Food-drug Interaction, Pharmacokinetics, Safety
Conditions
Brief 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).
Interventions
DRUG200 mg resveratrol as JOTROL
Low (first) dose of single ascending dose study
DRUG500 mg resveratrol as JOTROL
Second (intermediate) dose of single ascending dose study
DRUG700 mg resveratrol as JOTROL
Third (highest) dose of single ascending dose study
DRUG500 mg resveratrol as JOTROL administered to assess influence of food
500 mg resveratrol as JOTROL administered to assess influence of food
Sponsors
National Institute on Aging (NIA)
Jupiter Orphan Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug administration up to 131 days | An adverse event (AE) was defined as any untoward medical occurrence (including clinically significant \[CS\] vital signs measurements or laboratory results) or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the course of the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. TEAEs includes both serious and non-serious TEAEs. |
| Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported. AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported and calculated as AUC0-t + Ct/Kel, where Ct is the last observed measurable concentration, AUC0-t is Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration and Kel is Elimination rate constant. |
| Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | AUC0-t was Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule. |
| Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | Cmax was the maximum observed plasma concentration obtained directly from the concentration versus time curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 | Cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts excreted over each collection interval. The amount excreted in urine for each time interval was calculated as the urine concentration multiplied by the urine volume. |
| Maximum Rate of Urinary Excretion (Rmax) for Resveratrol | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 | Maximum rate of urinary excretion, calculated by dividing the amount of drug excreted in each collection interval by the time over which it was collected. |
| Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | Tmax was time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. |
| Renal Clearance (CLr) for Resveratrol | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 | CLr was calculated as Ae0-t/AUC0-t (plasma) where t is Tlast. |
| Time of Rmax (Tmax) for Resveratrol | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 | Tmax was the time after administration of a drug when the Rmax is reached. |
| Residual Area for Resveratrol | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | Residual area for resveratrol in plasma was calculated and reported. The residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) where AUC0-t (h\*ng/mL) = area under the concentration-time curve from time zero to the last measurable concentration and AUC0-inf (h\*ng/mL) = area under the plasma concentration-time curve from time 0 to time of infinity. |
| Elimination Half-Life (T1/2 el) for Resveratrol | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | Elimination half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Elimination Rate Constant (Kel) for Resveratrol | Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 | Kel was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 21 January 2021 to 31 May 2021.
Pre-assignment details
A total of 83 healthy participants were screened, of which 29 participants were eligible for this study. Of 29 eligible participants, a total of 24 participants were treated in this single ascending dose study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A) gelcap, orally once on Day 1 in Study period 1 followed by 500 (5\*100) mg (Treatment B) gelcap, orally once on Day 1 in Study period 2 further followed by 700 (7\*100) mg (Treatment C) gelcap, orally, on Day 1 in Study period 3 in fasted conditions of Part 1 of the study, followed by JOTROL (resveratrol) 500 (5\*100) mg (Treatment D) gelcap, orally, once on Day 1 in fed condition in Study Period 4 of Part 2 of the study. There was a washout period of 14 days between each study period. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 Study Period 1 | Adverse Event | 3 | 0 | 0 | 0 |
| Part 1 Study Period 1 | Withdrawal by Subject | 2 | 0 | 0 | 0 |
| Part 1 Study Period 2 | Other | 0 | 1 | 0 | 0 |
| Part 1 Study Period 3 | Adverse Event | 0 | 0 | 1 | 0 |
| Part 1 Study Period 3 | Other | 0 | 0 | 2 | 0 |
| Part 2 Study Period 4 | Other | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 16 | 0 / 18 | 0 / 15 |
| other Total, other adverse events | 7 / 21 | 4 / 16 | 6 / 18 | 6 / 15 |
| serious Total, serious adverse events | 0 / 21 | 0 / 16 | 0 / 18 | 0 / 15 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
AUC0-t was Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 112.32 h*ng/mL | Geometric Coefficient of Variation 72.49 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 4796.08 h*ng/mL | Geometric Coefficient of Variation 29.58 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 11593.20 h*ng/mL | Geometric Coefficient of Variation 26.78 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 4550.27 h*ng/mL | Geometric Coefficient of Variation 27.58 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 16347.62 h*ng/mL | Geometric Coefficient of Variation 27.21 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 34854.48 h*ng/mL | Geometric Coefficient of Variation 31.49 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 15337.45 h*ng/mL | Geometric Coefficient of Variation 29.7 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 422.85 h*ng/mL | Geometric Coefficient of Variation 53.24 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 53351.47 h*ng/mL | Geometric Coefficient of Variation 20.04 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 29492.22 h*ng/mL | Geometric Coefficient of Variation 34.04 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 22845.47 h*ng/mL | Geometric Coefficient of Variation 29.36 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 785.29 h*ng/mL | Geometric Coefficient of Variation 51.52 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 14502.21 h*ng/mL | Geometric Coefficient of Variation 21.93 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 11775.27 h*ng/mL | Geometric Coefficient of Variation 28.51 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 263.75 h*ng/mL | Geometric Coefficient of Variation 65.72 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 31018.49 h*ng/mL | Geometric Coefficient of Variation 33.26 |
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported. AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported and calculated as AUC0-t + Ct/Kel, where Ct is the last observed measurable concentration, AUC0-t is Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration and Kel is Elimination rate constant.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The pharmacokinetic (PK) population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Number analyzed signifies to participants evaluable for given categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 214.73 hour*nanogram per milliliter (h*ng/mL) | — |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 4821.18 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.37 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 11668.98 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.75 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 4591.06 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.34 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 16390.55 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.25 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 35063.90 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.67 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 15387.06 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.76 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 499.73 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 56.54 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 53845.25 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.62 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 29570.84 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 34.08 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 22934.42 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.9 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 595.75 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.19 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 14528.02 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.95 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 11834.05 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.41 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 553.77 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.84 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 31133.94 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33.24 |
Primary
Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Cmax was the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 94.70 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 91.46 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 2292.84 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.69 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 6204.37 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 1649.08 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33.3 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 8334.08 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.84 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 16863.57 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.55 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 5340.95 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56.63 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 326.32 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 89.76 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 22856.79 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.23 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 14558.05 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46.33 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 7663.09 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 648.08 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 73.29 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-4'-Glucuronide | 3742.71 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.44 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Glucuronide | 4173.48 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 59.28 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol | 140.09 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 100.84 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) | Resveratrol-3-Sulfate | 10696.58 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 65.43 |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence (including clinically significant \[CS\] vital signs measurements or laboratory results) or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the course of the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. TEAEs includes both serious and non-serious TEAEs.
Time frame: From first dose of study drug administration up to 131 days
Population: The safety population was defined as all participants who received at least one dose of the study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participants |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Secondary
Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol
Cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts excreted over each collection interval. The amount excreted in urine for each time interval was calculated as the urine concentration multiplied by the urine volume.
Time frame: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol | 16927.35 nanogram (ng) | Geometric Coefficient of Variation 75.39 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol | 48454.76 nanogram (ng) | Geometric Coefficient of Variation 49.88 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol | 109323.50 nanogram (ng) | Geometric Coefficient of Variation 88.32 |
Secondary
Elimination Half-Life (T1/2 el) for Resveratrol
Elimination half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here overall number of participants analyzed included all participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Elimination Half-Life (T1/2 el) for Resveratrol | 1.26 hour | — |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Elimination Half-Life (T1/2 el) for Resveratrol | 2.36 hour | Geometric Coefficient of Variation 62.56 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Elimination Half-Life (T1/2 el) for Resveratrol | 1.56 hour | Geometric Coefficient of Variation 25.19 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Elimination Half-Life (T1/2 el) for Resveratrol | 1.47 hour | Geometric Coefficient of Variation 71.72 |
Secondary
Elimination Rate Constant (Kel) for Resveratrol
Kel was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here overall number of participants analyzed included all participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Elimination Rate Constant (Kel) for Resveratrol | 0.5520 1 per hour (1/h) | — |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Elimination Rate Constant (Kel) for Resveratrol | 0.2932 1 per hour (1/h) | Geometric Coefficient of Variation 48.7 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Elimination Rate Constant (Kel) for Resveratrol | 0.4436 1 per hour (1/h) | Geometric Coefficient of Variation 28.56 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Elimination Rate Constant (Kel) for Resveratrol | 0.4712 1 per hour (1/h) | Geometric Coefficient of Variation 71.72 |
Secondary
Maximum Rate of Urinary Excretion (Rmax) for Resveratrol
Maximum rate of urinary excretion, calculated by dividing the amount of drug excreted in each collection interval by the time over which it was collected.
Time frame: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Maximum Rate of Urinary Excretion (Rmax) for Resveratrol | 8791.49 nanogram per hour (ng/h) | Geometric Coefficient of Variation 82.45 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Maximum Rate of Urinary Excretion (Rmax) for Resveratrol | 26486.23 nanogram per hour (ng/h) | Geometric Coefficient of Variation 136.58 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Maximum Rate of Urinary Excretion (Rmax) for Resveratrol | 44737.57 nanogram per hour (ng/h) | Geometric Coefficient of Variation 90.97 |
Secondary
Renal Clearance (CLr) for Resveratrol
CLr was calculated as Ae0-t/AUC0-t (plasma) where t is Tlast.
Time frame: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Renal Clearance (CLr) for Resveratrol | 0.15 liter per hour (L/h) | Geometric Coefficient of Variation 112.22 |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Renal Clearance (CLr) for Resveratrol | 0.11 liter per hour (L/h) | Geometric Coefficient of Variation 63.04 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Renal Clearance (CLr) for Resveratrol | 0.14 liter per hour (L/h) | Geometric Coefficient of Variation 95.39 |
Secondary
Residual Area for Resveratrol
Residual area for resveratrol in plasma was calculated and reported. The residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) where AUC0-t (h\*ng/mL) = area under the concentration-time curve from time zero to the last measurable concentration and AUC0-inf (h\*ng/mL) = area under the plasma concentration-time curve from time 0 to time of infinity.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here overall number of participants analyzed included all participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Residual Area for Resveratrol | 5.48 percentage AUC | — |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Residual Area for Resveratrol | 4.56 percentage AUC | Geometric Coefficient of Variation 73.5 |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Residual Area for Resveratrol | 3.58 percentage AUC | Geometric Coefficient of Variation 38.56 |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Residual Area for Resveratrol | 2.29 percentage AUC | Geometric Coefficient of Variation 111.16 |
Secondary
Time of Rmax (Tmax) for Resveratrol
Tmax was the time after administration of a drug when the Rmax is reached.
Time frame: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Time of Rmax (Tmax) for Resveratrol | 0.793 hour |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Time of Rmax (Tmax) for Resveratrol | 0.551 hour |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Time of Rmax (Tmax) for Resveratrol | 0.698 hour |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol
Tmax was time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.
Time frame: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1
Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol | 0.999 hour |
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol | 1.003 hour |
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol | 1.025 hour |
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol | 1.497 hour |