Webster, L., Jansen, J.P., Peppin, J., Lasko, B., Irving, G., Morlion, B., . . . Carter, E. (2008). Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain, 137, 428–440.

DOI Link

Study Purpose

To assess the effectiveness and safety of alvimopan, a peripherally acting mu-opioid receptor antagonist, in patients with noncancer pain and opioid-induced bowel dysfunction.

Intervention Characteristics/Basic Study Process

Patients were randomized to one of four groups: oral alvimopan 0.5 mg twice daily (n = 130), oral alvimopan 1 mg daily (n = 133), oral alvimopan 1 mg twice daily (n = 130), or placebo capsules (n = 129).

Patients were instructed to discontinue laxative use. Rescue laxative medication (bisacodyl 10-30 mg) could be taken if the patient experienced discomfort with no bowel movement (BM) for four consecutive days. An interactive voice response system via touch-tone telephone was used for number of BMs, associated symptoms, rescue laxative use, opioid consumption, and pain intensity.

Sample Characteristics

  • The study reported on a final sample of 333 patients aged 18 years or older.
  • Mean patient age was 49.7 years in the alvimopan 0.5-mg twice daily group, 51.5 years in the alvimopan 1-mg daily group, 48.6 years in the alvimopan 1-mg twice daily group, and 51.3 years in the placebo group. 
  • The sample was 64% female and 36% male.
  • Patients had noncancer pain and an opioid regimen equivalent to at least 30 mg of oral morphine for at least one month prior to screening.
  • Back pain was the primary pain condition.
  • Patients with neuralgia, fibromyalgia, arthritis, joint pain, and headache were also included.

Setting

  • Multi-site
  • Patients' homes and 113 centers in 9 countries

Study Design

This was a phase IIb, randomized, double-blind, placebo-controlled, parallel-group study.

Measurement Instruments/Methods

  • Patient Assessment of Constipation Symptoms (PAC-SYM)
  • Patient Assessment of Constipation Quality of Life (PAC-QOL)
  • Numeric Pain Scale (0 = no pain; 10 = worse possible pain)
  • Modified Himmelsbach Withdrawal Scale to measure signs of withdrawal

Results

  • Change in frequency of spontaneous bowel movements (SBMs) during the first three weeks of the treatment period was greater in all alvimopan groups versus the placebo group (p < 0.001).
  • Mean weekly frequency of SBMs was significantly greater during the treatment period for all alvimopan groups versus the placebo group (p ≤ 0.01), as was the overall mean change in SBMs (p < 0.001).
  • On the first day of treatment, 31% of patients in each alvimopan group had at least one SBM, compared with 18% in the placebo group (p < 0.05).
  • Seventy-seven percent of patients in the alvimopan 0.5-mg twice daily group and 75% in both the 1-mg daily group and the 1-mg twice daily group had an increase from baseline of at least one SBM per week, compared with 55% in the placebo group (p ≤ 0.001).
  • Individuals in the alvimopan treatment groups versus the placebo group reported moderate or substantial opioid-induced bowel dysfunction global improvement during the treatment period (p ≤ 0.003).
  • All alvimopan groups reported improvement in bowel  evacuation throughout the treatment period (p ≤ 0.009).
  • Reports of pain or total daily dose of opioid did not change significantly throughout the study.
  • All groups had stable scores on the Himmelsbach Withdrawal Scale.

Conclusions

Oral alvimopan increases the frequency of SBMs and improves symptoms in adults on opioid pain regimens.

Limitations

  • The study did not include patients with cancer; therefore, the results cannot be generalized to that population.
  • The amount of opioid taken by participants was only the equivalent of at least 30 mg of oral morphine daily.
  • After withdrawals, the treatment groups were below the calculated sample size of 125 to achieve 90% power. For patients who withdrew from the study and did not have complete data sets, the last recorded observations for each endpoint were carried forward.

Nursing Implications

Oral alvimopan may be effective for the treatment of opioid-induced constipation in patients taking opioids for chronic pain and may improve opioid-induced bowel dysfunction symptoms. Use of alvimopan does not appear to compromise analgesia or induce opioid abstinence. Additional study is necessary to look at efficacy with an oncology population and determine long-term efficacy, as well as an optimal dosing regimen.