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

This is a Phase I/II, four-parts study (Parts A to D) in HVs and subjects with AUD, evaluating the tolerability, safety, and pharmacokinetics/ pharmacodynamics (PK/PD) of 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 part, 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. Below is a short description of each part of the study.

* Part A - Single dose (\~ 24) HVs: At least four consecutive ascending dose cohorts (20 mg, 40, 80 and 160mg) will be included in this part of the study in accordance with a pre-defined dose escalating scheme (see Section 5.2). In each cohort, 6 HVs will receive a single dose of investigation medicine product (CMND-100) with the first cohort 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 (as defined in Section 11.1) or limiting toxicity (grade 2 and higher) in up to 2 subjects, as defined in Section 5.2) 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 information gathered in this part of the study will be reviewed by the DSMB and guide the doses to be studied in Parts B, C and D of this study. * Part B - Single dose (\~12) subjects with AUD: Once Part A has been completed and data analyzed and approved by the DSMB, Part B will be initiated and will consist of enrolling subjects with AUD in at least 2 consecutive ascending single dose cohorts using the highest tolerable doses found in Part A. The first cohort will start with the lower ascending dose. Six subjects will be dosed 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 (as defined in Section 11.1) or limiting toxicity (grade 2 and higher in up to 2 subjects, as defined in Section 5.2) are observed in this dose level, then the next 6 subjects are treated with the next escalated dose. For any grade 2 or higher toxicity in more of two subjects refer to Section 5.2. At the end of this part, real time PK data from the dose cohorts will be collected and analyzed and this information together with the safety information gathered in this part of the study and the data observed in Part A will be reviewed by the DSMB and will guide the dose to be studied in Part D of this study. * Part C - Multiple dose (18) HVs: Once Part A has been completed, the data analyzed 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 analyzed (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. * Part D - 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.