August 21, 2019
By Reuters Staff
NEW YORK (Reuters Health) - The novel mu-opioid-receptor agonist NKTR-181 appears to provide long-term pain relief in patients with chronic low-back pain (CLBP), according to results from the uncontrolled, open-label SUMMIT-08 LTS study.
NKTR-181 is designed to have a reduced rate and extent of entry into the central nervous system, compared with other opioids, which should translate into less euphoria and abuse potential, researchers say.
Dr. Jeffrey Gudin of Rutgers New Jersey Medical School, in Newark, New Jersey, and colleagues tested the safety, tolerability and, as a secondary outcome, effectiveness of six different doses of NKTR-181 (ranging from 100 mg to 600 mg twice daily) in a 52-week study of 638 patients with CLBP (93%) or other chronic noncancer pain conditions.
Overall, 37% of participants discontinued early: 73 withdrew, 67 had adverse events, 32 were lost to follow-up, 27 had protocol deviations, and 21 withdrew for other reasons.
About half of the patients (47%) had one or more drug-related treatment-emergent adverse events (TEAEs), most commonly constipation (24%) and nausea (9%), the researchers report in Pain Medicine, online July 30.
Ten percent of patients discontinued treatment due to TEAEs, and none of the serious TEAEs (reported in 5% of patients) were deemed related to NKTR-181.
Upon discontinuation of NKTR-181, nine of 487 patients experienced mild opioid withdrawal and one had moderate opioid-withdrawal symptoms.
The mean pain intensity decreased from 4.6/10 at baseline to 2.7/10 at the end of the titration period. Reduced pain intensity was maintained for the duration of treatment once a stable dose of KNTR-181 was reached.
"Overall, NKTR-181 has a favorable safety profile with long-term use, and the results of this study, along with the results from the SUMMIT-07 study, support the conclusion that NKTR-181 is a safe and effective option for patients with CLBP," the researchers conclude.
In SUMMIT-07, the mean pain score during the randomized portion of the trial (when patients were allocated blindly to continued NKTR-181 versus switching to placebo) increased by 0.92/10 with continued NKTR-181 versus 1.46/10 with placebo (P=0.002).
There are no published studies comparing NKTR-181 with other opioid or nonopioid analgesics. According to the website of its manufacturer, Nektar Therapeutics, the U.S. Food and Drug Administration has granted NKTR-181 Fast Track designation for the treatment of moderate to severe chronic pain.
Nektar Therapeutics funded the study and employed several of the authors.
Dr. Gudin did not respond to a request for comments.
Pain Med 2019.
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