Pharmacokinetics of Single and Multiple Escalating Doses of Aramchol and Food Effect in Healthy Volunteers

NCT02374437 | Completed Phase 1

• 1 other identifier: Aramchol004
• Study Type: interventional
• Target: 66
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• 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: For each treatment period: 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.

• Area under the plasma concentration time curve (AUC)

  Part B: For each treatment period: 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.

• Maximum plasma concentration (Cmax)

  Part C: day 1 and day 10

• Area under the plasma concentration time curve (AUC)

  Part C: day 1 and day 10

Secondary Outcomes (6)

• 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 C:Dosing days 1-10

• Adverse event (AE) profile

  Part B: For each treatment period: 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.

• Adverse event (AE) profile

  Part C: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 C:Dosing days 1-10

• Clinical laboratory safety tests

  Part B: For each treatment period: 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.

Study Arms (8)

PART A (single dose)-200 mg

ACTIVE COMPARATOR

200 mg ARAMCHOL

Drug: Aramchol

PART A (single dose)-400 mg

ACTIVE COMPARATOR

400 mg ARAMCHOL

Drug: Aramchol

Part B ( food effect)- -Fasting

ACTIVE COMPARATOR

600 mg Aramchol tablets under fasting conditions (fasting for at least 10 hours before and 4 hours after dosing)

Drug: Aramchol

Part B ( food effect)- -Fed

ACTIVE COMPARATOR

600 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)

Drug: Aramchol

Part C ( multiple doses)- 200 mg

ACTIVE COMPARATOR

200 mg Aramchol tablets for ten consecutive days.

Drug: Aramchol

Part C ( multiple doses)- 400 mg

ACTIVE COMPARATOR

400 mg Aramchol tablets for ten consecutive days.

Drug: Aramchol

Part C ( multiple doses)- 600 mg

ACTIVE COMPARATOR

600 mg Aramchol tablets for ten consecutive days.

Drug: Aramchol

Part C ( multiple doses)- Placebo

PLACEBO COMPARATOR

Placebo tablets for ten consecutive days.

Drug: Placebo

Interventions

Aramchol DRUG

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 A (single dose)-200 mg; PART A (single dose)-400 mg; Part B ( food effect)- -Fasting; Part B ( food effect)- -Fed; Part C ( multiple doses)- 200 mg; Part C ( multiple doses)- 400 mg; Part C ( multiple doses)- 600 mg

Placebo DRUG

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 ( multiple doses)- Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy, males subjects between 18-50 years (inclusive)
• \<BMI\< 29.9kg/m2
• Non-smoking (by declaration) for a period of at least 3 months before screening visit.
• Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
• No significant abnormalities in ECG (e.g. prolonged QTC, 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 screen determined on Day (0) before dosing session(s)
• Negative HIV, hepatitis B or hepatitis C serology tests as evaluated at screening.
• Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• Subjects must agree to use adequate birth control measures (condom in combination with a spermicidal gel or foam) during the study and up to 15 days after the last study drug administration.
• Subjects must satisfy a medical examiner about their fitness to participate in the study.
• Subjects must provide written informed consent to participate in the study.

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 (such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc.) within 30 days prior to dosing.
• Known hypersensitivity and/or allergy to any drugs.
• Adherence (for whatever reason) to an abnormal diet during the 4 weeks prior to the study, or subjects with recent significant change in body weight
• Any acute illness (e.g. 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).
• Subjects who donated blood in the three months or received blood or plasma derivatives in the six months preceding study drug administration.
• Subjects with inability to communicate well with the investigators and CRC staff (i.e., language problem, poor mental development or impaired cerebral function).
• Inability to fast or consume the food provided in the study (including any known food allergies or food restrictions).
• Subjects who are non-cooperative or unwilling to sign consent form.

Sponsors & Collaborators

• Galmed Pharmaceuticals Ltd: lead

MeSH Terms

Interventions

aramchol

Study Officials

• Maya Halpern, MD

  GALMED PHARMCEUTICALS

  STUDY DIRECTOR

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: January 18, 2015
• First Posted: February 27, 2015
• Study Start: April 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 27, 2015

Record last verified: 2015-02