A Phase 1 Relative Bioavailability Study Comparing The Pharmacokinetics Of Aramchol Meglumine Granules For Oral Suspension To Aramchol Free Acid 300 mg Tablets In Healthy Volunteers
A Phase 1 Relative Bioavailability Study Comparing The Pharmacokinetics Of Aramchol Meglumine Granules For Oral Suspension To Aramchol Free Acid 300 mg Tablets In Healthy Volunteers
This is a Phase 1 Relative Bioavailability Study Comparing The Pharmacokinetics Of Aramchol Meglumine (AM) Granules For Oral Suspension To Aramchol Free Acid (AA) 300 mg Tablets In Healthy Volunteers
A single center, 3-period, open-label, crossover study in healthy male and female volunteers who will receive 2 single doses of Aramchol meglumine (AM) and 1 single dose of Aramchol free acid (AA) under fasting conditions.
A single 400 mg dose of Aramchol meglumine (AM; Test 1) will be administered to all study subjects in Period 1.
The second dose of Aramchol meglumine (AM) will be between 200 mg and 800 mg and will be selected after review of the pharmacokinetics (PK) from Period 1.
In Periods 2 and 3, study subjects will be randomized 1:1 to receive the second dose of Aramchol meglumine (AM; Test 2) in one period and a 300 mg tablet of Aramchol free acid (AA; Reference) in the other period. Each product will be given under fasting conditions. The study periods will be separated by a wash-out period of at least 14 days.
Inclusion Criteria:
Male or female subjects
Age between 18 and 45 years (inclusive of the date of signing the informed consent form)
Male subjects must be using two acceptable methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and up to the study completion visit
Female subjects who are not of reproductive potential. A female subject who is not of reproductive potential is defined as a subject who:
(i) has reached natural menopause (defined as at least 12 months of spontaneous amenorrhea); (ii) is at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (iii) has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying cause (e.g., anorexia nervosa).
Female subjects who are of reproductive potential and use reliable contraception method and/or are willing to use adequate birth control methods starting from at least 4 weeks prior to the screening visit and for the duration of the study through 30 days after the last dose of study drug
List of medically accepted contraceptive methods:
Physically and mentally healthy as judged by means of medical and standard laboratory examinations
Non-smokers or ex-smokers (stopped at least 12 months ago) and non-users of other nicotine containing products, confirmed by urine cotinine test
Body mass index (BMI) within the range (including the borders) of 18.0 to 29.9 kg/m2
Informed consent given in written form according to Section 5.3 of clinical study protocol
Exclusion Criteria:
Participation in another clinical study at the same time or within 90 days before the screening visit (calculated from the date of the final examination of the previous study)
Randomization into the present study more than once
Blood donation or blood loss including plasmapheresis of >500 mL within 90 days before screening visit
History of drug abuse or use of illegal drugs: use of soft drugs, marihuana within 6 months before screening visit or hard drugs, cocaine, amphetamines, phencyclidine within 1 year before screening visit
Alcohol abuse, regular use of more than 2 units of alcohol per day or 10 units per week or a history of alcoholism (one unit of alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits) or recovered alcoholics
Regular consumption of beverages or food containing methylxanthines (coffee, tea, cola, caffeine containing sodas, chocolate) equivalent to more than 500 mg methylxanthines per day
Positive drug screen
Positive alcohol test
Pregnant and/or nursing women. Positive pregnancy Human chorionic gonadotropin (hCG) test
Allergic diathesis or any clinically significant allergic disease (asthma or bronchial hyperreactivity)
Any history of drug hypersensitivity especially to the active and inactive ingredients of the Aramchol meglumine or Aramchol free acid preparations, including cholic acid
Presence or a history of clinically significant cardiovascular, renal, hepatic, pulmonary, metabolic, endocrine, hematological, gastrointestinal, neurological, psychiatric or other diseases
Clinically significant illness within 4 weeks before screening visit
Major surgery of the gastrointestinal tract except for appendectomy
Any chronic disease which might interfere with absorption, distribution, metabolism or excretion of the drug
History of difficulty in swallowing
Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies
Administration of depot injectable solutions or medications with a half-life > 1 week (including study medications) within 3 months before screening visit
Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before screening visit
Intake or administration of any oral, systemic or topical medication [including Over The Counter (OTC) medication] other than paracetamol and especially intake of antacids: aluminum hydroxide, magnesium hydroxide, and simethicone or herbal medication: St. John's wort, kava kava) within 2 weeks before screening visit
Vaccination within 14 days prior to screening visit
Medication with drugs known to alter the major organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within 60 days before screening visit
Systolic blood pressure outside the range of 100 to 140 mmHg and/or diastolic blood pressure outside the range of 60 to 90 mmHg
Pulse rate outside the range of 45 to 100 beats/min
Axillary body temperature outside the interval of 35.5 to 37.0°C
Any clinically significant abnormality of the resting 12-lead Electrocardiogram (ECG)
Laboratory values outside the normal range with clinical relevance
Special diet due to any reason (vegetarian)
Body weight loss of more than 10 kg in the last two months
History or presence of piercings in the mouth (tongue, lips) or wearing braces or dentures
Subjects who are known or suspected: