Pharmacokinetics of Single and Multiple Escalating Doses of Aramchol Administered Under Fed Conditions in Healthy Chinese Volunteers

NCT02803996 | Completed Phase 1

• 1 other identifier: Aramchol 015
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-site, randomized, double-blind, double dummy, placebo-controlled single and multiple doses study of Aramchol in healthy Chinese volunteers. The subject population that was enrolled for Aramchol 004 was not specifically designed to understand the PK profile of Aramchol in subjects of Chinese descent. Therefore, this study (Aramchol 015) has been undertaken to ascertain the PK profile of Aramchol following single and multiple doses in a Chinese population under fed conditions utilizing the light breakfast from Aramchol 004. This study will consist of two parts and the subjects will be assigned to two parts. In each part of the study, subjects will be enrolled in the study within 28 days of screening.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration (Cmax)

  Part A:Pre-dose (within 60 min before dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 30, 36, 48(±60 min), 72 (±60 min), 96 (±60 min), 144 (±60 min) hours post-dose.Part C: Dosing days 1-10

• Area under the plasma concentration time curve (AUC)

  Part A:Pre-dose (within 60 min before dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 30, 36, 48(±60 min), 72 (±60 min), 96 (±60 min), 144 (±60 min) hours post-dose.Part C: Dosing days 1-10.

• Maximum plasma concentration (Cmax)

  Part B: Day 1 and day 10

• Area under the plasma concentration time curve (AUC)

  Part C: Day 1 and Day 10

Secondary Outcomes (4)

• Adverse Event (AE) Profile

  Part A:Pre-dose (within 60 min before dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 30, 36, 48(±60 min), 72 (±60 min), 96 (±60 min), 144 (±60 min) hours post-dose. Part B:Dosing days 1-10

• Adverse Event (AE) Profile

  Part B: Dosing days 1 and 2: pre-dose (within 60 min before first dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18 and 24 (before second dosing) hours after drug administration+ day 3-10

• Clinical Laboratory Safety Tests

  Part A:Pre-dose (within 60 min before dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 30, 36, 48(±60 min), 72 (±60 min), 96 (±60 min), 144 (±60 min) hours post-dose. Part B:Dosing days 1-10

• Clinical Laboratory Safety Tests

  Part B:Dosing days 1 and 2: pre-dose (within 60 min before first dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18 and 24 (before second dosing) hours after drug administration+ day 3-10

Study Arms (6)

Part A- Single Dose- 400 mg Aramchol

ACTIVE COMPARATOR

Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo.

Drug: Aramchol

Part A- Single Dose- 600 mg Aramchol

ACTIVE COMPARATOR

Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo.

Drug: Aramchol

Part A-Single Dose-Placebo

PLACEBO COMPARATOR

Part A: Subjects will receive a single dose of 400 mg Aramchol, 600 mg Aramchol or placebo.

Drug: Placebo

Part B-Multiple Dose-400 mg Aramchol

ACTIVE COMPARATOR

Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days.

Drug: Aramchol

Part B-Multiple Dose-600 mg Aramchol

ACTIVE COMPARATOR

Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days.

Drug: Aramchol

Part B-Multiple Dose-Placebo

PLACEBO COMPARATOR

Part B: Subjects will receive multiple doses of 400 mg Aramchol, 600 mg Aramchol or placebo tablets for 10 consecutive days.

Drug: Placebo

Interventions

Aramchol DRUG

Part A: Aramchol oral tablets at 400 mg or 600 mg single dose Part B: Aramchol oral tablets at 400 mg or 600 mg multiple dose for 10 consecutive days.

Part A- Single Dose- 400 mg Aramchol; Part A- Single Dose- 600 mg Aramchol; Part B-Multiple Dose-400 mg Aramchol; Part B-Multiple Dose-600 mg Aramchol

Placebo DRUG

Part A: Placebo oral tablets single dose Part B: Placebo oral tablets multiple dose for 10 consecutive days.

Part A-Single Dose-Placebo; Part B-Multiple Dose-Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects, born in China, both parents of Chinese descent, aged at screening between 18-50 years old (inclusive), and having not lived outside of China for more than 10 years (in total, confirmed by verbal report).
• BMI ≥ 18.0 and ≤ 30.0.
• Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and physical examination.
• No significant abnormalities in ECG (eg, prolonged QTcF, prolonged PR interval) done at screening and on Days (0) before dosing session.
• No clinically significant abnormalities in hematology, blood chemistry, or urinalysis lab tests at screening.
• No known history of alcohol or drug abuse. Subjects with negative urinary drugs of abuse (DOA) screen determined on Day (0) before dosing session(s).
• Negative human immunodeficiency virus (HIV), hepatitis B, and hepatitis C serology tests as evaluated at screening.
• Negative urine pregnancy tests at screening and at check-in (women of childbearing potential only).
• Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• All subjects must agree to use a highly effective method of birth control during the study and up to 15 days after the last study drug administration. A highly effective method of birth control is considered to be one of the following:
• An oral or implanted hormonal method of contraception (if it had been used for ≥3 months prior to study drug administration) while also using a barrier method (ie, condom or diaphragm)
• A hormone or copper intrauterine device if it had been in place for ≥3 months prior to study drug administration (subjects using nonhormonal or copper intrauterine devices were also required to use a barrier method of contraception)
• A vasectomized partner
• Total abstinence is acceptable; however, the subject is required to use a highly effective method of contraception if the subject decides subsequently not to abstain
• Periodic abstinence around ovulation is not considered acceptable

You may not qualify if:

• Documented history or on-going symptoms of any gastrointestinal disorder involving motility, gastric acid or gastric emptying or malabsorption, including but not limited to, peptic ulcer disease, gastroesophageal reflux, dyspepsia, gastroparesis, chronic diarrhea, chronic constipation, gall bladder disease, pancreatitis, lactose intolerance and celiac disease.
• History of esophageal, gastric, biliary, or intestinal surgery (excluding herniotomy and appendectomy which are not related to gastrointestinal disorders).
• Known history of significant medical disorder, which in the investigator's judgment contraindicates administration of the study medications.
• Any clinically significant abnormality upon physical examination or in the clinical laboratory tests at screening visit.
• Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal or dietary supplements within 14 days prior to dosing. Paracetamol or ibuprofen for symptomatic relief of pain is allowed until 24 hours prior to the study drug administration.
• Subjects who have taken anticholinergic or other drugs known to affect gastrointestinal motility within 7 days prior to the first dosing.
• Treatment with any drugs with known hepatic enzyme-inducing or inhibiting agents (eg, barbiturates, phenothiazines, cimetidine, carbamazepine) within 30 days prior to dosing.
• Known clinically significant hypersensitivity and/or allergy to any drugs.
• Subjects with recent significant change in body weight (±10% within 3 months of screening).
• Any acute illness (eg, acute infection) within 48 hours prior to the first study drug administration, which is considered of significance by the Principal Investigator.
• Participation in another clinical trial with drugs, received within 3 months prior to dosing (calculated from the previous study's last dosing date).
• Female subjects who are pregnant or breastfeeding.
• Subjects who donated blood in the three months or received blood or plasma derivatives in the six months preceding study drug administration.
• Inability to fast or consume the food provided in the study (including any clinically significant known food allergies or food restrictions).
• Subjects who are non-cooperative, unwilling or unable to communicate with the investigators and site staff (ie, language problem, poor mental development or impaired cerebral function).

Sponsors & Collaborators

• Galmed Pharmaceuticals Ltd: lead
• WCCT Global: collaborator
• Alpha IRB: collaborator
• Analyst Research Laboratories: collaborator
• Kramer Consulting, LLC: collaborator
• Diamond Pharma Services Regulatory Affairs Consultancy: collaborator

Study Sites (1)

WCCT Global, LLC.

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

aramchol

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 17, 2016
• Study Start: May 1, 2016
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: December 21, 2016

Record last verified: 2016-12

Locations

US (1)