Safety, tolerability, and pharmacokinetics of multiple ascending doses of naloxegol.

Opioid-induced constipation (OIC) is the most common and often a treatment-limiting adverse event (AE) of opioid therapy for chronic pain. Naloxegol (previously NKTR-118), a PEGylated derivative of naloxone that has minimal penetration of the central nervous system, has received regulatory approval as an oral therapy for OIC. This randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study was performed to assess safety, tolerability, and pharmacokinetics of multiple doses of naloxegol in healthy volunteers.

Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending-dose study.

This randomized, double-blind, placebo-controlled, ascending-dose, crossover study evaluated single oral doses of naloxegol (NKTR-118; 8, 15, 30, 60, 125, 250, 500, and 1000 mg), a PEGylated derivative of naloxone, for safety and tolerability, antagonism of peripheral and central nervous system (CNS) effects of intravenous morphine, and pharmacokinetics. Healthy men were randomized 1:1 to naloxegol or naloxegol-matching placebo administered with morphine and lactulose in a 2-period crossover design. Periods were separated by a 5- to 7-day washout.

A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors.

Purpose: This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol.

Experimental Design: Patients with refractory solid malignancies were enrolled and assigned to escalating-dose cohorts. Patients received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w × 3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary end point using a standard 3 + 3 design.

Randomized, double-blind, placebo-controlled study of the abuse potential of different formulations of oral oxycodone.

Objective: The objective of this study was to evaluate the pharmacokinetics and abuse potential of different formulations of oxycodone.

Design: The participants completed an 8-day, placebo-controlled trial with four phases: naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation.

Subjects: Nineteen healthy, male, recreational drug abusers participated in this study.