The development of safe and effective medications for the treatment of alcohol use disorders (AUDs) is a public health priority. Stress and mood are significant components of relapse in addiction, including alcohol dependence. The kappa opioid receptor (KOR) system plays a role in relapse to substance use and KOR antagonism has the potential to play an important role in the treatment of mood and substance use disorders. CERC-501 is an oral, once daily, highly specific and bioavailable KOR antagonist that reduces the EtOH preference behaviors of P-preferring rats, alleviates nicotine withdrawal syndrome in mice, and reduces depression- and anxiety- behaviors in animal models. CERC-501 was well tolerated in the three completed Phase 1 human studies (SAD, MAD and PET study). The primary objectives of the proposal are to enable pre-IND activities, file an IND for a new formulation and complete a pharmacokinetic and safety study of the new formulation. The pre-IND activities include development of new enteric coated formulation (CERC-501 EC) designed for maximal dispersion and release in the small intestine, bypassing the stomach. Cerecor will conduct a repeat-dose range-finding study, 6-month safety study with CERC-501 EC in minipigs and file an IND with FDA's DAAAP for the treatment of AUDs. Cerecor will conduct a pharmacokinetic (PK) study in healthy humans that will assess the bioavailability and PK profile of the CERC-501 EC, compare systemic exposure of CERC-501 EC to the current formulation and assess if food impacts bioavailability. Lastly, Cerecor will conduct a 9-month toxicology study with CERC-501 in dogs, so as to conclude the toxicology program that is required to support administration longer than 6 months in patients. Cerecor plans to register CERC-501 EC as new pharmacotherapy for AUDs. CERC-501 EC will be indicated for the maintenance of abstinence from alcohol and reduction in heavy drinking days in patients who are abstinent at treatment initiation and ii) for the reduction of heavy drinking in patients who are actively drinking at treatment initiation. After initial registration for treatment of AUD is completed clinical studies in co-occurring disorders, AUD and depression will be conducted.

Public Health Relevance

The development of safe and effective medications for the treatment of alcohol use disorders (AUDs) is a public health priority. The kappa opioid receptor (KOR) system plays a role in relapse to substance use and CERC-501, a KOR antagonist, has the potential to play an important role in the treatment of AUDs. We propose to conduct pre-IND activities, file an IND for a new formulation, complete a PK study of the new formulation and ultimately register and commercialize CERC-501 EC as a new pharmacotherapy for AUDs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II (U44)
Project #
1U44AA025253-01
Application #
9192119
Study Section
Special Emphasis Panel (ZAA1-DD (06))
Program Officer
Fertig, Joanne
Project Start
2016-07-20
Project End
2017-06-30
Budget Start
2016-07-20
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$1,000,000
Indirect Cost
Name
Cerecor. Inc.
Department
Type
DUNS #
968799028
City
Baltimore
State
MD
Country
United States
Zip Code
21202