Phase 2 Randomized, Double‑Blind, Placebo‑Controlled Study of Brenipatide (LY3537031) for Efficacy and Safety in Adults with Irritable Bowel Syndrome‑Constipation

The primary objective is to assess the efficacy of Irritable Bowel Syndrome-Constipation treatment with brenipatide compared with placebo, measured by the proportion of participants achieving a weekly composite clinical response during weeks 9 through 16; this endpoint evaluates clinically meaningful improvement in bowel habit normalization and abdominal symptom relief, which are central to disease management.

The trial enrolled 272 adult participants of both sexes who satisfied the Rome IV criteria for Irritable Bowel Syndrome - Constipation, including a predominance of Bristol Stool Form Scale Types 1 or 2 in more than 25 % of bowel movements and fewer than 25 % of Types 6 or 7. Eligibility required an average worst abdominal pain score of ≥3.0 on a 0‑to‑10 scale recorded over 14 consecutive days during the screening period. Participants were selected from a general adult population without reported restrictions on diet, physical activity, or other lifestyle habits, and were classified as patients with the target condition. Key inclusion criteria focused on the diagnostic and symptom severity thresholds, while no additional exclusion details were provided.

The study is a Phase 2, randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of Brenipatide (LY3537031) in adult participants with Irritable Bowel Syndrome-Constipation. Approximately 200 participants will undergo a screening visit lasting up to 2 weeks to confirm Rome IV criteria and a minimum worst abdominal pain score of ≥3.0; eligible individuals will be randomized 1:1 to receive subcutaneous Brenipatide or matching placebo. Study medication will be administered weekly for 16 weeks, with scheduled clinic visits at baseline (randomization), weeks 4, 8, 12, and the end‑of‑study visit at week 16 to collect efficacy assessments, safety laboratory data, and eDiary entries. The primary endpoint is the percentage of participants achieving a weekly composite clinical response in at least 50 % of weeks 9–16. Participant involvement therefore spans the screening period plus 16 weeks of treatment. Early termination may occur due to serious adverse events, lack of protocol compliance, withdrawal of consent, or investigator‑determined clinical necessity.

The investigational product Brenipatide is supplied as a solution for injection in a pre‑filled syringe for subcutaneous administration. The formulation contains the active substance ly3537031. Each dose is prepared according to the protocol‑specified volume, and the injection is performed by subcutaneous route. Dosing frequency and duration are defined in the study schedule and are identical for all participants receiving the active agent.

The control arm receives a matching placebo formulated to resemble the active product in appearance and packaging. The placebo is administered by the same subcutaneous route and follows the identical dosing schedule as the investigational product to maintain blinding.

All study injections are administered in a clinical setting by qualified personnel. Dosing intervals are recorded in the case report form, and adherence is monitored through site‑generated logs and participant diaries. Compliance checks include verification of injection site, timing, and documentation of any missed doses.

The primary efficacy endpoint is the Weekly Composite Clinical Response, defined as the proportion of participants who achieve a composite clinical response for at least 50 % of the evaluated weeks. This endpoint is assessed for each participant during the weekly observation period spanning weeks 9 through week 16.

Efficacy data are collected at each weekly visit within the specified interval. The proportion of responders is calculated for each treatment arm and compared between the Brenipatide and placebo groups using statistical methods appropriate for binary outcomes. Summaries will include the percentage of participants meeting the response criterion and confidence intervals for the treatment effect.