czech Republic: 10
|
||
Country: Number of subjects enrolled |
Hungary: 34
|
||
Country: Number of subjects enrolled |
Poland: 10
|
||
Country: Number of subjects enrolled |
Slovakia: 12
|
||
Country: Number of subjects enrolled |
South Africa: 30
|
||
Country: Number of subjects enrolled |
Sweden: 4
|
||
Country: Number of subjects enrolled |
United Kingdom: 38
|
||
Country: Number of subjects enrolled |
United States: 250
|
||
Worldwide total number of subjects |
411
|
||
EEA total number of subjects |
114
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
362
|
||
From 65 to 84 years |
49
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||
Recruitment details |
The trial enrolled patients from two lead-in, double-blind efficacy trials (000079 and 000080). | ||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||
Screening details |
Enrolled patient (with CIC) completed at least 12 weeks of double-blind treatment in either of the lead-in efficacy trials (Trial codes 000079 or 000080). The patients agreed to refrain from making any new, major life-style changes that may affect CIC symptoms from the time of signing the informed consent form through to the last trial visit. | ||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||
|
Arm title
|
EBX10 | ||||||||||||||||||||||
Arm description |
Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Elobixibat
|
||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||
Other name |
|||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||
Dosage and administration details |
10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EBX10
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
EBX10
|
||
Reporting group description |
Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily. | ||
Subject analysis set title |
Per Protocol Analysis Set
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Set included all enrolled patients who had no major protocol deviations and included 380 patients.
|
||
Subject analysis set title |
Safety Analysis Set
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Set included all enrolled patients who took at least one dose of Investigational Medicinal Product (IMP) and included 409 patients.
|
||
|
|||||||||||
End point title |
Number of patients with adverse events (AEs) and serious adverse events (SAEs) [1] | ||||||||||
End point description |
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 and recorded at each visit. The data are presented for the Safety Analysis Set.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The data were presented using descriptive statistics. No statistical analysis was performed. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Incidence of markedly abnormal changes in clinical safety laboratory variables [2] | ||||||||||||||||||||||||||||||
End point description |
Outcome measure include laboratory parameters from haematology, coagulation and clinical chemistry. The data are presented for the Safety Analysis Set.
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||||||||||||||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The data were presented using descriptive statistics. No statistical analysis was performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||
End point title |
Incidence of markedly abnormal changes in electrocardiograms (ECGs) [3] | ||||||
End point description |
A routine 12-lead ECG was performed at all visits. The ECG included heart rate, PR, QRS, and QT intervals assessment. The data are presented for the Safety Analysis Set.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The data were presented using descriptive statistics. No statistical analysis was performed. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||
End point title |
Incidence of markedly abnormal changes in body weight and vital signs [4] | ||||||||||||||
End point description |
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. The data are presented for the Safety Analysis Set.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||||||||||
| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The data were presented using descriptive statistics. No statistical analysis was performed. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||
End point title |
Number of patients using concomitant medications [5] | ||||||
End point description |
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. The data are presented for the Safety Analysis Set.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||
| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The data were presented using descriptive statistics. No statistical analysis was performed. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||
End point title |
Use of concomitant over-the-counter (OTC) laxatives | ||||||||||||||||
End point description |
The use of OTC laxatives during the trial was assessed based upon the concomitant medication module of the electronic Case Report Form (eCRF). The data are presented for the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
For the overall 52-week Treatment Period
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline in global evaluation of constipation severity | ||||||||||||||||
End point description |
The constipation severity score was measured on a 5-point scale (1: none to 5: very severe). The data are presented for the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At Week 12, 24, 36, and 52
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline in global evaluation of treatment effectiveness | ||||||||||||||||
End point description |
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). The data are presented for the the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At Week 12, 24, 36, and 52
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline in Patient assessment of constipation - Quality of Life (PAC-QOL): Overall score | ||||||||||||||||
End point description |
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’. The data are presented for the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At Week 12, 24, 36 and 52
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) scores | ||||||||||||||||
End point description |
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. The data are presented for the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At Week 12, 24, 36 and 52
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) score | ||||||||||||||||
End point description |
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. The data are presented for the Safety Analysis Set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At Week 12, 24, 36 and 52
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
For the overall 52-week Treatment Period and the 2-week Follow-up Period
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The Investigator monitored the condition of the patient and recorded all AEs throughout the trial from the time of obtaining informed consent until the last visit (i.e. Visit 6 - the end of the follow-up period) in the AEs Log . During the trial, a total of 26 patients were down-titrated to 5 mg a day and most of these had diarrhea.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EBX 10
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
19 Nov 2013 |
The majority of the changes in this amendment were clarifications to the initial protocol (dated 21 Feb 2013 in all participating countries except in the UK where the original protocol was dated 24 May 2013). The changes included e.g. adjustments of secondary analyses and endpoints, adjustment of exclusion criteria, clarification of administration and documentation of first IMP intake, and correction of wording and minor errors.
This amendment was applicable for all sites. |
||
24 Feb 2014 |
The main change in this amendment was the updated inclusion and exclusion criteria following the termination of the lead in efficacy trials (Echo 1 and Echo 2; protocols 000079 and 000080, respectively), to allow eligible patients to roll over into this trial (Echo 3) at the earliest convenience, and without interruption of treatment. Amendment 3 for South Africa corresponds to amendment 2 for all other participating countries.
This amendment was applicable for all sites in South Africa. |
||
12 Sep 2014 |
The main change in this amendment was the updated recruitment projections for this trial due to Sponsor's early termination of the lead in efficacy trials (Echo 1 and Echo 2; protocols 000079 and 000080, respectively) that significantly lowered the number of potential patients who could roll over into this trial.
This amendment was applicable for all sites. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
