Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets

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:

• Combination of a barrier method and spermicides (film, jelly, foam): female/ male condoms with spermicides, as well as a diaphragm/ cervical cap/ contraceptive sponge with spermicides.
• Hormonal methods: combined estrogen/progestin injectable and oral contraceptives; progestin injectable and oral contraceptives; implants (Nexplanon®), vaginal ring (NuvaRing®), skin patch (Xulane®) and contraceptive injection (Depo-Provera®).
• Intrauterine devices (IUD): inert or copper IUD (ParaGard®), hormonal IUD (Mirena®, Skyla®, Kyleena®).
• 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:

• not to comply with the study directives
• not to be reliable or trustworthy
• not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they would agree to be exposed
• to be in such a precarious financial situation that they no longer are able to weigh up the possible risks of their participation and the unpleasantness they may be involved in
• subject is in custody or submitted to an institution due to a judicial order.