Pharmacokinetics of Single and Multiple Escalating Doses of Aramchol and Food Effect in Healthy Volunteers
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-site, randomized, partly double-blind, placebo-controlled study of Aramchol
      in sixty six (66) healthy male volunteers.

      In each part of the study subjects will be enrolled in the study within 28 days before drug
      administration(s).

      The study will consist of three parts and the subjects will be assigned to three Parts.
    

Detailed description: 
      This is a single-site, randomized, partly double-blind, placebo-controlled study of Aramchol
      in sixty six (66) healthy male volunteers.

      In each part of the study subjects will be enrolled in the study within 28 days before drug
      administration(s).

      The study will consist of three parts and the subjects will be assigned to three Parts as
      follows:

      Part A - single escalating doses:

      The purpose of this part is to evaluate the pharmacokinetics, safety and tolerability of
      Aramchol tablets at single doses of either 200 mg or 400 mg.

      Twelve (12) subjects will be randomized to receive , following an overnight 10 hours fast, a
      single dose of either:

        -  Administration A: 1×200 mg Aramchol tablet (6 subjects)

        -  Administration B: 1×400 mg Aramchol tablet (6 subjects) Subjects will be admitted to the
           Clinical Research Center (CRC) in the evening before study drug administration (Day 0)
           and will remain in-house for 36 hours after dosing. Blood samples for Aramchol
           concentrations will be drawn for 36 hours at designated time points as described below.
           Additional ambulatory samples will be collected at 48, 72, 96 and 144 hours post-dose.
           Subjects will be continuously monitored for safety.

      An End-of Study/Safety Follow-up visit will take place on the last PK sampling day, i.e. 144
      hours post-dose.

      Part B - food effect:

      The purpose of this part is to evaluate the effect of high fat high calorie meal on the
      pharmacokinetics of a single dose of Aramchol and to assess the safety and tolerability of a
      single 600 mg dose.

      This part is designed as a randomized, two period crossover food-effect study.

      Eighteen (18) subjects will be randomized to receive one of two administration sequences (C-D
      or D-C) as follows:

        -  Administration C: 1×200 mg +1×400 mg Aramchol tablets under fasting conditions (fasting
           for at least 10 hours before and 4 hours after dosing)

        -  Administration D: 1×200 mg +1×400 mg Aramchol tablets under fed conditions (fasting for
           at least 10 hours before dosing, consumption of a high calorie high fat meal within 30
           minutes prior to drug administration and no food for additional 4 hours after dosing) In
           each period of this part, subjects will be admitted to the Clinical Research Center
           (CRC) in the evening before study drug administration (Day 0) and will remain in-house
           for 36 hours after dosing. Blood for Aramchol concentrations will be drawn for 36 hours
           at designated time points as described below. Additional ambulatory samples will be
           collected at 48, 72, 96 and 144 hours post-dose. Subjects will be continuously monitored
           for safety.

      There will be a wash-out period of at least 14 days between each dosing session.

      An End-of Study/Safety Follow-up visit will take place on the last PK sampling day of the
      second dosing period, i.e. 144 hours after second dose.

      The PK profile of subjects who received administration C (i.e. 600 mg Aramchol tablet under
      fasting conditions) will be compared with that of subjects who received 200 and 400 mg
      Aramchol tablet under fasting conditions in Part A.

      Part C - multiple doses:

      The purpose of this part is to evaluate the pharmacokinetics, safety and tolerability of
      Aramchol tablets at multiple administrations of 3 different doses.

      This part is designed as a randomized, double blind, double-dummy, placebo-controlled
      multiple-dose study.

      Thirty six (36) subjects will participate in this part and will be equally randomized to
      receive either 200 mg, 400 mg, 600 mg or placebo tablets for ten consecutive days. Drug
      administration will be preceded by a light breakfast consumed within 1 hour prior to dosing
      (the composition of which is described in Appendix III). All drugs will be administered by
      the study staff except Dose No. 6 which the subjects will take at home.

      In order to maintain blinding, all subjects will receive two tablets on each dosing,
      according to the following administrations:

        -  Administration E: 1×200 mg Aramchol tablet + 1×400 mg Placebo tablet

        -  Administration F: 1×200 mg Placebo tablet + 1×400 mg Aramchol tablet

        -  Administration G : 1×200 mg Aramchol tablet + 1×400 mg Aramchol tablet

        -  Administration H: 1×200 mg Placebo tablet + 1×400 mg Placebo tablet

      Treatment assignment will be as follows:

      Subjects will be admitted to the Clinical Research Center (CRC) in the evening before the
      first study drug administration (Day 0) and will remain in-house for 24 and 36 hours after
      first (Day 1) and last (Day 10) doses, respectively. PK blood samples will be drawn on Day 1
      for 24 hours at designated time points as described below. Additionally, ambulatory pre-dose
      (trough) samples will be drawn before dosing on Days 2, 3, 4, 5, 7, 8, and 9. On Day 10 blood
      samples will be collected for 36 hours at designated time points as described below and
      during additional ambulatory visits at 48, 96, 120, 144, 168 and 192 hours post-dose.

      Subjects will be continuously monitored for safety. An End-of Study/Safety Follow-up visit
      will take place on the last PK sampling day of the study, i.e. 144 hours (for Parts A and B)
      and 192 hours (for Part C) after the last dose administration.
    

Intervention name(s): Aramchol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): PART A: Subjects will receive single dose of 200 or 400 mg Aramchol PART B: Subjects will receive single dose of 600 mg Aramchol under fasting or fed conditions ( following a crossover between the groups) PART C: subjects will be equally randomized to receive either 200 mg, 400 mg, 600 mg or placebo tablets for ten consecutive days.; PART C: subjects will be equally randomized to receive either 200 mg, 400 mg, 600 mg or placebo tablets for ten consecutive days.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)