Previously reported study results have demonstrated that methylnaltrexone is a selective mu-opioid receptor antagonist that rapidly induced laxation without affecting central analgesia. The purpose of the current analysis was to examine the effect of methylnaltrexone on patient-reported and clinician-reported Global Clinical Impression of Change (GCIC) in bowel status.

Material and Methods

In this randomized, double-blind placebo-controlled trial, 134 patients with OIC were treated with placebo or methylnaltrexone (0.15mg/kg SC QOD dosing) for 2 weeks. The protocol and informed-consent forms received independent IRB approval. Patients and clinicians reported their assessment of change in bowel status on Day 7 and Day 14 after start of therapy using a 7-point Likert scale

(1= Much worse, 7=Much better). Patients assessed constipation distress using a 5-point Likert scale (1= None, 5= Very much) at baseline, Day 7 and Day 14. GCIC scores were compared between methylnaltrexone and placebo using ANOVA. Correlation coefficients were estimated between the GCIC and change in constipation distress scores.

Results

The mean patient and clinician reported GCIC scores were significantly greater (p<0.001) in the methylnaltrexone group compared to the placebo group on Day 7 (patient: 5.6±1.2 vs. 4.6±1.2; clinician: 5.5±1.2 vs. 4.5±1.0) and Day 14 (patient: 5.6±1.4 vs. 4.7±1.1;clinician: 5.6±1.4 vs. 4.6 ±1.0). The correlation between the change in constipation distress and the GCIC scores in the methylnaltrexone and placebo groups on Day 7 (patient: r = –0.54 vs. –0.41;clinician: r = –0.42 vs. –0.33) and Day 14 (patient: r = –0.62 vs. –0.32; clinician: r = –0.55 vs. –0.36) were found to be significant, with a stronger association between measures in the methylnaltrexone group compared to placebo.

Conclusions

In this study, methylnaltrexone showed a significant positive effect on bowel status in advanced illness patients with opioid-induced constipation as reflected by the patient-reported and clinician-reported GCIC scores.