JOTROL PK, Safety, and Food Effect Assessment
Condition: Pharmacokinetics; Safety; Food-drug Interaction
Intervention: 200 mg resveratrol as JOTROL; 500 mg resveratrol as JOTROL; 700 mg resveratrol as JOTROL; 500 mg resveratrol as JOTROL administered to assess influence of food
Intervention description: Low (first) dose of single ascending dose study; Second (intermediate) dose of single ascending dose study; Third (highest) dose of single ascending dose study; 500 mg resveratrol as JOTROL administered to assess influence of food
Intervention MeSH terms: Resveratrol
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Type of Study: Single Ascending Doses (SAD) Study

      Objectives:

      To characterize the pharmacokinetic (PK) profile of JOTROL (resveratrol) following oral
      administration of SAD ranging from 200 mg up to a dose currently estimated at 1,000 mg, in
      healthy subjects.

      To evaluate the safety and tolerability of JOTROL To evaluate the effect of food on the PK
      profile of JOTROL. Study Design: Phase I, randomized, open-label, sequential SAD study with a
      food effect evaluation. Blood plasma and urine samples will be assessed for resveratrol and
      key metabolite content.

      Type of Control: No control Test Product: JOTROL (resveratrol) 100 mg resveratrol in 1000 mg
      softgel capsule for oral administration Dosage Regimen: Planned dose levels of resveratrol:
      200 mg, 500 mg, and 1,000 mg. Following completion of each dose level, PK, safety, and
      tolerability data will be evaluated; dose levels may be adjusted.

      Route of Administration: Oral gelcaps with water Number of Subjects: 24 subjects will be
      included in Part 1; only 16 subjects, who completed Part 1, will be included in Part 2.

      Subjects: Healthy, non-smoker, adult males or females, ≥ 18 and ≤ 75 years of age Study
      Duration: Participation of each subject in this study should last approximately 1 to 1.5
      months (for subjects participating in study Part 1 only) and 1.5 to 2 months (for subjects
      participating in both study parts).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Normal healthy male or female volunteers, non-smokers (no use of tobacco products
             within 3 months prior to screening), ≥ 18 and ≤ 75 years of age, with BMI > 18.5 and <
             30.0 kg/m 2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females

          2. Healthy as defined by:

               1. the absence of clinically significant illness and surgery within 4 weeks prior to
                  dosing. Subjects vomiting within 24 hours predose will be carefully evaluated for
                  upcoming illness/disease. Inclusion pre-dosing is at the discretion of the
                  Investigator.

               2. the absence of clinically significant history of neurological, endocrine,
                  cardiovascular, respiratory, hematological, immunological, psychiatric,
                  gastrointestinal, renal, hepatic, and metabolic disease as determined by the
                  Investigator.

          3. Females of childbearing potential who are sexually active with a male partner must be
             willing to use one of the following acceptable contraceptive methods throughout the
             study and for 30 days after the last study drug administration:

               1. intra-uterine contraceptive device without hormone release system placed at least
                  4 weeks prior to study drug administration;

               2. male condom with intravaginally applied spermicide starting at least 21 days
                  prior to study drug administration;

               3. sterile male partner (vasectomized since at least 6 months).

          4. Capable of consent

        Exclusion Criteria:

          1. Any clinically significant abnormality at physical examination, clinically significant
             abnormal laboratory test results or positive test for hepatitis B, hepatitis C, or HIV
             found during medical screening.

          2. Positive urine drug screen or urine cotinine test at screening.

          3. History of allergic reactions to resveratrol, polyphenols, other related drugs, .

             or to any excipient in the formulation

          4. Positive pregnancy test at screening.

          5. Breast-feeding subject.

          6. Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood
             pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or
             over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.

          7. History of significant alcohol abuse within 1 year prior to screening or regular use
             of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol
             per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).

          8. History of significant drug abuse within 1 year prior to screening or use of soft
             drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs
             (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and
             amphetamine derivatives) within 1 year prior to screening.

          9. Use of resveratrol for a medical condition or in the context of another clinical trial
             within a period of 30 days prior to the first dosing.

         10. Participation in a clinical research study involving the administration of an
             investigational or marketed drug or device within 30 days prior to the first dosing,
             administration of a biological product in the context of a clinical research study
             within 90 days prior to the first dosing, or concomitant participation in an
             investigational study involving no drug or device administration.

        Use of medications for the timeframes specified below, with the exception of medications
        exempted by the Investigator on a case-by-case basis because they are judged unlikely to
        affect the PK profile of the study drug or subject safety (e.g., topical drug products
        without significant systemic absorption):

          1. prescription medication within 14 days prior to the first dosing;

          2. over-the-counter products and natural health products (including herbal remedies,
             homeopathic and traditional medicines, probiotics, food supplements such as vitamins,
             minerals, amino acids, essential fatty acids, and protein supplements used in sports)
             within 14 days prior to the first dosing, with the exception of the occasional use of
             acetaminophen (up to 2 g daily);

          3. use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days
             prior to the first study drug administration, including St John's wort;

          4. depot injection or an implant of any drug within 3 months prior to the first dosing.

        12. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding
        volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL
        within 56 days prior to the first dosing.

        13. Any reason which, in the opinion of the Investigator, would prevent the subject from
        participating in the study.