A First in Human Study of CMND-100 in Healthy and Alcohol Use Disorder (AUD) Subjects

NCT05913752 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CM-CMND-001
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 4

Brief Summary

The primary objective of this study is to find the tolerable dose and characterize the safety and pharmacokinetics/ pharmacodynamics (PK/PD) of single and repeated dose of CMND-100 in Healthy Volunteers (HV) and Subjects with Alcohol Use Disorder (AUD). The secondary objective of this study is to preliminarily evaluate the efficacy of CMND-100 in reduction of drinking patterns and craving in subjects with moderate to severe AUD.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (7)

• Safety as Adverse Events Profile

  Incidence of adverse events and classification in terms of severity, causality and outcome

  up to 31 days

• Tmax

  Time to maximum plasma concentration

  up to 31 days

• Cmax

  Maximum plasma concentration

  up to 31 days

• AUC0-∞

  Area under the concentration-time curve from 0 minutes extrapolated to infinity

  up to 31 days

• t1/2

  Terminal elimination phase half-life expressed in time units

  up to 31 days

• Cl

  The volume of plasma cleared of the drug per unit time

  up to 31 days

• Vd

  The volume in which a drug is distributed

  up to 31 days

Secondary Outcomes (2)

• Part D only - Alcohol craving assessment using the Visual Analogue Scale of Craving (VAS)

  The change from pre-dose to Day 5 and Day 17.

• Part D only - Assessment of craving for alcohol using the Penn Alcohol Craving Scale (PACS)

  The change from pre-dose to Day 5 and Day 17 of the total score will be evaluated.

Other Outcomes (3)

• Assessment of subjective level of sleepiness using the Karolisnka Sleepiness Scale (KSS). (Exploratory Endpoint - 1)

  The change from pre-dose to Day 5 and Day 17.

• Assessment of depression symptoms using the Beck Depression Inventory (BDI-II) (Exploratory Endpoint - 2)

  The change from pre-dose to Day 5 and Day 17.

• Evaluation of alcohol consumption using Alcohol Timeline Follow-Back (TLFB) (Exploratory Endpoint - 3)

  The change from pre-dose to post-dose Day 5 and Day 17.

Study Arms (4)

Healthy Subjects - Part A

OTHER

Part A: Single dose (\~ 24 ) Healthy Volunteers: At least four consecutive ascending dose cohorts (20 mg, 40, 80 and 160 mg) will be included in this part of the study in accordance with a pre-defined dose escalating scheme. In each cohort, 6 HVs will receive a single dose of investigation medicine product (CMND-100) starting with the lowest dose of 20 mg. Once dosed, the subjects will be sampled for PK for 24 hours following dosing and will be monitored for drug effects with a physical examination at the end of 24 hours after dosing and daily monitored for safety for a period of 1 week following dosing. Assuming no serious adverse reactions or limiting toxicity (grade 2 and higher) in up to 2, subjects are observed in this dose level, then the next 6 subjects are treated with the next escalated dose, in accordance with a pre-defined dose escalating scheme. The DSMB will review results after each cohort and guide doses to be studied in Parts B, C and D.

Drug: CMND-100

AUD Subjects - Part B

OTHER

Single dose (\~12): After DSMB review of part A, AUD subjects will be enrolled in at least 2 consecutive ascending single dose cohorts using the highest tolerable doses from Part A. The first cohort (n=6) will start with the lower ascending dose and sampled for PK for 24 hours following dosing and will be monitored for drug effects with a physical examination at the end of 24 hours after dosing and daily monitored for safety for a period of 1 week following dosing. Assuming no serious adverse reactions or limiting toxicity are observed in this dose level, then the next 6 subjects are treated with the next escalated dose. At the end of this part, real time PK data from the dose cohorts will be collected and analyzed. PK and safety information from this part of the study and from Part A will be reviewed by the DSMB and will guide the dose to be studied in Part D.

Drug: CMND-100

AUD Subjects - Part C

PLACEBO COMPARATOR

Multiple dose (18) HVs: Once Part A has been completed, the data analysed and approved by the DSMB, Part C will be initiated. This part will consist of a repeated-dose cohort based on the higher tolerable dose found in Part A. HVs will be randomized into either the treatment or the placebo arm at a ratio of 2:1 (12 subjects treated with the investigation product and 6 subjects receiving placebo) and will receive the drug/placebo at a daily basis for a total of 5 consecutive days. Each subject will be sampled for PK for 24 hours after first and last dosing and will be daily monitored for drug effects and safety throughout the study period and until 1 week after the last dosing. Real time PK data will be collected and results analysed (as defined in Section 5.2). The PK and safety information gathered from in this part of the study will be evaluated by the DSMB and will guide the dose to be studied in Part D of this study.

Drug: CMND-100

AUD Subjects - Part D

OTHER

Multiple dose (18) subjects with AUD: Once Part B and Part C has been completed, the data analyzed and approved by the DSMB, Part D will be initiated. This part will consist of a repeated-dose cohort, based on the higher tolerable dose found in Part C and considering the dose effects found in Part B. Subjects will be randomized into either the treatment or the placebo arm at a ratio of 2:1 (12 subjects treated with the investigation product and 6 subjects receiving placebo) and will receive the drug/placebo at a daily basis for a total of 5 consecutive days. Each subject will be sampled for PK for 24 hours after first and last dosing and will be daily monitored for drug effects and safety throughout the study period and until 1 week after the last dosing. The PK and safety information gathered from in this part of the study will be evaluated by the DSMB.

Drug: CMND-100

Interventions

CMND-100 DRUG

The investigational product CMND-100 consists of gelatin capsules, each containing the active ingredient (either 20 or 60 mg) 5-methoxy-2-aminoindane (MEAI) and excipients (stabilizers). MEAI is a psychoactive compound of the aminoindane class

Also known as: MEAI

AUD Subjects - Part B; AUD Subjects - Part C; AUD Subjects - Part D; Healthy Subjects - Part A

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Clearmind Medicine Inc.: lead

Study Sites (4)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

RECRUITING

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

RECRUITING

Hadassah Medical Center

Jerusalem, 91120, Israel

RECRUITING

Tel-Aviv Sourasky Medical Center (TASMC)

Tel Aviv, 6423906, Israel

RECRUITING

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parts C and D are randomized, double-blind, placebo-controlled.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single and repeated doses of CMND-100. Parts A and B are open-label, non-controlled parts, in which HVs and subjects with AUD respectively will be treated with single, ascending dose cohorts of CMND-100, for evaluation of tolerability, safety and PK/PD. Parts C and D are randomized, double-blind, placebo-controlled parts, in which HVs and subjects with AUD respectively will be treated with repeated doses of CMND-100, for evaluation of safety, PK/PD and preliminary efficacy.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: June 22, 2023
• Study Start: April 30, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (2); IL (2)