LAS VEGAS — NKTR-181, an oral full mu-opioid receptor agonist administered twice daily, was shown to reduce pain with good tolerability and few withdrawal symptoms in patients with moderate to severe chronic low back pain, according to research presented at PAINWeek 2017, September 5-9, in Las Vegas, Nevada.1
In the phase 3 randomized withdrawal study (SUMMIT-07), researchers compared NKTR-181 (n=309) with placebo (n=301) in opioid-naive adults with moderate to severe chronic low back pain uncontrolled with non-opioid analgesics.
The 12-week placebo-controlled trial was preceded by an open-label titration period. The primary end point for efficacy was mean change in weekly pain score from baseline at 12 weeks.
Researchers also investigated the frequency of reported adverse events and withdrawal symptoms using the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale following the open-label phase and during a 1-week taper period or following early discontinuation.1,2
After 12 weeks of treatment, the change in weekly pain score was greater for NKTR-181 compared with placebo (least squares mean +0.92 vs +1.46; P =.002). Among the NKTR-181 group, significantly more patients had a ≥30% and ≥50% reduction in pain from baseline (71.2% and 51.5%, respectively) compared with the placebo group (57.1% and 37.9%; P <.001 and =.001).2
More patients receiving NKTR-181 considered themselves “improved” or “very much improved” on the Patient Global Impression of Change scale compared with those receiving placebo (51.5% vs 33.2%; P <.001). Similarly, significantly improved scores for sleep disturbance, sleep problems, and sleep adequacy on the Medical Outcomes Study Sleep Scale—Revised were seen in patients receiving NKRT-181 vs placebo.2
Following the open-label, dose-titration phase when patients either continued NKTR-181 or abruptly switched to placebo, Clinical Opioid Withdrawal Scale scores indicated mild withdrawal in 7 patients in the placebo group (2.4%) and 3 patients in the NKTR-181 group (1.0%) on day 8. On day 15, mild withdrawal was noted in 1 patient in the placebo group (0.4%) and 4 patients in the NKTR-181 group (1.4%).1
Following the 1-week taper period at the end of the 12-week randomized study, mild withdrawal was noted in 5 patients receiving NKTR-181 (2.3%) and 1 patient receiving placebo (0.5%).1
Adverse events were noted in 54.4% of patients receiving NKTR-181 compared with 49.8% of patients receiving placebo. Among patients receiving NKTR-181 vs placebo, the most common adverse events included nausea (10.4% vs 6.0%), constipation (8.7% vs 3.0%), and vomiting (4.9% vs 1.7%).2
The authors concluded: “Opioids that are associated with minimal withdrawal symptoms when discontinued may be of clinical utility in treating patients with chronic pain.”1
- Henningfield J, Markman J, Gudin J, et al. Measuring withdrawal in a phase 3 study of a new analgesic, NKTR-181, in subjects with moderate to severe chronic low-back pain. Presented at: PAINWeek 2017; September 5-9; Las Vegas, Nevada. Abstract 38.
- Markman J, Gudin J, Rauck R, et al. Efficacy, safety, and tolerability of NKTR-181 in patients with moderate to severe chronic low-back pain: a phase 3 study. Presented at: PAINWeek 2017; September 5-9; Las Vegas, Nevada. Abstract 41.