Naldemedine Improves Patient-Reported Outcomes of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain in the COMPOSE Phase 3 Studies

Abstract

Michael Camilleri,1 Martin Hale,2 Bart Morlion,3 Jan Tack,4 Lynn Webster,5 James Wild6 1Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA; 2Gold Coast Research, LLC, Plantation, FL, USA; 3Leuven Center for Algology and Pain Management, University Hospital Leuven, University of Leuven, Leuven, Belgium; 4Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium; 5PRA Health Sciences, Salt Lake City, UT, USA; 6Upstate Clinical Research Associates, Williamsville, NY, USACorrespondence: Michael CamilleriClinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USATel [phone]Fax [phone]Email [email protected]: Opioid-induced constipation is among the most common side effects associated with opioid use in patients with chronic non-cancer pain, and it can have a significant negative impact on health-related quality of life (QOL). This analysis evaluated the effect of naldemedine 0.2 mg on patient-reported outcomes in three phase 3 clinical studies.Methods: COMPOSE-1 and COMPOSE-2 were identical randomized, double-blind, placebo-controlled, parallel-group studies of 12 weeks’ duration, allowing data to be integrated (n=1095). COMPOSE-3 was similar in design, but of 52 weeks’ duration (n=1241). Patients were adults with chronic non-cancer pain who had been treated with opioid analgesics for ≥ 3 months and experiencing opioid-induced constipation. Patient-reported outcomes included Patient Assessment of Constipation Symptoms (PAC-SYM; 12 questions assessed on a 5-point Likert scale), PAC-QOL (28 questions assessed on a 5-point Likert scale), and Subject Global Satisfaction (measured on a 7-point Likert scale). The proportion of patients achieving a ≥ 1.5 improvement in PAC-SYM and PAC-QOL was calculated. The correlation between change in PAC-SYM and PAC-QOL scores and frequency of bowel movements was also explored.Results: The proportion of PAC-SYM and PAC-QOL responders was significantly higher for naldemedine than for placebo at all assessed time points in COMPOSE-1/COMPOSE-2 (p< 0.005 for both) and COMPOSE-3 (p< 0.005 and p< 0.0001, respectively). There was a statistically significant correlation between improvement in PAC-SYM/PAC-QOL and frequency of bowel movements at all time points (p≤ 0.0002). The majority of patients treated with naldemedine reported markedly or moderately improved satisfaction with constipation and abdominal symptoms on the Subject Global Satisfaction questionnaire.Discussion: Naldemedine treatment was associated with a rapid and sustained clinically relevant improvement in patient-reported outcomes, indicating improvement in opioid-induced constipation-related symptoms and QOL.ClinicalTrials.gov Registration: NCT01965158, NCT01993940, NCT01965652.Keywords: gastrointestinal tract, minimal clinically important difference, mu opioid receptor, patient satisfaction, quality of life

Keywords

• gastrointestinal tract
• minimal clinically important difference
• mu opioid receptor
• patient satisfaction
• quality of life