Many patients with advanced cancer require opioids to treat pain. In some patients, this leads to opioid-induced constipation. In a plenary session at the recent American College of Gastroenterology in San Diego, researchers presented data from a phase II study of the novel oral drug NKTR-118 (PEG-naloxol) that showed it increased the frequency of spontaneous bowel movements (SBMs) without negatively affecting the opioids’ analgesic effects.
Many patients with advanced cancer require opioids to treat pain. In some patients, this leads to opioid-induced constipation (OIC). In a plenary session at the recent American College of Gastroenterology in San Diego, researchers presented data from a phase II study of the novel oral drug NKTR-118 (PEG-naloxol) that showed it increased the frequency of spontaneous bowel movements (SBMs) without negatively affecting the opioids’ analgesic effects.
The double-blind, placebo-controlled study included 208 patients with OIC, defined as <3 SBMs per week. Patients were randomized to receive either 25 mg or 50 mg of NKTR-118 or placebo once daily. Compared with baseline measures, patients in the treatment arms experienced a significant increase in SBMs during the first week of treatment than patients in either placebo group. Those who received the lower dose of NKTR-118 had a change in baseline of 3.6 SBMs compared with 1.9 for those in the placebo group (P = .002). The increase in SBMs from baseline was nearly double in the 50-mg arm compared with 1.9 in the placebo group, at 4.4 (P = .0001). Over a 4-week course of treatment, the higher rate of SBMs compared to baseline persisted for both treatment arms.
Compared to placebo, the median time to first SBM was significantly shorter in both treatment arms. In the 25-mg dose cohort, the first SBM was 6.6 hours after initiating treatment compared with 48.6 hours for those receiving placebo (P = .001); for patients in the 50-mg dose cohort, median time to first SBM was 2.9 hours compared with 44.9 hours in the corresponding placebo group (P <.002).
Lynn Webster, MD, medical director of Lifetree Clinical Research in Utah, was the lead investigator for the trial, and he said, “Patients who take opioids are at risk of experiencing the painful and potentially serious side effect of OIC—which can require patients to seek remedies only available in a hospital or in-office setting.” According to Dr Webster, the results of the trial indicated that approval of NKTR-118 would offer patients with OIC “a simple and noninvasive oral treatment that may improve their gastrointestinal function.”
To determine whether NKTR-118 countered any of the opioid-mediated analgesia, researchers used the Numeric Rating Scale pain scores. They found no increase in mean daily opiate use, suggesting that the drug did not reverse the effectiveness of the opioids.
Patients were most likely to experience gastrointestinal-related effects from NKTR-118, which appeared to be dose dependent. Diarrhea was reported by 31% of patients in the 50-mg arm compared with 13% in the 25-mg arm. The incidences of diarrhea were 4% and 5% in the placebo arms. Abdominal pain was also notably higher in the treatment arms, at 30% for the 25-mg group and 17% for the 50-mg group; compared with 7% and 0% for the placebo arms. Only one serious adverse effect was reported, which was in the 50-mg cohort, where a patient was hospitalized for abdominal cramping. Abstract 26.
Webster L, Blonsky ER, Matz P, et al. Efficacy, safety and pharmacokinetics of oral NKTR-118 in patients with opioid-induced constipation: Results of a randomized, double-blind, placebo-controlled phase 2 study. Presented at: American College of Gastroenterology Scientific Meeting and Postgraduate Course; October 23-28, 2009; San Diego, CA.