A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome

Overall responder was a participant who has at least 7 evaluable weeks of data and has reported an improvement in their weekly symptoms (abdominal pain intensity [API] and stool frequency [SF] or consistency [SC]) for greater than or equal to (>=) 50 percent (%) of the treatment period. Improvement for abdominal pain intensity was defined as decrease in weekly average of worst abdominal pain in the past 24 hours score of at least 30% compared with baseline for Cohort C and Cohort D, for stool frequency was defined as increase of 1 or more complete spontaneous bowel movements (CSBM) per week compared with baseline for Cohort C and for stool consistency was defined as decrease at least 50% in the proportion of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline for Cohort D. Participants with <4 weeks available were considered non-responders.

An adverse event (AE) was any untoward medical occurrence in a participant administered study medication and which does not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened in severity on or after the start date of the study treatment and includes all AEs recorded through the follow-up visit. A treatment-related TEAE was a TEAE possibly related to the study treatment.

The subject global assessment of relief was collected weekly through the electronic clinical outcome assessment (eCOA) system. It was a comparison of how the participant has felt over the past week with regards to their IBS to the way they felt before entering the study. It was measured on a 5-point Likert scale with the following responses: Completely relieved; considerably relieved; somewhat relieved; unchanged; worse. The total score ranged from 0-20, where higher scores indicated worsening of condition.

Stool consistency of each bowel movement was rated on 7-level Bristol Stool Chart where Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score range of 1 to 7 where, 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Change in percentage of days per week with at least 1 stool with a undesired stool consistency of 1 or 2 for Cohort C and 6 or 7 for Cohort D on the Bristol Stool Chart from baseline at Week 1, 4, 8, Follow-up Visit (Week 12, 13 and 14) was reported.

Stool consistency of each bowel movement was assessed by participants using the 7-point BSFS from 1 to 7 where Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Lower numbers represented more formed stools and higher numbers represented less formed stools. A negative change from Baseline indicates improvement.

Stool frequency was defined as a sum of weekly CSBMs. Participants were reminded to rate all their bowel movements in the Bristol Stool Chart (BSC) before answering the question. Stool types were assessed using the 7-point BSFS where 1 = separate hard lumps, like nuts (hard to pass), 2 = sausage-shaped but lumpy, 3 = like a sausage but with cracks on the surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges (passed easily), 6 = fluffy pieces with ragged edges, a mushy stool, 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Weekly stool frequency was based on the daily stool frequency which was calculated as follows: if there was 1 or more entry for BSC, the number of BSC entries was summed up. If on that day laxative was used, the daily stool frequency was set to 0. If an answer to CSBMs, but no BSC entry was provided, the daily stool frequency was set to 0 on that day.

Participants were asked to complete a QOL of 34 items which formed 8 scales: dysphoria (8 items), interference with activity (7 items), body image (4 items), health worry (3 items), food avoidance (3 items), social reaction (4 items), sexual (2 items), and relationships (3 items). All 8 scales were rated on a five-point response scale where, 1= not at all, 2= slightly, 3= moderately, 4= quite a bit, 5= extremely or a great deal. Scores for individual items were averaged to obtain a total score for each sub-scale of IBSQoL. Total and subscale scores were transformed to a 0 to 100 point scale (0=lowest score, 100=highest possible score) with higher scores indicating better IBS-specific quality of life. Transformed scale score = (Sum of the items-lowest possible score/Possible raw score range)∗100. A positive change from baseline indicates improved quality of life.

Participants were asked to complete a questionnaire on the severity of abdominal distension and pain, frequency of abdominal pain, dissatisfaction with bowel habits, and interference of IBS symptoms with daily life. The IBS-SSS was measured on a Visual Analog Scale (VAS scale) in combination with reported numeric values which equated to an overall score. The scale range was from 0 (no symptoms) to 500 (maximum severity). Participants were categorized as having mild (74-174), moderate (175-299), or severe (>300) IBS symptoms based on symptomology. Higher scores were indicative of greater disease severity (worse outcome). A negative change from Baseline indicates improvement.

Participants were asked to complete the HADS which was a 14-item scale (7 items- anxiety and 7 items-depression) that generated ordinal data. Each question was rated on a scale from 0 - 3. The outcome of the HADS questionnaire was two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression. A negative change from Baseline indicates improvement.