Nektar reports promising results from Phase I study of constipation drug

NKTR-118 was also shown to be safe and generally well-tolerated at doses up to 250mg twice daily, with no serious or severe adverse events. The pharmacokinetics of NKTR-118 were dose-proportional and the observed terminal half-life of the drug was approximately eleven hours, independent of dose. This compares to a known half-life of between 45 and 100 minutes for naloxone.

At all dose levels, NKTR-118 was rapidly absorbed after oral administration, as evidenced by a steep increase of plasma NKTR-118 concentration. Plasma concentrations of NKTR-118-glucuronide were approximately 100-fold less than plasma NKTR-118 concentrations. The primary objective of this Phase Imulti-dose, double-blind, randomized, placebo-controlled study was to evaluate the safety and tolerability of multiple doses of oral NKTR-118 in healthy human subjects not receiving opioid therapy. A total of 32 subjects enrolled in the trial.

NKTR-118 is Nektar’s proprietary peripheral opioid antagonist candidate currently in a Phase II trial in patients with opioid-induced bowel dysfunction, including opioid-induced constipation.

Timothy Riley, vice president of PEGylation Research at Nektar, said: “For the first time, it has now been shown that Nektar’s proprietary PEGylation technology can be used to enhance oral bioavailability for a small molecule drug. In addition, this PEGylated drug exhibited an exceptionally long half-life of eleven hours, enabling a once-daily dosing regimen for NKTR-118 as an oral therapy.”