A Phase 1 Single and Multiple-Dose Study of Aramchol in Healthy Male Volunteers

Study Overview
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Brief Summary
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Escalating Single and Multiple-Dose Study of Aramchol in Healthy Male Volunteers. Primary Objectives: To assess and characterize the safety and tolerability of Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B) To assess the pharmacokinetics of Aramchol at the administered doses

Detailed Description
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Number of Subjects: Total: A total of 46 healthy subjects will be enrolled. Part A: Sixteen (16) subjects will participate in four, 8-person dosing periods. Each cohort will be alternately dosed twice. Part B: Thirty (30) subjects will be enrolled in two, 15-person dose-ascending cohorts. Main Inclusion Criteria: Part A: Healthy male volunteers aged 18-50 (inclusive) years who have provided written informed consent Part B: Mildly overweight (25<BMI<33), with fasting cholesterol levels of 200-300 mg/% or LDL 100-180 mg/% and triglycerides < 200 mg/%, otherwise healthy male volunteers aged 18-50 (inclusive) years, who have provided written informed consent

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Escalating Single and Multiple-Dose Study of Aramchol in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Aramchol
* Drug: Aramchol
* Drug: Aramchol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Healthy male volunteers aged 18-50 (inclusive) years who have provided written informed consent Part B: Mildly overweight (25<BMI <33), with fasting cholesterol levels of 200-300 mg/% or LDL 100-180 mg/% and triglycerides < 200 mg/%, otherwise healthy male volunteers aged 18-50 (inclusive) years, who have provided written informed consent Major Exclusion Criteria: History of significant neurological (including history of seizures or EEG abnormalities), renal, cardiovascular (including known structural cardiac abnormalities or hypertension), respiratory (asthma), endocrinological, gastrointestinal, hematopoietic disease, neoplasm, psychological (marked anxiety, tension or agitation) or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications. History of drug or alcohol abuse. Known allergy to any drug. Known allergy to any drug. Clinically significant abnormalities found in the screening physical exam. Significant abnormalities in clinical laboratory parameters (hematology, biochemistry, urinalysis) determined within 40 days of the start of the study and on Day (-1) before first dosing session. Parameters to be measured are those shown in Appendix 2.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo control single dose | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at dose 30 mg to 900 mg<br>Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 1<br>Dose 30 mg | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at dose 30 mg to 900 mg<br>Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 2<br>Dose 100 mg | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at dose 30 mg to 900 mg<br>Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 3<br>Dose 300 mg | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at dose 30 mg to 900 mg<br>Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 4<br>Dose 900 mg | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at dose 30 mg to 900 mg<br>Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 1 repeated<br>Dose 30 mg for 4 days | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|
| Experimental: Dose 2 repeated<br>Dose high for 4 days | Drug: Aramchol<br>* 1.Aramchol in 16 healthy male subjects at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, otherwise healthy male subjects receiving multiple doses (Part B)<br>* Other names: fatty-acid bile-acid conjugate;Drug: Aramchol<br>* Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability and Pharmacokinetics of Aramchol at single doses ranging between 30 and 900 mg (Part A) and in 30 overweight, mildly hypercholesterolemic, subjects receiving multiple doses (Part B) |  | day 1 to 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess and characterize the drug effect on lipid profile and functional pharmacodynamics following single and multiple dose administrations. |  | day 1 to 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase-I, Hypercholesterolemia, Obesity, fatty liver, Part A: Healthy male volunteers Part B: Mildly overweight, otherwise healthy hypercholesterolemic male volunteers