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

G

Galmed Pharmaceuticals

Status and phase

Active, not recruiting
Phase 1

Conditions

Healthy

Treatments

Drug: Aramchol free acid
Drug: Aramchol meglumine

Study type

Interventional

Funder types

Industry

Identifiers

Details and patient eligibility

About

This is 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

Full description

A single center, 3-period, open-label, crossover study in healthy male and female volunteers who will receive 2 single doses of Aramchol meglumine and 1 single dose of Aramchol free acid under fasting conditions. A single 400 mg dose of Aramchol meglumine (Test 1) will be administered to all study subjects in Period 1. The second dose of Aramchol meglumine 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 (Test 2) in one period and a 300 mg tablet of Aramchol free acid (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.

Enrollment

16 estimated patients

Sex

All

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. Male or female subjects

  2. Age between 18 and 45 years (inclusive of the date of signing the informed consent form)

  3. 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

  4. 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).

  5. 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®).
  6. Physically and mentally healthy as judged by means of medical and standard laboratory examinations

  7. Non-smokers or ex-smokers (stopped at least 12 months ago) and non-users of other nicotine containing products, confirmed by urine cotinine test

  8. Body mass index (BMI) within the range (including the borders) of 18.0 to 29.9 kg/m2

  9. Informed consent given in written form according to Section 5.3 of clinical study protocol

Exclusion criteria

  1. 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)

  2. Randomization into the present study more than once

  3. Blood donation or blood loss including plasmapheresis of >500 mL within 90 days before screening visit

  4. 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

  5. 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

  6. Regular consumption of beverages or food containing methylxanthines (coffee, tea, cola, caffeine containing sodas, chocolate) equivalent to more than 500 mg methylxanthines per day

  7. Positive drug screen

  8. Positive alcohol test

  9. Pregnant and/or nursing women. Positive pregnancy hCG test

  10. Allergic diathesis or any clinically significant allergic disease (asthma or bronchial hyperreactivity)

  11. Any history of drug hypersensitivity especially to the active and inactive ingredients of the Aramchol meglumine or Aramchol free acid preparations, including cholic acid

  12. Presence or a history of clinically significant cardiovascular, renal, hepatic, pulmonary, metabolic, endocrine, hematological, gastrointestinal, neurological, psychiatric or other diseases

  13. Clinically significant illness within 4 weeks before screening visit

  14. Major surgery of the gastrointestinal tract except for appendectomy

  15. Any chronic disease which might interfere with absorption, distribution, metabolism or excretion of the drug

  16. History of difficulty in swallowing

  17. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies

  18. Administration of depot injectable solutions or medications with a half-life > 1 week (including study medications) within 3 months before screening visit

  19. Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before screening visit

  20. 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

  21. Vaccination within 14 days prior to screening visit

  22. Medication with drugs known to alter the major organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within 60 days before screening visit

  23. Systolic blood pressure outside the range of 100 to 140 mmHg and/or diastolic blood pressure outside the range of 60 to 90 mmHg

  24. Pulse rate outside the range of 45 to 100 beats/min

  25. Axillary body temperature outside the interval of 35.5 to 37.0°C

  26. Any clinically significant abnormality of the resting 12-lead Electrocardiogram (ECG)

  27. Laboratory values outside the normal range with clinical relevance

  28. Special diet due to any reason (vegetarian)

  29. Body weight loss of more than 10 kg in the last two months

  30. History or presence of piercings in the mouth (tongue, lips) or wearing braces or dentures

  31. 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Crossover Assignment

Masking

None (Open label)

16 participants in 3 patient groups

Subjects receiving a single 400 mg dose of Aramchol meglumine in Period 1
Experimental group
Description:
A single 400 mg dose of Aramchol meglumine will be administered to all study subjects in Period 1.
Treatment:
Drug: Aramchol meglumine
Subjects receiving a second dose of Aramchol meglumine or Aramchol free acid in Period 2
Active Comparator group
Description:
In Period 2, study subjects will be randomized 1:1 to receive Aramchol meglumine or 300 mg tablet of Aramchol free acid (Reference)
Treatment:
Drug: Aramchol meglumine
Drug: Aramchol free acid
Subjects receiving a second dose of Aramchol meglumine or Aramchol free acid in Period 3
Active Comparator group
Description:
In Period 3, study subjects will be randomized 1:1 to receive Aramchol meglumine or 300 mg tablet of Aramchol free acid (Reference)
Treatment:
Drug: Aramchol meglumine
Drug: Aramchol free acid

Trial contacts and locations

1

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Central trial contact

Yossi Gilgun-Sherki, PhD, MBA; Irit Glico-Kabir, PhD

Data sourced from clinicaltrials.gov

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