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| ID | Type | Description | Link |
|---|---|---|---|
| R44AG067907-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Experimental | 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. |
|
| Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | Experimental | 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. |
|
| Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | Experimental | 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. |
|
| Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 200 mg resveratrol as JOTROL | Drug | Low (first) dose of single ascending dose study |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose of study drug administration up to 131 days |
| 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. | 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 |
| 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. | 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 |
| Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
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
Healthy as defined by:
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:
Capable of consent
Exclusion Criteria:
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.
Positive urine drug screen or urine cotinine test at screening.
History of allergic reactions to resveratrol, polyphenols, other related drugs, .
or to any excipient in the formulation
Positive pregnancy test at screening.
Breast-feeding subject.
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.
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]).
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.
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.
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):
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| inVentiv Health Clinical Research Services LLC, a Syneos Health company (" Syneos Health ") | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35789594 | Derived | Kemper C, Benham D, Brothers S, Wahlestedt C, Volmar CH, Bennett D, Hayward M. Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM). AAPS Open. 2022;8(1):11. doi: 10.1186/s41120-022-00058-1. Epub 2022 Jun 30. |
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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 took part in the study at 1 investigative site in the United States from 21 January 2021 to 31 May 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | 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. |
| FG001 | Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | 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. |
| FG002 | Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | 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. |
| FG003 | Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 Study Period 1 |
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| ||||||||||||||||||
| Part 1 Study Period 2 |
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| Part 1 Study Period 3 |
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| Part 2 Study Period 4 |
|
The safety population was defined as all the participants who received at least one dose of the study medication. There were total of 21 participants who started the study as single arm in part 1: Study period 1 and same participants received treatment in the following periods. Only 3 additional participants were enrolled in Part 1, study period 3. Therefore, to avoid double counting of the participants, Baseline data was collected and reported as single arm for all 24 participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The safety population was defined as all participants who received at least one dose of the study medication. | Posted | Count of Participants | Participants | From first dose of study drug administration up to 131 days |
|
From first dose of study drug administration up to 131 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: JOTROL (Resveratrol) 200 mg (Treatment A) | Participants received JOTROL (resveratrol) 200 (2*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Wyatt | Marshall A. Hayward, Ph.D., Jupiter Orphan Therapeutics Inc. | 305-547-5857 | david.wyatt@syneoshealth.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 25, 2020 | May 30, 2022 | Prot_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 19, 2020 | May 30, 2022 | SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 17, 2020 | Dec 2, 2020 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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| 500 mg resveratrol as JOTROL | Drug | Second (intermediate) dose of single ascending dose study |
|
| 700 mg resveratrol as JOTROL | Drug | Third (highest) dose of single ascending dose study |
|
| 500 mg resveratrol as JOTROL administered to assess influence of food | Drug | 500 mg resveratrol as JOTROL administered to assess influence of food |
|
Cmax was the maximum observed plasma concentration obtained directly from the concentration versus time curve. |
| 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 |
| 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. | 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 (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. | 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 Rate Constant (Kel) for Resveratrol | Kel was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | 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 |
| 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. | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
| 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. | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
| Time of Rmax (Tmax) for Resveratrol | Tmax was the time after administration of a drug when the Rmax is reached. | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
| Renal Clearance (CLr) for Resveratrol | CLr was calculated as Ae0-t/AUC0-t (plasma) where t is Tlast. | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
| Withdrawal by Subject |
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| COMPLETED |
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| NOT COMPLETED |
|
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| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
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| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
Participants received JOTROL (resveratrol) 200 (2*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1. |
| OG001 | Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | 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 day washout period was maintained in study period 1 and 2. |
| OG002 | Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | 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 day washout period was maintained in study period 2 and 3. |
| OG003 | Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | 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 day washout period was maintained in study period 3 and 4. |
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage AUC | 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 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | hour | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1 per hour (1/h) | 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 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram (ng) | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per hour (ng/h) | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
|
|
|
| Secondary | Time of Rmax (Tmax) for Resveratrol | Tmax was the time after administration of a drug when the Rmax is reached. | 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. | Posted | Median | Full Range | hour | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
|
|
|
| Secondary | Renal Clearance (CLr) for Resveratrol | CLr was calculated as Ae0-t/AUC0-t (plasma) where t is Tlast. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1 |
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 7 |
| 21 |
| EG001 | Part 1: JOTROL (Resveratrol) 500 mg (Treatment B) | 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. | 0 | 16 | 0 | 16 | 4 | 16 |
| EG002 | Part 1: JOTROL (Resveratrol) 700 mg (Treatment C) | 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. | 0 | 18 | 0 | 18 | 6 | 18 |
| EG003 | Part 2: JOTROL (Resveratrol) 500 mg (Treatment D) | 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. | 0 | 15 | 0 | 15 | 6 | 15 |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| SARS-CoV-2 test positive | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| White blood cells urine | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |
|
| Resveratrol-3-Glucuronide |
|
|
| Resveratrol-3-Sulfate |
|
|
| Resveratrol-4'-Glucuronide |
|
|
| Resveratrol-3-Glucuronide |
|
| Resveratrol-3-Sulfate |
|
| Resveratrol-4'-Glucuronide |
|
| Resveratrol-3-Glucuronide |
|
| Resveratrol-3-Sulfate |
|
| Resveratrol-4'-Glucuronide |
|