U01DA058541

PDE7 Inhibitor for the Treatment of Cocaine Use Disorder - Abstract

The goal of this project is to advance to the clinic an oral drug candidate to treat cocaine use disorder (CUD). An estimated 1.3 million persons in the US have CUD, and more than 19,000 people die each year from overdoses involving cocaine. There are no approved drug treatments for cocaine abuse.

Most individuals seeking treatment for CUD receive only psychosocial treatments that have high treatment dropout and relapse rates. Omeros developed a novel class of small molecules that selectively inhibit phosphodiesterase 7 (PDE7). Cocaine inhibits the reuptake of dopamine and other monoamine neurotransmitters, eliciting dopamine surges that are considered the primary mechanism through which cocaine evokes reward and initiates addiction.

The PDE7 class of inhibitors is thought to restore the physiological dopamine phasic-to-tonic ratio that is altered by chronic exposure to drugs of abuse to reduce craving. The Omeros PDE7 inhibitor, OMS182399, is orally available with pharmacokinetics that support once-daily dosing. OMS182399 reduces cocaine seeking in preclinical animal models of CUD and is safe and tolerable in healthy volunteers.

The objective of this U01 project is to advance OMS182399 toward clinical trials for CUD by completing required preclinical interaction/toxicology studies and then performing a clinical study to test the safety, tolerability, PK, and preliminary efficacy of OMS182399 in persons with CUD. This project meets the goals of PAR-19-327 in that it accelerates the development of a novel oral drug candidate to treat CUD, for which there are no approved drugs.

Aim 1 is to conduct IND-enabling interaction/toxicology studies of OMS182399 in rats and non-human primates. Although prior studies showed that OMS182399 is safe in rats, cynomolgus monkeys, and people, the FDA requires drug interaction safety studies to ensure that it is safe in people with CUD who may use cocaine while in treatment.

Aim 2 is to prepare and submit an IND application for the clinical trial proposed in Aim 3. Omeros will write and submit an Investigational New Drug (IND) application with the FDA to test OMS182399 for safety, tolerability, PK, and preliminary efficacy during concurrent cocaine administration in persons with CUD.

Aim 3 is to conduct a 2-week randomized, single dose, double-blind, parallel group, in-patient clinical study to compare the safety, tolerability, PK, and preliminary efficacy of oral OMS182399 to placebo (vehicle solution) in the treatment of adults with CUD who receive concurrent intravenous cocaine. Outcomes will be tolerability, safety, subjective preliminary efficacy measures, and pharmacokinetics.

Successful completion of this project will lead to a future Phase II clinical proof-of-concept study to advance OMS182399 toward FDA approval for CUD, which will have vast public health implications.

Omeros Corporation

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]

Seattle, Washington 981194240 United States

Single Zip Code

Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional) (PAR-19-327)

Amendment Since initial award the total obligations have increased 384% from $1,382,131 to $6,689,019.