The goal of this clinical trial is to evaluate if the study drug, CIN-103, can help reduce the symptoms associated with irritable bowel syndrome with predominant diarrhea (IBS-D) in adult patients. The main questions it aims to answer are: * To evaluate the efficacy of CIN-103 on symptoms of IBS-D when given to patients with IBS-D compared to a placebo. * To evaluate the safety and tolerability of CIN-103 when given to patients with IBS-D compared to a placebo Participants will attend the following visits: * Screening Period (1 Visit) * Baseline Period (1 Visit) * Will complete daily diary and other Patient Reported Outcomes (PROs) as described in the protocol to assess eligibility for continued participation. * 12-Week Treatment Period (5 Visits) * Study drug taken twice daily by mouth. * Will complete daily diaries and other PROs as described in the protocol. * Follow- Up Period (1 Visit) Researchers will compare CIN-103 Dose 1, CIN-103 Dose 2, and placebo, to evaluate the clinical response to multiple dose strengths of CIN-103 relative to placebo on abdominal pain and stool consistency along with safety and tolerability.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
421
Digestive Health Specialists - Dothan
Dothan, Alabama, United States
Clinical Research Associates, LLC
Huntsville, Alabama, United States
Elite Clinical Studies LLC
Phoenix, Arizona, United States
GI Alliance - Sun City
Sun City, Arizona, United States
Applied Research Center of Arkansas
Little Rock, Arkansas, United States
Occurrence of meeting Study Composite Responder status for an adult subject with IBS-D.
A subject is defined as a Study Composite Responder if he or she meets the Daily Composite Responder criteria for at least 50% of days with diary entry during the 12-week Double-Blind Treatment Period. A subject is defined as a Daily Composite Responder if he or she meets both the pain intensity and stool consistency criteria as follows: * Improvement in the mean daily worst abdominal pain (WAP) score by ≥ 30% compared to the mean daily WAP score from the Baseline Period (the average of the daily measurements over the 14 days prior to randomization); AND * Improvement in stool consistency based on the Bristol Stool Scale (BSS) score \< 5 or the absence of a bowel movement (BM) over the past 24 hours. Note: If a subject did not have a BM, an improvement of at least 30% in the WAP score is sufficient for a response on that day. The proportion of subjects with a primary outcome within each dose of CIN-103 will be compared to the proportion of subjects in the placebo arm.
Time frame: 12 weeks of Double Blind Treatment Period
The occurrence of meeting Weekly Composite Responder status
Time frame: 12-week of Double-Blind Treatment Period
The occurrence of meeting Weekly Composite Responder status over 4-weekly intervals (1 to 4, 5 to 8, and 9 to 12 weeks).
A subject is defined as a Weekly Composite Responder if he or she meets both abdominal pain and stool consistency criteria as follows: An Abdominal Pain Intensity Weekly Responder is defined as a subject who experiences a decrease in the weekly average of WAP in the past 24 hours score of at least 30% compared with Baseline; AND A Stool Consistency Weekly Responder is defined as a subject who experiences a 50% or greater reduction in the number of days per week with at least 1 stool that has a consistency of Type 6 or 7 compared with Baseline.
Time frame: 12 weeks of Double Blind Treatment Period
The change in a composite of the daily mean and weekly mean of daily WAP score and stool consistency score as compared to Baseline
The subject-reported WAP in the past 24 hours will be recorded on an 11-point (ie, 0 to 10) numeric rating scale, where 0 corresponds to no pain and 10 corresponds to worst imaginable pain. The stool consistency will be measured using the Bristol Stool Score, based on a 1 to 7 scale where 1 corresponds to a hard stool and 7 corresponds to watery diarrhea.
Time frame: 12-week of Double-Blind Treatment Period
The change in daily mean and weekly mean number of BMs per day compared to Baseline
Time frame: 12-week of Double-Blind Treatment Period
The occurrence of meeting Stool Consistency Responder status
A participant is considered a Stool Consistency Responder if there is an improvement in stool consistency based on the BSS score \< 5 or the absence of a bowel movement over the past 24 hours.
Time frame: 12-week of Double-Blind Treatment Period
The change in the daily mean and weekly mean of stool consistency measured with the Bristol Stool Scale (BSS) as compared to Baseline
The subject-reported BSS consistency score is based on a 1 to 7 scale where 1 corresponds to a hard stool and 7 corresponds to watery diarrhea.
Time frame: 12-week of Double-Blind Treatment Period
The occurrence of meeting Pain Responder status
A participant is considered a Pain Responder if there is an improvement in the mean daily WAP score by ≥ 30% compared to the mean daily WAP score from the Baseline Period (the average of the daily measurements over the 14 days prior to randomization).
Time frame: 12-week of Double-Blind Treatment Period
The change in the daily mean and weekly mean of daily WAP as compared to Baseline
Time frame: 12-week of Double-Blind Treatment Period
The change in the daily mean and weekly mean of daily abdominal bloating score as compared to Baseline.
The subject-reported abdominal bloating in the past 24 hours will be recorded on an 11-point (ie, 0 to 10) numeric rating scale, where 0 corresponds to no bloating and 10 corresponds to worst imaginable bloating.
Time frame: 12-week of Double-Blind Treatment Period
The change in the daily mean and weekly mean of daily urgency score compared to Baseline.
Daily urgency score is measured on a numeric rating scale from 0 (no urgency) to 10 (worst possible urgency).
Time frame: 12-week of Double-Blind Treatment Period
The change in daily mean and weekly mean number of fecal incontinence episodes compared to Baseline
Subjects will receive daily automatic reminders on eDiary to record the number of fecal incontinence episodes over the past 24 hours.
Time frame: 12-week of Double-Blind Treatment Period
Incidence of clinically significant changes, in the Investigator's opinion, in vital signs, physical examinations, ECGs, and clinical laboratory evaluations.
Including standard safety chemistry panel, hematology, coagulation, lipids, and urinalysis.
Time frame: Through study completion, up to 19 weeks.
Occurrence of Treatment-Emergent Adverse Events (TEAEs).
Time frame: Through study completion, up to 19 weeks.
Occurrence of treatment-emergent serious adverse events.
Time frame: Through study completion, up to 19 weeks.
Occurrence of TEAEs leading to premature discontinuation of the study drug.
Time frame: Through study completion, up to 19 weeks.
Occurrence of treatment-emergent clinically significant laboratory abnormalities.
Time frame: Through study completion, up to 19 weeks.
Percentage of post-randomization days with symptom of urgency present ("Yes")
The severity of bowel urgency will be captured on a numeric rating scale from 0 (no urgency) to 10 (worst possible urgency). Using this scale, bowel urgency will also be captured as not present "No" (score 0) or present "Yes" (score 1 to 10).
Time frame: 12-week of Double-Blind Treatment Period
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