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JOTROL PK, Safety, and Food Effect Assessment

J

Jupiter Orphan Therapeutics

Status and phase

Completed
Phase 1

Conditions

Food-drug Interaction
Safety
Pharmacokinetics

Treatments

Drug: 700 mg resveratrol as JOTROL
Drug: 200 mg resveratrol as JOTROL
Drug: 500 mg resveratrol as JOTROL administered to assess influence of food
Drug: 500 mg resveratrol as JOTROL

Study type

Interventional

Funder types

Industry
NIH

Identifiers

NCT04668274
R44AG067907-01A1 (U.S. NIH Grant/Contract)
Protocol 202016

Details and patient eligibility

About

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).

Enrollment

24 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

  5. 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.

  6. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

24 participants in 4 patient groups

Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
Experimental group
Description:
Participants received JOTROL (resveratrol) 200 (2\*100) milligram (mg) (Treatment A), gelatin capsule (gelcap), orally, once on Day 1 in fasted conditions in Study Period 1.
Treatment:
Drug: 200 mg resveratrol as JOTROL
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
Experimental group
Description:
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A 14 days washout period was maintained in study period 1 and 2.
Treatment:
Drug: 500 mg resveratrol as JOTROL
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
Experimental group
Description:
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A 14 days washout period was maintained in study period 2 and 3.
Treatment:
Drug: 700 mg resveratrol as JOTROL
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Experimental group
Description:
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A 14 days washout period was maintained in study period 3 and 4.
Treatment:
Drug: 500 mg resveratrol as JOTROL administered to assess influence of food

Trial documents
3

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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