TY - JOUR
T1 - Naldemedine improves patient-reported outcomes of opioid-induced constipation in patients with chronic non-cancer pain in the compose phase 3 studies
AU - Camilleri, Michael
AU - Hale, Martin
AU - Morlion, Bart
AU - Tack, Jan
AU - Webster, Lynn
AU - Wild, James
N1 - Publisher Copyright:
© 2021 Camilleri et al.
PY - 2021
Y1 - 2021
N2 - 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, placebocontrolled, 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 opioidinduced constipation-related symptoms and QOL. ClinicalTrials.gov Registration: NCT01965158, NCT01993940, NCT01965652.
AB - 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, placebocontrolled, 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 opioidinduced constipation-related symptoms and QOL. ClinicalTrials.gov Registration: NCT01965158, NCT01993940, NCT01965652.
KW - Gastrointestinal tract
KW - Minimal clinically important difference
KW - Mu opioid receptor
KW - Patient satisfaction
KW - Quality of life
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U2 - 10.2147/JPR.S282738
DO - 10.2147/JPR.S282738
M3 - Article
AN - SCOPUS:85111382012
SN - 1178-7090
VL - 14
SP - 2179
EP - 2189
JO - Journal of Pain Research
JF - Journal of Pain Research
ER -