Trial Outcomes & Findings for Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation (NCT NCT01895543)

NCT ID: NCT01895543

Last Updated: 2016-05-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 411 participants
• Primary outcome timeframe: For the overall 52-week Treatment Period
• Results posted on: 2016-05-09

Participant Flow

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

Participant milestones

Measure	EBX10 Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Overall Study STARTED	411
Overall Study Safety Analysis Set	409
Overall Study Per Protocol Analysis Set	380
Overall Study COMPLETED	282
Overall Study NOT COMPLETED	129

Reasons for withdrawal

Measure	EBX10 Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Overall Study Withdrawal by Subject	43
Overall Study Lost to Follow-up	25
Overall Study Adverse Event	28
Overall Study Subject's substantial non-compliance	6
Overall Study Protocol Violation	1
Overall Study Physician Decision	2
Overall Study Other (Not fulfilling above criteria)	24

Baseline Characteristics

Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation

Baseline characteristics by cohort

Measure	EBX10 n=411 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	362 Participants n=5 Participants
Age, Categorical >=65 years	49 Participants n=5 Participants
Age, Continuous	48.6 Years STANDARD_DEVIATION 14.13 • n=5 Participants
Sex: Female, Male Female	351 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	74 Participants n=5 Participants
Race (NIH/OMB) White	324 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Height	1.654 Meters (m) STANDARD_DEVIATION 0.0834 • n=5 Participants
Weight	73.61 Kilogram (Kg) STANDARD_DEVIATION 14.159 • n=5 Participants
Body Mass Index (BMI)	26.87 Kg/m^2 STANDARD_DEVIATION 4.284 • n=5 Participants

PRIMARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

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.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	241 Patients
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	14 Patients

PRIMARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

Outcome measure include laboratory parameters from haematology, coagulation and clinical chemistry

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Gamma Glutamyl Transferase (Units/Litre): >3*ULN	6 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Triglycerides : >3.39 millimoles/Litre	5 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables LDL Cholesterol : >4.1 millimoles/Litre	3 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Glucose : <2.2 (F) and <2.8 (M) millimoles/Litre	3 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Activated Partial Thromboplastin Time : >70 second	3 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Prothrombin Time : >25 seconds	2 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Sodium : >155 millimoles/Litre	2 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Chloride : <90 millimoles/Litre	2 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Alanine Aminotransferase : >3*ULN	1 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Erythrocytes (10^12/L) : <3.1	1 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Potassium : >6.5 millimoles/Litre	1 Patients
Incidence of Markedly Abnormal Changes in Clinical Safety Laboratory Variables Glucose : >22.2 millimoles/Litre	1 Patients

PRIMARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

A routine 12-lead ECG was performed at all visits. The ECG included heart rate, PR, QRS, and QT intervals assessment.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Incidence of Markedly Abnormal Changes in Electrocardiograms (ECGs)	3 Patients

PRIMARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

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.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs Temperature - <35^0 celsius	2 Patients
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs Diastolic BP - >105 mmHg	2 Patients
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs Diastolic BP - <50 mmHg	1 Patients
Incidence of Markedly Abnormal Changes in Body Weight and Vital Signs Systolic BP - <85 mmHg	1 Patients

PRIMARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

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.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Number of Patients Using Concomitant Medications	340 Patients

SECONDARY outcome

Timeframe: For the overall 52-week Treatment Period

Population: Safety Analysis Set

The use of OTC laxatives during the trial was assessed based upon the concomitant medication module of the electronic Case Report Form (eCRF).

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Use of Concomitant Over-the-counter (OTC) Laxatives Contact laxatives	33 Patients
Use of Concomitant Over-the-counter (OTC) Laxatives Osmotically acting laxatives	14 Patients
Use of Concomitant Over-the-counter (OTC) Laxatives Softeners, Emollients	11 Patients
Use of Concomitant Over-the-counter (OTC) Laxatives Bulk Producers	6 Patients
Use of Concomitant Over-the-counter (OTC) Laxatives Enemas	1 Patients

SECONDARY outcome

Timeframe: At Week 12, 24, 36, and 52

Population: Safety Analysis Set

The constipation severity score was measured on a 5-point scale (1: none to 5: very severe).

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Change From Baseline in Global Evaluation of Constipation Severity At Week 12	-0.2 Unit on a scale Standard Deviation 1.10
Change From Baseline in Global Evaluation of Constipation Severity At Week 24	-0.2 Unit on a scale Standard Deviation 1.10
Change From Baseline in Global Evaluation of Constipation Severity At Week 36	-0.1 Unit on a scale Standard Deviation 1.11
Change From Baseline in Global Evaluation of Constipation Severity At Week 52	-0.2 Unit on a scale Standard Deviation 1.08

SECONDARY outcome

Timeframe: At Week 12, 24, 36, and 52

Population: Safety Analysis Set

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).

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Change From Baseline in Global Evaluation of Treatment Effectiveness At Week 12	-0.6 Unit on a scale Standard Deviation 1.43
Change From Baseline in Global Evaluation of Treatment Effectiveness At Week 24	-0.6 Unit on a scale Standard Deviation 1.36
Change From Baseline in Global Evaluation of Treatment Effectiveness At Week 36	-0.7 Unit on a scale Standard Deviation 1.24
Change From Baseline in Global Evaluation of Treatment Effectiveness At Week 52	-0.7 Unit on a scale Standard Deviation 1.22

SECONDARY outcome

Timeframe: At Week 12, 24, 36 and 52

Population: Safety Analysis Set

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'.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score At Week 12	-0.24 Unit on a scale Standard Deviation 0.677
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score At Week 24	-0.21 Unit on a scale Standard Deviation 0.639
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score At Week 36	-0.16 Unit on a scale Standard Deviation 0.687
Change From Baseline in Patient Assessment of Constipation - Quality of Life (PAC-QOL): Overall Score At Week 52	-0.22 Unit on a scale Standard Deviation 0.644

SECONDARY outcome

Timeframe: At Week 12, 24, 36 and 52

Population: Safety Analysis Set

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.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores At Week 12	0.0 Unit on a scale Standard Deviation 0.14
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores At Week 36	0.0 Unit on a scale Standard Deviation 0.15
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores At Week 24	0.0 Unit on a scale Standard Deviation 0.14
Change From Baseline in EuroQol Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Scores At Week 52	0.0 Unit on a scale Standard Deviation 0.15

SECONDARY outcome

Timeframe: At Week 12, 24, 36 and 52

Population: Safety Analysis Set

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.

Outcome measures

Measure	EBX10 n=409 Participants Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score At Week 36	1.0 Unit on a scale Standard Deviation 12.44
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score At Week 52	0.8 Unit on a scale Standard Deviation 12.35
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score At Week 12	0.7 Unit on a scale Standard Deviation 13.43
Change From Baseline in EuroQol Group Visual Analog Scale (EQ-VAS) Score At Week 24	1.2 Unit on a scale Standard Deviation 11.95

Adverse Events

EBX 10

Serious events: 14 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Measure	EBX 10 n=409 participants at risk Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Blood and lymphatic system disorders Anaemia	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Gastrointestinal disorders Constipation	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
General disorders Non-cardiac chest pain	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Infections and infestations Appendicitis	0.49% 2/409 • Number of events 2 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Infections and infestations Breast abscess	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Infections and infestations Urinary tract infection	0.24% 1/409 • Number of events 2 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangioma	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Nervous system disorders Carpal tunnel syndrome	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Psychiatric disorders Emotional distress	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Renal and urinary disorders Nephrolithiasis	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Vascular disorders Aortic dissection	0.24% 1/409 • Number of events 1 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.

Other adverse events

Measure	EBX 10 n=409 participants at risk Elobixibat 10 mg Elobixibat 10 mg: 10 mg Elobixibat daily, with possibility for dose adjustment to 5 mg daily.
Gastrointestinal disorders Abdominal pain	6.8% 28/409 • Number of events 31 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.
Gastrointestinal disorders Diarrhoea	13.9% 57/409 • Number of events 69 • For the overall 52-week Treatment Period and the 2-week Follow-up Period 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 . Information on AEs was collected at each trial visit.

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: DK0-Disclosure@ferring.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
• Publication restrictions are in place

Restriction type: OTHER