Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation

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 measure include laboratory parameters from haematology, coagulation and clinical chemistry

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

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

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

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).

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'.

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 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.