Trevi Therapeutics' Oral Nalbuphine Demonstrates Reduced Abuse Potential in Clinical Study
核心洞察
Trevi Therapeutics' oral nalbuphine showed statistically significant lower "Drug Liking" compared to IV butorphanol in a human abuse potential (HAP) study.
The study assessed three doses of oral nalbuphine (81mg, 162mg, 486mg) against IV butorphanol and placebo in recreational drug users.
Secondary endpoints were consistent with the primary endpoint, with no serious adverse events reported during the study.
Trevi Therapeutics, Inc. (Nasdaq: TRVI) has announced positive topline results from a human abuse potential (HAP) study of its investigational therapy Haduvio™ (oral nalbuphine ER). The study evaluated the abuse potential of oral nalbuphine compared to intravenous (IV) butorphanol in recreational drug users.
The HAP study was a randomized, double-blind, double-dummy, active and placebo-controlled five-way crossover study. The primary endpoint was the peak effect (Emax) for "Drug Liking," assessed on a 100-point visual analog scale (VAS). Results showed statistically significant lower "Drug Liking" for the 81mg and 162mg doses of oral nalbuphine compared to 6mg IV butorphanol (p<0.0001 and p=0.0008, respectively). While the supratherapeutic dose of 486mg was numerically lower than butorphanol, the difference was not statistically significant (p=0.3221).
Key Findings
The study's primary endpoint, Mean Emax for "Drug Liking", showed the following results:
- Placebo: 51.8
- IV butorphanol (6mg): 82.3
- Oral nalbuphine (81mg): 71.2 (p<0.0001 vs butorphanol)
- Oral nalbuphine (162mg): 74.5 (p=0.0008 vs butorphanol)
- Oral nalbuphine (486mg): 81.1 (p=0.3221 vs butorphanol)
Secondary endpoints, including pharmacodynamic markers and patient-reported outcomes, were generally consistent with the primary endpoint. No serious adverse events were reported.
Expert Commentary
"We're very pleased with our study results," said James Cassella, Ph.D., Chief Development Officer of Trevi Therapeutics. "The positive butorphanol drug liking effect versus placebo demonstrates the validity and robustness of our study design... We look forward to reporting data from our two ongoing chronic cough studies in IPF (搜索) and RCC (搜索), two conditions where patients continue to have a significant unmet need."
Jack Henningfield, Ph.D., Vice President, Research, Health Policy and Abuse Liability at Pinney Associates, added, "This experience, coupled with these HAP results, continues to support the conclusion that nalbuphine extended-release has potential to address an important health need without the public safety risks posed by the opioids that are often prescribed for chronic cough."
Implications for Chronic Cough Treatment
Trevi Therapeutics is developing Haduvio™ (oral nalbuphine extended-release) for the treatment of chronic cough in patients with idiopathic pulmonary fibrosis (搜索) (IPF (搜索)) and refractory chronic cough (搜索) (RCC (搜索)). Nalbuphine acts as a kappa agonist and a mu antagonist (KAMA) on opioid receptors, which play a key role in controlling cough hypersensitivity. The company intends to submit the HAP study results as part of the 8-factor analysis of the abuse potential of nalbuphine ER in a new drug application (NDA).
Chronic cough affects a significant portion of IPF (搜索) patients, with up to 85% experiencing it. Refractory chronic cough (搜索) affects approximately 2-3 million adults in the U.S. There are currently no approved therapies for chronic cough in IPF or RCC (搜索) in the U.S., highlighting a significant unmet medical need.