Opiod Use DisorderPhase 1NCT03831971
The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers
A Phase 1 study testing ANS-6637 in people with Opiod Use Disorder, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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 causes them to crave drugs, leading to misuse and addiction. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Opiod Use Disorder
- What is being tested?
- ANS-6637
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2019to 30 Dec 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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 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.
- Conditions
- Opiod Use Disorder
- Being tested
- ANS-6637
- Keywords
- Reward Pathway, Pharmacokinetics, Dopamine, Opioid Use, Addiction
- Medical subject headings
- Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANS-6637Drug
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
| Study group | Role | What they receive |
|---|---|---|
| ANS-6637 & Midazolam | Experimental | Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8 Receives: Drug: ANS-6637 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics - Time to Maximum Concentration of Midazolam Alone
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam Alone
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam Alone
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam Alone
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Plasma Exposure of Midazolam Alone
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam Alone
1-hydroxymidazolam plasma area under the concentration time curve (time 0-infinity). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Elimination of Midazolam Alone
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Elimination of 1-hydroxymidazolam Alone
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 1
Pharmacokinetics - Time to Maximum Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Plasma Exposure of Midazolam: Midazolam Plus Steady State ANS-6637
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
1-hydroxymidazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Elimination of Midazolam: Midazolam Plus Steady State ANS-6637
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Pharmacokinetics - Elimination of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Measured: Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2019
- Study start1 Mar 2019
- Primary completion9 Aug 2019
- Study completion30 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opiod Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Henry Masur, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831971
- Sponsor's protocol ID
- 190052
- Other IDs
- 19-CC-0052
- Status last verified
- 30 Dec 2019
- First submitted
- 5 Feb 2019
- Last updated
- 3 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diamond I, Yao L. From Ancient Chinese Medicine to a Novel Approach to Treat Cocaine Addiction. CNS Neurol Disord Drug Targets. 2015;14(6):716-26. doi: 10.2174/1871527314666150529144329.
PubMed 26022266Yao L, Fan P, Arolfo M, Jiang Z, Olive MF, Zablocki J, Sun HL, Chu N, Lee J, Kim HY, Leung K, Shryock J, Blackburn B, Diamond I. Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis. Nat Med. 2010 Sep;16(9):1024-8. doi: 10.1038/nm.2200. Epub 2010 Aug 22.
PubMed 20729865Volkow ND, Koob GF, McLellan AT. Neurobiologic Advances from the Brain Disease Model of Addiction. N Engl J Med. 2016 Jan 28;374(4):363-71. doi: 10.1056/NEJMra1511480. No abstract available.
PubMed 26816013
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers (SEARCH PK)
- ClinicalTrials.gov ID
- NCT03831971
- Acronym / sponsor ID
- 190052
- Conditions
- Opiod Use Disorder
- Keywords
- Reward Pathway, Pharmacokinetics, Dopamine, Opioid Use, Addiction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 9 Aug 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 6 Feb 2019 (actual)
- Results
- Posted 3 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ANS-6637 & Midazolam | Experimental | Drug: ANS-6637Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (21 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ANS-6637Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8 | Drug | ANS-6637 & Midazolam |
Primary outcome
Pharmacokinetics - Time to Maximum Concentration of Midazolam Alone
Time frame: Day 1
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam Alone
Time frame: Day 1
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam Alone
Time frame: Day 1
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam Alone
Time frame: Day 1
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Plasma Exposure of Midazolam Alone
Time frame: Day 1
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam Alone
Time frame: Day 1
1-hydroxymidazolam plasma area under the concentration time curve (time 0-infinity). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Elimination of Midazolam Alone
Time frame: Day 1
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Elimination of 1-hydroxymidazolam Alone
Time frame: Day 1
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Time to Maximum Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Plasma Exposure of Midazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
1-hydroxymidazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Elimination of Midazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Pharmacokinetics - Elimination of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
Time frame: Day 8
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26022266Diamond I, Yao L. From Ancient Chinese Medicine to a Novel Approach to Treat Cocaine Addiction. CNS Neurol Disord Drug Targets. 2015;14(6):716-26. doi: 10.2174/1871527314666150529144329.
- Background: PubMed 20729865Yao L, Fan P, Arolfo M, Jiang Z, Olive MF, Zablocki J, Sun HL, Chu N, Lee J, Kim HY, Leung K, Shryock J, Blackburn B, Diamond I. Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis. Nat Med. 2010 Sep;16(9):1024-8. doi: 10.1038/nm.2200. Epub 2010 Aug 22.
- Background: PubMed 26816013Volkow ND, Koob GF, McLellan AT. Neurobiologic Advances from the Brain Disease Model of Addiction. N Engl J Med. 2016 Jan 28;374(4):363-71. doi: 10.1056/NEJMra1511480. No abstract available.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henry Masur, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ANS-6637 in people with Opiod Use Disorder, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics - Time to Maximum Concentration of Midazolam Alone (time frame: Day 1). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03831971, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.