CMND-100 for healthy volunteers and people with alcohol use disorder

A Phase I/II Single and Multiple Dose Tolerability, Safety and Pharmacokinetic Study of CMND-100 in Healthy Volunteers and Subjects With Alcohol Use Disorder (AUD)

This trial will test single and repeated doses of an experimental medicine called CMND-100 in healthy volunteers and in people with moderate to severe alcohol use disorder to find safe doses and see if it reduces drinking and craving.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Clearmind Medicine Inc. (Industry-sponsored)
• Drugs / interventions: Imatinib
• Locations: 4 sites (New Haven, Connecticut and 3 other locations)
• Trial ID: NCT05913752 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, four-part study enrolls both healthy volunteers and people with alcohol use disorder to characterize safety, tolerability, and pharmacokinetics/pharmacodynamics of CMND-100 after single and repeated dosing. Parts A and B are open-label, single ascending dose cohorts in healthy volunteers and AUD subjects respectively to identify tolerable dose ranges and collect PK/PD data. Parts C and D are randomized, double-blind, placebo-controlled repeated-dose cohorts in healthy volunteers and AUD subjects respectively to further evaluate safety, PK/PD, and preliminary efficacy on drinking behavior and craving. Dosing cohorts escalate (e.g., 20–160 mg in early cohorts), with intensive PK sampling and short-term safety monitoring after dosing.

Who should consider this trial

Good fit: Adults aged 18–60 with moderate to severe alcohol use disorder who meet the trial’s medical and contraceptive requirements, weigh over 60 kg with BMI 18–35, and are medically stable may be eligible.

Not a fit: People outside the 18–60 age or BMI/weight limits, those who are pregnant or breastfeeding, have significant uncontrolled medical conditions or take contraindicated medications, or who have only mild AUD may not benefit from or be eligible for this study.

Why it matters

Potential benefit: If successful, CMND-100 could provide a new, well-tolerated medication option that reduces alcohol use and craving in people with moderate to severe AUD.

How similar studies have performed: This is a first-in-human trial of CMND-100 so direct human data are lacking, though other experimental medications targeting craving and drinking have shown mixed but sometimes promising early results.

Eligibility criteria

Inclusion Criteria:

All Subjects

* Signed informed consent prior to any study-related procedures,
* Subjects understand the nature and the procedures related with the study design of the trial and accept to fulfill all activities related to this trial,
* Subjects 18 to 60 years of age,
* Body mass index between 18 and 35 kg/m2, with a weight above 60 kg.
* No (history of) clinically significant conditions and/or concomitant medications which in the opinion of the investigator could endanger the safety of the subject or impact the validity of the study results,
* Male subjects who wish use condoms for the duration of the study and for a suitable time period after the last drug dose (e.g., 5 half-lives),
* Female subjects who are not pregnant or breast-feeding or who do not wish to become pregnant during the period of the clinical study and for three months later,
* Female subjects of childbearing potential (less than 24 months after the last menstrual cycle) who use adequate contraceptive methods. Adequate contraceptive methods may include any approved method of birth control such as combined estrogen and progestogen containing hormonal contraception, associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intra-uterine devices, condoms, abstinence or vasectomized partner. Contraception should be maintained until study end.

Additional Criteria for AUD Subjects

Treatment seeking subjects with AUD meeting DSM-5 criteria as assessed by SCID by qualified medical staff and:

* Consumed at least 4 binge drinking days (i.e. ≥ 5 standard drinks in a day for men or ≥ 4 standard drinks in a day for women) in the month prior to screening.
* A desire to reduce or stop drinking.
* Stable housing in the 3 months prior to screening with no foreseeable risk to lose this in the 3 months after screening,
* Agree to abstain from new/additional psychotropic medications, except for benzodiazepines as rescue medication prescribed by the PI or a stable dose of psychotropic medications in the 14 days (or 5 half-lives; whichever is longer) prior to enrollment/randomization with the intention to continue this medication during the study.

Exclusion Criteria All Subjects

* The subject has a clinically significant history of a disease or a disorder that could interfere with the interpretation of the results or could increase the risk to the subject all according to the opinion of the PI,
* Subject has a substance use disorder at time of screening (except for alcohol use in AUD subjects and nicotine use disorders),
* Subjects with cannabis or other drug use for at least 5 half-lives prior to screening, including nicotine use (i.e., subjects must abstain from nicotine use for at least five half-lives prior to screening).
* Subjects with symptoms of alcohol withdrawal or intoxication at time of screening (assessed using CIWA-Ar tool). if medically appropriate, intoxicated individuals will be provided transportation home while those experiencing alcohol withdrawal will be referred to an appropriate level of care.
* Subjects with history of seizures or epilepsy,
* Current or past history of Major Depressive Disorder (MDD) (within past 1 years), Bipolar Disorder, Schizophrenia, suicidal ideation (within past 2 years) or suicide attempts in the past 2 years,
* Uncontrolled inter-current illness (i.e., active infection),
* Clinically significant abnormal vital signs (e.g., systolic blood pressure ≥139 mmHg, diastolic blood pressure ≥90 mmHg, heart rate \>90 beats per minute) at separate three measures before dosing,
* Clinically significant abnormal ECG parameters, including subjects with QTc greater than 450 msec.
* Clinically significant abnormal liver functions (ALT and AST), higher than three times the upper normal amount, clinically significant abnormal Hb, and/or clinically significant laboratory abnormalities (e.g., abnormal renal function, electrolyte derangements, etc.)
* Subjects who take, or are planning to take, any prescription or non-prescription medications, within at least 14 days (or 5 half-lives; whichever is longer) prior to enrollment/randomization, and for the entire duration of the study including: antipsychotic and mood stabilizing medications (including SSRIs such as Fluoxetine and Paroxetine, SNRIs and trazodone), OCT1 and OCT2 substrates (such as Metformin, Cisplatin, Imatinib, Procainamide, Citalopram, Cimetidine, Quinidine), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) or lithium, serotonin-acting herbal medicines and supplements, dietary supplements (such as 5-hydroxy-trypthophan or St. John Wort), and enzyme altering agents (such as and/or grapefruit juice and/or rifampin, barbiturates, phenothiazines, cimetidine, etc.) or any other medications that may have significant interaction with the study medication,
* Received an experimental drug or used an experimental medical device within 1 month or within a period \<5 times the drug's half-life for small molecules, or 3 months for biologics, whichever is longer, before the study drug is administered for the first time,
* Donated blood within 90 days or plasma within 30 days of study dosing,
* Any subject who may not be able to fulfill the study requirements per the investigator's clinical judgement.

Additional Criteria for Healthy Subjects

• Subject is unable to abstain from ingesting alcohol for 72 hours prior to dosing.

Where this trial is running

New Haven, Connecticut and 3 other locations

• Connecticut Mental Health Center — New Haven, Connecticut, United States (Recruiting)
• Johns Hopkins Bayview Medical Center — Baltimore, Maryland, United States (Recruiting)
• Hadassah Medical Center — Jerusalem, Israel (Recruiting)
• Tel-Aviv Sourasky Medical Center (TASMC) — Tel Aviv, Israel (Recruiting)

Conditions Alcohol Use Disorder