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

Abstract

OBJECTIVE:

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.

CLINICALTRIALSGOV REGISTRATION:

NCT01965158, NCT01993940, NCT01965652.

• Authors: Michael Camilleri, Martin Hale, Bart Morlion, Jan Tack, Lynn Webster, James Wild
• Journal: Journal of pain research (J Pain Res) Vol. 14 Pg. 2179-2189 ( 2021) ISSN: 1178-7090 [Print] New Zealand
• PMID: 34295186 (Publication Type: Journal Article)
• Copyright: © 2021 Camilleri et al.