Data from a phase II study demonstrated that oral NKTR-118 improved lower gastrointestinal dysfunction by increasing the frequency of bowel movements in patients with opioid-induced constipation, while simultaneously preserving opioid-mediated analgesia. NKTR-118, an oral peripherally-acting opioid antagonist, is an investigational product candidate in clinical development for the treatment of opioid-induced constipation.
In the phase II double blind, randomized, placebo-controlled study of 208 patients with opioid-induced constipation, NKTR-118 achieved the primary endpoint of change from baseline in spontaneous bowel movements (SBMs). Patients receiving either 25 mg or 50 mg of oral NKTR-118 once daily had a significantly greater change from baseline in SBMs during the first week of treatment than patients receiving placebo. The mean change from baseline in SBMs per week for patients receiving 25 mg NKTR-118 was 3.6 versus 1.9 in the placebo group>
The study also showed that there was a statistically significant difference in median time to first SBM for patients in the 25 mg and 50 mg dose cohorts as compared to placebo. Median time to first SBM for patients in the 25 mg dose cohort was 6.6 hours as compared to placebo which was 48.6 hours>
"Patients who take opioids are at risk of experiencing the painful and potentially serious side effect of opioid-induced constipation (OIC) -- which can require patients to seek remedies only available in a hospital or in-office setting," said Dr. Lynn Webster, Medical Director of Lifetree Clinical Research and lead clinical investigator of the phase II trial. "The results of the NKTR-118 phase II trial presented today indicate that, if approved, this product may have the potential to offer patients suffering from OIC a simple and non-invasive oral treatment that may improve their gastrointestinal function."
The study also showed there was no apparent reversal of opioid-mediated analgesia with any of the NKTR-118 dose groups, as measured by no change in Numeric Rating Scale (NRS) pain scores and no increase in mean daily opiate use.
The most commonly reported side effects from this Phase II study of NKTR-118 were dose dependent gastrointestinal-related effects. The majority of side effects for both the 5 and 25 mg dose cohorts were graded as mild by the investigators. Side effects included diarrhea (13% at 25 mg and 31% at 50 mg, versus 4% and 5% for the placebo arms), nausea (13% for 25 mg and 20% for 50 mg, versus 19% and 8% for the placebo arms) and abdominal pain (30% for 25 mg and 17% for 50 mg, versus 7% and 0% for the placebo arm). No treatment-related serious adverse events (SAE) for the 5 or 25 mg cohorts were observed. Only one patient experienced an SAE of hospitalization due to abdominal cramping in the 50 mg cohort.
These data from the Phase II clinical trial of NKTR-118 were presented today during the oral plenary session of the American College of Gastroenterology (ACG) 2009 Annual Clinical Meeting.