Status:
COMPLETED
The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers
Lead Sponsor:
National Institutes of Health Clinical Center (CC)
Collaborating Sponsors:
National Institute of Allergy and Infectious Diseases (NIAID)
Conditions:
Opiod Use Disorder
Eligibility:
All Genders
18-65 years
Phase:
PHASE1
Brief Summary
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 ca...
Detailed Description
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...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Must have the ability to understand and must personally sign a written informed consent form, which must be obtained prior to initiation of study procedures.
- Must be between 18 and 65 years of age, inclusive.
- Must have discontinued use of nicotine and nicotine containing products including vaping or juuling from 90 days prior to study drug dosing and throughout the study duration.
- Must be willing to abstain from any food or beverages containing alcohol 72 hours prior to first dose and through follow-up visit.
- Must be willing to abstain from cannabis 72 hours prior to first dose and through follow-up visit.
- Must be willing to abstain from caffeine (including tea, coffee, chocolate) or grapefruit, Seville orange juice or other methyl xanthine containing foods (e.g. theophylline, theobromine, tea leaves, yerba mate, kola nuts and guarana berries) 72 hours prior to the first dose and through follow- up visit.
- Must have a body mass index (BMI) from 19 to 30 kg/m\^2 (inclusive) at screening.
- Must be human immunodeficiency virus type 1 (HIV-1) antibody negative at screening.
- Must be hepatitis B (HBV) surface antigen negative at screening.
- Must be hepatitis C (HCV) antibody or RNA negative at screening.
- Male subjects must refrain from sperm donation from clinic admission, throughout the study period, and continuing for at least 90 days following the last dose of study drug.
- Subjects must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.
- Must be willing to comply with contraception guidelines below Contraception:
- The fetal risks associated with ANS-6637 are not known, but pre- clinical animal data demonstrate some risk. Subjects must agree not to become pregnant or impregnate a female. Females of childbearing potential must have a reproductive risk assessment done to determine the risk of undetectable pregnancy at study start \[i.e. sexual and contraceptive history for 30 days preceding screening\] pregnancy test at screening and baseline (Day 0). For the duration of the study, subject and their partners must practice two non-hormonal methods of birth control, having begun no less than 30 days, without interruption, prior to screening. They must continue to use both methods until 3 months after stopping the study drug. Two of the three methods of birth control listed below MUST be used, or an alternative combination offering very high efficacy, per the PI, in consultation with the Sponsor Medical Monitor may be considered:
- Male or female condoms \[but not both\] with a spermicide
- Diaphragm with a spermicide
- Intrauterine device (IUD)
- If pregnancy is suspected or should occur, subjects must notify the study staff immediately.
- Must, in the opinion of the Investigator, be in good health based upon medical history and physical examination, and screening laboratory evaluations.
- Judged to be healthy based on medical history, physical examination, vital signs, and clinical laboratory tests at screening and Day 0: liver function tests (AST, ALT, Tbili) less than or equal to upper limit of normal \[ULN\], platelets (PLT) \>150,000/ microliter, hemoglobin (Hgb) \>13 g/dL (males); \>12 g/dL (females), CK less than or equal to 2x ULN, Amylase/lipase \< ULN, thyroid function tests \[TSH and T4\] within normal range, fasting total cholesterol \<240 mg/dL, or fasting triglycerides \<240 mg/dL, per DAIDS AE table and Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Trials AE table for total bilirubin \[Tbili\] only.
- Must be willing and able to comply with all study requirements.
- EXCLUSION CRITERIA:
- Therapy with any prescription, over-the-counter (OTC), herbal, or holistic medications, including hormonal contraceptives by any route, within 5 half- lives of the agent prior to receipt of any study medications will not be permitted with the following exception: Intermittent or short-course therapy (\<14 days) with prescription or OTC medications, herbals, or holistic medications within the screening period prior to starting study drugs may be permitted after review by the investigators on a case-by-case basis for potential drug interactions. Receipt of influenza vaccination will be allowed prior to, during, and/or after the study.
- Have any serious or active medical, surgical, or psychiatric conditions which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
- Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to screening.
- Have current, or a history of mild to severe alcohol use, cannabis or other substance use disorder including any use of illicit drugs as defined by DSM-5 criteria, within 12 months of first study dose
- Renal impairment (chronic renal insufficiency of any chronic kidney disease stage, or acute renal failure not induced by drug therapy defined as eGFR \<90 ml/min)
- Have a positive urine drug test (ethanol, cannabis, barbiturates, cocaine, opiates, or amphetamines) at Screening or Day 0.
- History of flushing or intolerance related to alcohol consumption using the NIAAA screening assessment questionnaire tool for alcohol flushing
- Inability to obtain venous access for sample collection.
- Have a history of significant drug sensitivity or drug allergy to any benzodiazepines.
- Known hypersensitivity to formulation excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.
- Have been treated with systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies).
- Presence or history of clinically significant cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities.
- Have clinically significant ECG abnormalities or any of the following ECG abnormalities at Screening: PR \>220 msec; QRS \>120 msec; QTcF \>450 msec; HR \<40 beats per minute; second or third degree heart block.
- Have a history or family history of Long QT Syndrome, Brugada syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years.
- Have history of syncope, palpitations, unexplained dizziness or chronic nausea or headaches.
- Have an implanted defibrillator or pacemaker.
- Have a history of liver disease, including Gilbert's Disease.
- Any clinically significant electrolyte abnormality (outside of NIH normal reference ranges) at screening (e.g., hypokalemia, hypocalcemia, hypomagnesemia) or any condition that could lead to abnormal electrolyte disturbances (eg, eating disorder).
- Have a history of taking dopamine antagonists/anti-psychotics.
- Are unable to comply with study requirements.
- Positive urine toxicology screen
Exclusion
Key Trial Info
Start Date :
March 1 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 30 2019
Estimated Enrollment :
26 Patients enrolled
Trial Details
Trial ID
NCT03831971
Start Date
March 1 2019
End Date
December 30 2019
Last Update
August 3 2020
Active Locations (1)
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1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892