Opiod Use Disorder Clinical Trial
Official title:
The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers (SEARCH PK)
Background:
Opioids are medicines that control pain. But they are often misused, which can lead to
illness and death. Opioids increase dopamine to the brain, which makes people feel good and
often causes them to crave drugs, leading to misuse and addiction. An investigational drug
ANS-6637 may lower the dopamine surge and stop opioid craving. Midazolam is a drug approved
for anxiety. Researchers want to give the two drugs together and see if ANS-6637 affects
midazolam levels, to help understand how ANS-6637 is used in the body.
Objective:
To study the safety, tolerability, and effects of ANS-6637 taken with and without midazolam.
Eligibility:
Healthy adults 18 65 years old
Design:
Participants will be screened with a medical history, physical exam, and blood and heart
tests. Participants who can get pregnant will have a pregnancy test.
Participants must agree to use 2 types of birth control during the study, if applicable.
Participants will stay at the clinic for 10 days. Meals will be provided. Participants will
not be allowed to:
Leave NIH campus
Eat or drink anything with caffeine, alcohol, or certain juices
Use any nicotine or related products (including vaping)
Use any medicines (including herbal)
During the clinic stay, participants will:
Fast overnight several times
Have blood drawn most days. Twice, a small tube will be inserted in an arm vein for frequent
blood samples.
Repeat screening tests and answer questions about their mood several times
Get midazolam syrup in water on 1 day
Take 6 ANS-6637 tablets by mouth on 5 days
Take both study drugs on 1 day
A few days later, participants will have a follow-up visit to repeat screening tests and
answer questions about their mood.
Opioid use causes a myriad of effects which contribute to significant morbidity and early
mortality, and is associated with risky sexual behavior and injection drug use (IDU), two
major forms of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission in
urban and suburban United States. Through these high-risk behaviors, persons with opioid use
disorder (OUD) develop both direct comorbidities (e.g. blood stream infections and infectious
endocarditis), as well as risk-associated illnesses (e.g. sexually transmitted infections,
HCV and hepatitis B virus [HBV]) which have considerable downstream health care effects. As
such, there is a need for pharmacologic agents in the treatment of OUD that go beyond
avoidance of withdrawal and facilitate decreased frequency or complete cessation of opioid
use.
The biologic mechanism of OUD, common to all forms of addiction, is a conditioned drug
cue-related response in the CNS, causing a dopamine surge. If effective, a central
pharmacologic strategy targeting the aberrant reward circuitry seen in OUD could potentially
reduce drug craving and result in opioid abstinence.
In the SEARCH Pharmacokinetic (PK) investigation, we aim to understand the pharmacokinetic
signal of the novel, oral agent ANS-6637, an aldehyde dehydrogenase 2 (ALDH-2) inhibitor that
has the potential to reduce dopamine surge in the CNS and inhibit opioid craving. In
preclinical studies, the active metabolite of ANS-6637, GS-548351, showed substrate dependent
inhibition of CYP3A in vitro, with little or no inhibitory effect on the activities of other
cytochrome P450 (CYP) enzymes. As such, the current investigation seeks to explore the
potential inhibition of CYP3A by ANS-6637 with the FDA-recommended CYP3A probe substrate,
midazolam.
;
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