NKTR-181 was found to be a safe, effective, and well tolerated treatment over the long term in patients with moderate to severe chronic low back pain (CLBP), according to results from a phase 3 trial published in Pain Medicine.
NKTR-181, a novel μ-opioid receptor agonist, has several advantages compared with conventional opioid drugs, including a slower entry into the central nervous system, delayed receptor binding, and long duration of effect. Previous studies have reported that NKTR-181 was associated with reduced incidence of central nervous system side effects and greater maintenance of pain reduction compared with placebo.
The goal of the current SUMMIT-08 study was to assess the safety and tolerability of NKTR-181 treatment for 52 weeks in patients with moderate to severe CLBP or chronic noncancer pain.
The uncontrolled multicenter open-label study had 3 phases: screening (21 days; visits 1 and 2), treatment (52 weeks; visits 3-22), and safety follow-up (~14 days after the last dose of study drug; visits 23 and 24). The study cohort included patients aged 18 to 75 years with a clinical diagnosis of moderate to severe CLBP or chronic noncancer pain.
Of 638 study participants, 431 had participated in the SUMMIT-07 study (214 patients treated with NKTR-181; 217 who received placebo), and 207 patients were enrolled de novo (n=134 opioid-experienced patients, n=73 opioid-naive patients). NKTR-181 was administered at doses of 100 to 600 mg twice daily. Safety assessments consisted in the evaluation of treatment-emergent adverse events (TEAEs) and of serious AEs. Opioid withdrawal was examined and clinical laboratory tests were conducted. NKTR-181 efficacy was assessed using the modified Brief Pain Inventory-Short Form.
During the study, 72% of patients reported ≥1 TEAEs, and 6% had a severe TEAE. The most common TEAEs were constipation (26%), which occurred particularly at higher doses of NKTR-181, and nausea (12%). Overall, NKTR-181 was well tolerated at doses ranging from 100 to 600 mg. TEAE related to NKTR-181 were documented in 17% of patients, and the most common were constipation (24%) and nausea (9%). Drug-related central nervous system TEAEs were reported in less than 5% of patients.
The most common events leading to treatment discontinuation were constipation (2%) and headache (1%). Serious TEAEs were reported in 5% of patients but deemed by the investigators to be unrelated to the study medication. AEs and patient wishes were the most common reasons for removal from the study (11% each), and 2% of patients elected to discontinue treatment because of lack of efficacy.
The mean pain intensity, assessed using modified Brief Pain Inventory-Short Form scores, decreased from 4.6±2.2 at baseline to 2.7±1.8 at the end of the dose titration period. Pain interference scores showed a similar pattern, with patients experiencing an improvement from baseline, which was maintained throughout the duration of the study. Once a stable dose was reached, most patients (79%) did not require further dose increases and maintained analgesia until the end of the 52-week treatment period.
Study limitations include the lack of a control group or active comparator arm and the exclusion of patients taking high doses of opioids, a population more likely to develop tolerance.
“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,” concluded the researchers.
Disclosure: This clinical trial was supported by Nektar Therapeutics, which developed NKTR-181. Please see the original reference for a full list of authors’ disclosures.
Gudin J, Rauck R, Argoff C, et al. Long-term safety and tolerability of NKTR-181 in patients with moderate to severe chronic low back pain or chronic noncancer pain: a phase 3 multicenter, open-label, 52-week study (SUMMIT-08 LTS) (published online July 30, 2019). Pain Med. doi:10.1093/pm/pnz169