UH3DA047720

Evaluation of Safety and Pharmacokinetics of Naltrexone Implant

New medication treatment approaches are needed to help address the severe epidemic of opioid use disorder (OUD) and opioid overdose deaths in the US. Currently available medications, methadone, buprenorphine, and extended-release injection naltrexone (XR-NTX; trade name: Vivitrol), are highly efficacious, but their effectiveness in practice is limited by poor adherence, with many patients stopping treatment prematurely and relapsing.

The goal of this proposal is to develop an innovative long-acting subcutaneous implanted formulation of naltrexone, the O'Neil Long-Acting Naltrexone Implant (OLANI), towards FDA approval. Expected to produce naltrexone blood levels sufficient to block the effects of opioids for 6 months after implant, OLANI circumvents the need for adherence to monthly injections with XR-NTX and could represent an important new addition to the medical armamentarium for the treatment of OUD.

The OLANI has been in development by an Australian company, Go Medical, for 20 years with several prototypes evaluated in controlled clinical trials and used clinically in Australia. The current formulation has higher drug loading and a better release profile and is manufactured in a GMP facility. It has been used clinically in over 800 patients, giving confidence that the product can be successfully developed in the US.

Go Medical and the current team of investigators met with the FDA to chart a development path towards a new drug application (NDA) via the 505(b)(2) pathway with Vivitrol as a comparator product. An application for an IND (# 134996) is under review by the FDA. This proposal seeks NIDA's support under the UG3/UH3 mechanism to conduct the studies recommended by the FDA for the 505(b)(2) pathway to approval.

Under the UG3 phase, Study 1 will evaluate local tissue toxicity of OLANI in a minipig model, and Study 2 will generate pilot pharmacokinetic (PK) data of OLANI in healthy subjects in order to determine power and finalize sample size for a subsequent bioequivalence (BE) study and to support feasibility and tolerability. If there are no safety concerns and naltrexone blood levels are adequate in the UG3 phase, then in the UH3 phase (Study 3) will be finalized in consultation with NIDA and FDA.

Study 3 will compare 6-month PK of OLANI versus XR-NTX as the reference drug to establish bioequivalence (BE) in terms of naltrexone blood levels, safety, and comparative effectiveness in patients with OUD. Patients will be randomized to receive either a single subcutaneous implantation of 3.6g dose of OLANI or repeat doses of Vivitrol 380 mg IM Q4 weeks for 24 weeks. Participants randomized to OLANI will be offered an additional implant at month 6.

We hypothesize that OLANI will have a systemic exposure (Cmax, Cmin, AUC0-180) and MEC of naltrexone blood levels comparable to XR-NTX. If OLANI is shown to provide a safe, feasible, and effective method of delivery of naltrexone at therapeutic levels for at least 6 months, it would represent a major advance in the field of OUD treatment, providing effective long-term relapse-prevention treatment to individuals with OUD.

Research Foundation For Mental Hygiene

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

New York United States

State-Wide

Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trials Optional) (RFA-DA-19-002)

Amendment Since initial award the End Date has been extended from 02/29/24 to 02/28/26 and the total obligations have increased 210% from $4,109,018 to $12,750,800.