S523 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of ANJ908, a Novel DGAT1 Inhibitor, in Patients With Chronic Idiopathic Constipation

Abstract

Introduction: Current treatment for chronic idiopathic constipation (CIC) is limited by: 1. Low magnitude of drug effect (increase of only ∼1-1.5 SBM per week) 2. Low overall response rate (typically < 20%) 3. Loss of efficacy within 3-6 months. Real-world experience where CIC patients often cycle through 2-4 pharmacotherapies shows the need for new medications with better efficacy. ANJ908 is a safe and well-tolerated diacylglycerol acyltransferase (DGAT) 1 inhibitor which increases bowel movement number and softens the stool in humans. We designed and conducted a phase 2 study of ANJ908 in CIC patients and present the data here for the first time. Methods: ANJ908C2102 was a multicenter, randomized, placebo-controlled, double-blind study designed to assess the efficacy and safety of ANJ908 in CIC patients. Patients meeting ROME IV diagnostic criteria for functional constipation (a.k.a. CIC) and had < 3 SBMs/week for prior the two weeks were eligible. Enrolled patients underwent a 2 week run-in period where all previous constipation treatment was stopped. After run-in, patients were randomized (1:1:1) to 4 weeks of once daily treatment with placebo, ANJ908 at 20 or 40 mg. Bowel movement timing, stool details, and patient reported constipation symptoms were recorded in an eDiary. Patient safety labs and AEs were monitored throughout the study. Results: A total of 191 patients were randomized. Patients were 77.9% female, with a mean (SD) age and BMI of 42.2 (14.4) years and 23.2 (4.36) kg/m2, respectively. ANJ908 increased the mean (SE) placebo-subtracted number of SBM/week by +2.28 (0.75; p = 0.0027) and +3.10 (0.74; p < 0.0001) and CSBM/week by +1.53 (0.70; p = 0.03) and +1.81 (0.70; p = 0.01), respectively at week 4. ANJ908 improved stool consistency, provided constipation relief, decreased straining severity, and reduced rescue medication use. ANJ908 was safe and generally well tolerated. Mild diarrhea, nausea and vomiting were the most common AEs with a total of 7 (out of 64) patients in the ANJ908 20 mg group discontinuing treatment due to AEs. Conclusion: ANJ908 demonstrated increases in weekly SBMs and CSBMs to a magnitude greater than previous treatments. Furthermore, ANJ908 improved patient reported stool consistency and relief of constipation symptoms. The benefit-risk profile of ANJ908 justifies advancement into phase 3 clinical development to confirm its efficacy and safety. If this profile is confirmed, ANJ908 may become a treatment better able to address the unmet need in CIC patients.