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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Aramchol; Drug: Aramchol; Drug: Aramchol

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel-Aviv, Israel, 64239
    • Tasmc Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo control single dose	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: 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
Experimental: Dose 1; Dose 30 mg	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: 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
Experimental: Dose 2; Dose 100 mg	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: 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
Experimental: Dose 3; Dose 300 mg	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: 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
Experimental: Dose 4; Dose 900 mg	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: 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
Experimental: Dose 1 repeated; Dose 30 mg for 4 days	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: 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
Experimental: Dose 2 repeated; Dose high for 4 days	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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Galmed Medical Reserch
• Investigators: Principal Investigator: Jacob Atsmon, M.D., Tasmc Clinical Research Center

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: October 19, 2008
• First Submitted That Met QC Criteria: October 20, 2008
• First Posted (Estimate): October 21, 2008

Study Record Updates

• Last Update Posted (Estimate): November 3, 2010
• Last Update Submitted That Met QC Criteria: November 2, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Obesity; Hypercholesterolemia; fatty liver; Phase-I; Part A: Healthy male volunteers Part B: Mildly overweight, otherwise healthy hypercholesterolemic male volunteers
• Additional Relevant MeSH Terms: Gastrointestinal Agents; Cholic Acids; Bile Acids and Salts
• Other Study ID Numbers: PROTOCOL No: TRC 037/10072