Nalbuphine® ER is an oral extended release opioid with a unique opioid receptor dual µ-antagonist/κ-agonist mechanism of action. Based on the "opioid hypothesis" in itch, a drug with µ-opioid receptor antagonist or k-opioid receptor agonist properties would be expected to have anti-pruritic effects. Nalbuphine® ER has both mechanisms of action.
In a standard mouse model of itching, nalbuphine significantly attenuated scratching behavior induced by substance P, a well known pruritogen. In addition, nalbuphine has been effective in treating morphine-induced pruritus in multiple well-controlled, double-blinded clinical studies (Kjellberg 2001). Trevi completed a Phase 1 clinical study with Nalbuphine® ER in hemodialysis subjects with uremic pruritus and achieved a dose-dependent decrease in itch in the majority of the patients. More recently, Trevi completed a Phase 2/3 trial in uremic pruritus, an itch related to renal impairment, and a Phase 2 trial in prurigo nodularis, a dermatological itch condition. Both trials showed proof of concept data for robust reduction in itch and related secondary endpoints, despite being in unrelated itch conditions with differing patient populations. We believe this data lays the foundation for Nalbuphine® ER as the first and best potential treatment for severe, chronic itch.
Nalbuphine is a marketed drug currently available only as nalbuphine hydrochloride (HCl) for injection, a generic equivalent to Nubain®. It is approved in the United States for use in the relief of moderate to severe pain and as an analgesic. Nalbuphine is not a controlled drug in the United States or Europe. An oral dosage form of the drug is not commercially available.
|Phase 2/3 in Uremic Pruritus: Decrease in Itch||Phase 2 in Prurigo Nodularis: Responder Proportion with >50% Reduction in Itch|
Recent Posters and Publications on Nalbuphine® ER in Pruritus:
- Nalbuphine® ER Tablets in Hemodialysis Patients with Severe Uremic Pruritus: Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial, as presentd at National Kidney Foundation Spring 2016 Meeting.
- Long-Term Effects of Nalbuphine® ER Tablets in Hemodialysis Patients with Uremic Pruritus: A Multicenter Open-Label Trial, as presented at National Kidney Foundation Spring 2016 Meeting.
- A Multicenter, Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine® ER Tablets for the Treatment of Uremic Pruritus: Baseline Population Characteristics, as presented at the American Society of Nephrology’s Kidney Week 2015.
- Nalbuphine attenuates itch in the substance P-induced mouse model, as presented at 7th World Congress on Itch on September 21-23.
- A proof-of-concept study with pharmacokinetics demonstrating anti-pruritic activity of oral nalbuphine in hemodialysis patients with uremic pruritus, as presented at 2014 Annual Meeting of the Society for Investigative Dermatology.
- Pharmacokinetics of Nalbuphine Hydrochloride Extended Release Tablets in Hemodialysis and Healthy Subjects following Multiple Escalating Oral Doses, as presented at the 2014 meeting of the American College of Pharmacology.
- Exploring Clinical and Pharmacological Effects of Nalbuphine HCl Oral Tablets in Hemodialysis Subjects with Pruritus, as presented at American Society of Nephrology’s Kidney Week 2014.