Oral NKTR-118 Scientific and Clinical Data Presentations
Oral NKTR-118 is an oral drug that combines Nektar's advanced small molecule PEGylation technology platform with naloxol, a derivative of the opioid-antagonist drug, naloxone. The drug is under development for the treatment of opioid bowel dysfunction (OBD), including opioid-induced constipation (OIC).
The antagonist Oral NKTR-118 targets mu-opioid receptors within the enteric nervous system, which mediate OBD, a symptom complex resulting from opioid use that encompasses constipation, bloating, abdominal cramping, and gastroesophageal reflux. Constipation is the hallmark of this syndrome, and is generally its most prominent component. Oral NKTR-118 is currently in a second Phase 1 trial to evaluate the safety and tolerability of repeated dose administration.
According to IMS Health, more than 200 million prescriptions were written for opioids in 2006 in the United States, alone. Many studies indicate that a high percentage of patients receiving opioids are likely to experience significant constipation and other symptoms of OBD. Currently, there are no specific drugs approved that are indicated to treat OIC. Stool softeners or laxatives may be ineffective for many patients with OIC and they are often associated with side effects like diarrhea and stomach cramps.
In preclinical studies, Nektar's PEGylation technology has been shown to prevent oral NKTR-118 from crossing the blood-brain barrier, an important potential advance for this and possibly many other small molecule therapies.
In a single-dose Phase 1 trial, Oral NKTR-118 was shown to reverse the effects of morphine on gastrointestinal transit time at doses that do not reverse a central opiate effect as measured by pupillometry, demonstrating the potential of the drug to relieve constipation while not reversing central analgesic effects.
- Poster: 20th AAPM Annual Clinical Meeting — October 10, 2009 — "NKTR-118 Significantly Reverses Opioid-Induced Constipation"
- Poster #140: ACCP 38th Annual Meeting — September 13, 2008 — "Comparative Bioavailability of NKTR-118 Tablets and Solution: A Case of Bioequivalence Between Dosage Forms for a Rapidly Absorbed Drug"
- Poster #141: ACCP 38th Annual Meeting — September 13, 2008 — "NKTR-118, An Oral Peripheral Opioid Antagonist, Has Low Potential for Drug-Drug Interactions"
- Press Release: Nektar Announces Positive Results from Phase 2 Study of Oral NKTR-118 in Patients with Opioid-Induced Constipation (OIC); Highly Statistically Significant Results Achieved at Two Dose Levels with No Reversal of Analgesia — March 2, 2009
- Press Release: Oral NKTR-118 Shows Substantial Oral Bioavailability and Extended Half-Life In Phase 1 Clinical Data Presented at American Pain Society Meeting — May 7, 2008
- Poster #210: Results from a Phase 1, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose Study Evaluating the Safety, Tolerability and Pharmacokinetics of Oral Doses of Oral NKTR-118 (PEG-Naloxol) — May 7, 2008
- Press Release: Positive Results for Oral NKTR-118 (oral PEG-naloxol) Presented At American Academy of Pain Management Meeting — September 26, 2007
- Poster #27: Clinical Investigation of Oral NKTR-118 as a Selective Oral Peripheral Opioid Antagonist Presented at the American Academy of Pain Management Meeting in Las Vegas, Nevada — September 28, 2007
- Poster #28: Oral NKTR-118 (oral PEG-naloxol), a PEGylated Derivative of Naloxone; Demonstration of Selective Peripheral Opioid Antagonism After Oral Administration in Preclinical Models Presented at the American Academy of Pain Management Meeting in Las Vegas, Nevada — September 28, 2007
- Press Release: Nektar Presents Positive Results from Phase 1 Clinical Trial of Oral NKTR-118 (oral PEG-naloxol) at American College of Clinical Pharmacology Meeting — September 10, 2007
- Poster #36: Evaluation of PEG-naloxol (Oral NKTR-118) as an Oral Peripheral Opioid Antagonist in Healthy Male Subjects: A Double-Blind, Placebo-Controlled, Dose Escalation Crossover Study - Presented at the American College of Clinical Pharmacology 36th Annual Meeting in San Francisco, CA — September 10, 2007 — Poster Session II
