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

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

Primary Objectives:

1. 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)
2. To assess the pharmacokinetics of Aramchol at the administered doses

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

• Drug: Aramchol
  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)
  Other Names:

  • Aramchol
  • 3β-arachidylamido-7α,12α,dihydroxy 5β-cholan-24-oic acid)
  • fatty-acid bile-acid conjugate
• Drug: Aramchol
  Oral Aramchol at dose 30 mg to 900 mg
• Drug: Aramchol
  Oral Aramchol at doses 30 mg to 900 mg single dose and 30 mg and high dose for 4 days

• Placebo Comparator: Placebo
  Placebo control single dose
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 1
  Dose 30 mg
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 2
  Dose 100 mg
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 3
  Dose 300 mg
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 4
  Dose 900 mg
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 1 repeated
  Dose 30 mg for 4 days
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol
• Experimental: Dose 2 repeated
  Dose high for 4 days
  Interventions:

  • Drug: Aramchol
  • Drug: Aramchol

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.