Phase III Study: Naloxegol Improves Opioid-Induced Constipation
Drug compared with placebo in 3-month trial (Nov. 12)Positive top-line results have been reported from two phase III trials and one safety extension trial in patients with non–cancer-related pain and opioid-induced constipation (OIC). These studies evaluated the safety and efficacy of naloxegol (AstraZeneca) –– an oral, peripherally acting mu-opioid receptor antagonist for the treatment of OIC, a common side effect of prescription opioids.
KODIAC-04 and KODIAC-05 are multicenter, randomized, double-blind, placebo-controlled pivotal trials of 12 weeks duration evaluating naloxegol 12.5 mg and 25 mg administered once daily. The primary endpoint in both trials was the percentage of OIC responders versus placebo over 12 weeks of treatment. A responder was defined as having at least three spontaneous bowel movements (SBMs) per week, with an increase of at least one SBM per week over baseline, for at least 9 out of 12 weeks, and at least 3 out of the last 4 weeks.
In the KODIAC-04 trial, both naloxegol doses (12.5 mg and 25 mg) demonstrated statistically significant results for the primary endpoint. The P values were 0.015 and 0.001, respectively.
- In the KODIAC-05 trial, the 25-mg dose demonstrated a statistically significant result for the primary endpoint, but the 12.5-mg dose did not. The P values were 0.202 for 12.5 mg and 0.021 for 25 mg.
- The analyses also showed no clinically relevant imbalances in serious adverse events (SAEs) — including externally adjudicated major cardiovascular events — across the three treatment arms in KODIAC-04, -05, and -07 (the safety extension of KODIAC-04). The most common AEs in the naloxegol treatment arms were abdominal pain, diarrhea, and nausea. In KODIAC-07, the occurrence of AEs and SAEs was lower than in KODIAC-04 and -05. Among nonserious adverse events, arthralgia was the most common and was reported only in patients in the naloxegol 25-mg arm. All other common AEs were distributed similarly across the three treatment arms. In KODIAC-04 and -05, for either naloxegol dose compared with placebo, there were no significant differences in the change from baseline in the mean daily pain scores or in the mean total daily opioid dose.
Source: AstraZeneca; November 12, 2012.