Oral Nalbuphine®ER Performs Well in Phase 2 Trial of Prurigo Nodularis

Trevi Therapeutics, Inc.’s Oral Nalbuphine^®ER reduced itch intensity and improved quality of life in prurigo nodularis patients, according to a Phase 2 Trial.

Nalbuphine ER is an oral extended release mu receptor antagonist and kappa receptor agonist. Both modalities have been shown to be effective in treating itch. The Company is pursuing two conditions for clinical development: uremic pruritus and prurigo nodularis. Trevi is preparing for an end of Phase 2 meeting for prurigo nodularis, has already held an end of Phase 2 meeting with FDA for uremic pruritus, and will initiate Phase 3 trials in both conditions in 2017.

The Phase 2 three-arm study evaluated the safety and anti-pruritic efficacy of Nalbuphine ER tablets dosed twice-daily at 90mg and 180mg in 62 patients in the United States and Europe. Patients with moderate-to-severe itch intensity, defined as ≥ 5 on the 0-10 Numerical Rating Score (NRS) scale, were enrolled to evaluate drug efficacy across a representative patient population for treatment of this chronic indication. The actual average baseline worst itch for enrolled patients was ≥ 8, indicating the severe nature of the disease.

The study consisted of a titration period of two weeks, followed by an eight-week blinded period on a fixed dose of drug or placebo, and a two-week wash-out period. At the end of the wash-out period, patients were eligible to roll over into a one-year open label extension study. The Company expects the open label extension study to be completed in the third quarter of 2017.

The main outcome variables for this study were responder analyses of the proportion of patients with at least a 30% or 50% reduction in their 7-day worst-itch intensity NRS from baseline to completion of treatment at week 10 or last observation visit. The proportion of patients in the Nalbuphine ER 180 mg BID arm meeting 50% responder criteria at week 10 or last observed visit (MITT population with n=18) approached statistical significance (p=0.083), and this arm met statistical significance for patients (n=12) completing treatment (p=0.028). The mean change in worst itch NRS was additionally evaluated, and the MITT population of the Nalbuphine ER 180 mg BID arm as compared to placebo approached statistical significance (p=0.083) as well. This arm also met statistical significance for patients (n=12) completing treatment (p=0.025). 

The ItchyQoL™ secondary endpoint, 22 questions that measure how pruritus affects a patient’s quality of life, provided supportive evidence of a favorable treatment effect on reduction in itch intensity compared to placebo. Change from baseline in the ItchyQoL total score was significantly more favorable for the Nalbuphine ER 180 mg BID dose compared to placebo (p=0.022), the study showed.

The most common adverse events in the study were dizziness, nausea, headaches, and fatigue, the majority of which were grade 1 or 2. As seen previously, the incidence rate of these events was similar to placebo after the titration period. No serious adverse events attributed to the drug were observed, and the study Data and Safety Monitoring Board raised no issues that affected the continuation of the study or required modification of study procedures.