Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R61AT009628 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Participant study visits not possible during COVID-19 pandemic. Funder not able to support a continuation at some future date.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
Not provided
Not provided
Not provided
Not provided
This study will measure the oral bioavailability and pharmacokinetics of known bioactive compounds from a standardized Centella asiatica water extract product (CAP) in mildly demented elders on cholinesterase inhibitor therapy. Compound levels will be measured in human plasma and urine over 10 hours after acute oral administration of two doses of the botanical extract product. The dose giving maximum plasma levels (Cmax)closest to those observed in the investigator's mouse studies, the area under the curve (AUC0-12), as well as the rate of clearance (t ½) of the known compounds and time of maximum concentration (tmax), will be identified. These data will be used to inform decisions on the dosage and dosing frequency for future clinical trials.
PRIMARY OBJECTIVES:
OUTLINE:
Participants will orally consume a single administration of a standardized Centella asiatica water extract product (CAP). Two doses (2g and 4g CAW) will be administered on separate occasions, at least two weeks apart. The levels of known bioactive compounds present in Centella asiatica will be measured in human plasma and urine over 10 hours after administration of each of the doses.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2g CAP | Experimental | Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
|
| 4g CAP | Experimental | Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2g Centella asiatica water extract product | Drug | 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax) | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration) for each of the two doses (2g and 4g). | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes). |
| Time of Maximum Concentration (Tmax) | The time of maximum concentration (Tmax) of the known bioactive compounds and their metabolites will be calculated from the concentrations measured by high performance liquid chromatography tandem mass spectrometry in order to help determine dosage intervals | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480 and 600 minutes). |
| Half-life (t1/2) | The half-life (t1/2) of the known bioactive compounds and their metabolites will be calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals. | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480, and 600 minutes). |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) of the Concentration vs Time Profiles of Known Bioactives From Centella Asiatica | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (area under the curve) for each of the two doses (2g and 4g). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Amala Soumyanath, PhD | OHSU Department of Neurology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health and Science University Department of Neurology | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35096945 | Background | Wright KM, McFerrin J, Alcazar Magana A, Roberts J, Caruso M, Kretzschmar D, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges. Front Nutr. 2022 Jan 14;8:799137. doi: 10.3389/fnut.2021.799137. eCollection 2021. | |
| 35204098 | Result | Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcazar Magana A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial. Antioxidants (Basel). 2022 Jan 23;11(2):215. doi: 10.3390/antiox11020215. |
Not provided
Not provided
ALL IPD that underlie results in a publication will be shared via a published journal article.
Immediately after publication and for a period of 3 years following publication.
Anyone who wishes access to the data, for any reason. Requests should be directed to Dr. Amala Soumyanath at soumyana@ohsu.edu
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: 2g CAP Then 4g CAP | Participants first received one single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. After a washout period of 14 days, they then received one single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
| FG001 | Experimental: 4g CAP Then 2g CAP | Participants first received one single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. After a washout period of 14 days, they then received one single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Baseline values for all participants before randomization |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Peak Plasma Concentration of Centella Asiatica Bioactive Compounds (Cmax) | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration) for each of the two doses (2g and 4g). | The pharmacokinetic parameter (Cmax) and time curves was calculated using non-compartmental analysis of plasma concentration versus time data using Excel software PK-solver (version 2.0). | Posted | Mean | Standard Error | ng/mL | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, and 600 minutes). |
|
Adverse events were collected during each study visit, 24 hours following study drug administration at each study visit, and 7 days after study visit two (end of study).
Vital signs, EKG and CMP were monitored at baseline and during the visit. Adverse events were collected using a multi-system adverse events questionnaire during and after the visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2g CAP | Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | Systematic Assessment |
Study was discontinued before the target number of participants were enrolled due to pandemic-related restrictions.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Amala Soumyanath | Oregon Health & Science University | 503-494-6878 | soumyana@ohsu.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 1, 2020 | Apr 8, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
This is an outpatient open-label clinical study using a blinded randomized crossover design of two doses.
Not provided
Not provided
Randomization will use an arm equivalence design to promote equal numbers of participants for each order schema. All participants will be blinded to the dose they will be receiving at each visit. The investigators have developed a formulation that tastes and looks very similar at each dose. The investigator administering the intervention and the analyst performing the liquid chromatography analysis of collected plasma will be blinded as to the dose of the product administered. The liquid chromatography analyst will also be blinded as to the time point of collection.
|
|
| 4g Centella asiatica water extract product | Drug | 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
|
|
| A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480 and 600 minutes). |
| Total Urinary Excretion | All urine produced over the 10 hours post-administration was collected into a single container. The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) was measured in the single total urine sample collected over 10 hours after CAP administration. Urine samples were treated with glucuronidase and sulfatase enzymes to release analyte from conjugated (Phase II metabolite) forms of the analyte. All samples were analyzed using high performance liquid chromatography tandem mass spectrometry. The concentrations obtained were multiplied by total urine volume to obtain the total amount of that analyte excreted. The total amount (free and conjugated forms) in micrograms of of each analyte in the 10h urine sample is reported. | Total 10 hours |
| NRF2 Expression | NRF2 gene expression was measured in peripheral blood mononuclear cells following consumption of 2g and 4g of Centella asiatica water extract product (CAP). | 0, 1, 2, 3, 4, and 6h following study intervention |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| White blood cells | Mean | Standard Deviation | x10^3 cells/uL |
|
| Systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Body temperature | Mean | Standard Deviation | Celsius |
|
| Heart rate | Mean | Standard Deviation | beats per minute |
|
| Red blood cells | Mean | Standard Deviation | x10^6 cells/uL |
|
| Hemoglobin | Mean | Standard Deviation | g/dL |
|
| Hematocrit | Mean | Standard Deviation | percentage |
|
| Platelets | Mean | Standard Deviation | x10^3 platelets/uL |
|
| Blood glucose | Mean | Standard Deviation | mg/dL |
|
| Blood urea nitrogen | Mean | Standard Deviation | mg/dL |
|
| Creatinine | Mean | Standard Deviation | mg/dL |
|
| Total bilirubin | Mean | Standard Deviation | mg/dL |
|
| Aspartate aminotransferase | Mean | Standard Deviation | U/L |
|
| Alanine aminotransferase | Mean | Standard Deviation | U/L |
|
| Alkaline phosphatase | Mean | Standard Deviation | U/L |
|
| Total protein | Mean | Standard Deviation | g/dL |
|
| Albumin | Mean | Standard Deviation | g/dL |
|
| Sodium | Mean | Standard Deviation | mmol/L |
|
| Chloride | Mean | Standard Deviation | mmol/L |
|
| Total CO^2 | Mean | Standard Deviation | mmol/L |
|
| Potassium | Mean | Standard Deviation | mmol/L |
|
| Calcium | Mean | Standard Deviation | mg/dL |
|
| Anion gap | Mean | Standard Deviation | mEq/L |
|
Single administration of 2g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
2g Centella asiatica water extract product: 2g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach.
| OG001 | 4g CAP | Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. 4g Centella asiatica water extract product: 4g of Centella asiatica water extract (CAW) in a standardized product containing excipients to improve palatability, color matching and dispersability. The product (CAP) is a powder which will be dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. |
|
|
|
| Primary | Time of Maximum Concentration (Tmax) | The time of maximum concentration (Tmax) of the known bioactive compounds and their metabolites will be calculated from the concentrations measured by high performance liquid chromatography tandem mass spectrometry in order to help determine dosage intervals | Posted | Mean | Standard Error | hours | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480 and 600 minutes). |
|
|
|
|
| Primary | Half-life (t1/2) | The half-life (t1/2) of the known bioactive compounds and their metabolites will be calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals. | Posted | Mean | Standard Error | hours | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480, and 600 minutes). |
|
|
|
|
| Secondary | Area Under the Curve (AUC) of the Concentration vs Time Profiles of Known Bioactives From Centella Asiatica | Following oral administration of a product made from a water extract of Centella asiatica (CAP), the plasma concentration of Centella asiatica derived bioactive compounds (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in blood samples obtained over a 10 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (area under the curve) for each of the two doses (2g and 4g). | Posted | Mean | Standard Error | ng x h/mL | A 10-hour post-administration period (15, 30, 45, 60, 90, 120, 150,180, 240, 360, 480 and 600 minutes). |
|
|
|
|
| Secondary | Total Urinary Excretion | All urine produced over the 10 hours post-administration was collected into a single container. The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) was measured in the single total urine sample collected over 10 hours after CAP administration. Urine samples were treated with glucuronidase and sulfatase enzymes to release analyte from conjugated (Phase II metabolite) forms of the analyte. All samples were analyzed using high performance liquid chromatography tandem mass spectrometry. The concentrations obtained were multiplied by total urine volume to obtain the total amount of that analyte excreted. The total amount (free and conjugated forms) in micrograms of of each analyte in the 10h urine sample is reported. | Posted | Mean | Standard Error | micrograms | Total 10 hours |
|
|
|
|
| Secondary | NRF2 Expression | NRF2 gene expression was measured in peripheral blood mononuclear cells following consumption of 2g and 4g of Centella asiatica water extract product (CAP). | Posted | Mean | Standard Error | fold change in expression from time 0h | 0, 1, 2, 3, 4, and 6h following study intervention |
|
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | 4g CAP | Single administration of 4g of Centella asiatica water extract standardized product dissolved in 10-12 ounce of water and consumed by mouth once on an empty stomach. | 0 | 4 | 0 | 4 | 4 | 4 |
| Drowsiness | Psychiatric disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Inability to sit still | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Rigidity of any body part | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Blurred vision | Eye disorders | Systematic Assessment |
|
| Sore throat | Gastrointestinal disorders | Systematic Assessment |
|
| Allergy symptoms | Immune system disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Heart racing or irregular beating | Cardiac disorders | Systematic Assessment |
|
| Hypertension/elevated blood pressure | Cardiac disorders | Systematic Assessment |
|
| Increased appetite | Gastrointestinal disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Increased urination | Renal and urinary disorders | Systematic Assessment |
|
| Sunburn or sensitivity of skin to light | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Generalized pain | General disorders | Systematic Assessment |
|
Not provided
Not provided
| Dihydrocaffeic acid |
|
| Dihydroferulic acid |
|
| Dicaffeoylquinic acids |
|
| Ferulic acid |
|
| 3-(3-hydroxyphenyl)propionic acid |
|
| Isoferulic acid |
|
| Madecassic acid |
|
| Monocaffeoylquinic acids |
|
Caffeic acid
| t-test, 2 sided |
| 0.40 |
| Equivalence |
Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydrocaffeic acid | t-test, 2 sided | 0.20 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydroferulic acid | t-test, 2 sided | 0.48 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Ferulic acid | t-test, 2 sided | 0.20 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 3-(3-hydroxyphenyl)propionic acid | t-test, 2 sided | 0.32 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Isoferulic acid | t-test, 2 sided | 0.35 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Madecassic acid | t-test, 2 sided | 0.52 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Monocaffeoylquinic acids | t-test, 2 sided | 0.13 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydrocaffeic acid |
|
| Dihydroferulic acid |
|
| Dicaffeoylquinic acids |
|
| Ferulic acid |
|
| 3-(3-hydroxyphenyl)propionic acid |
|
| Isoferulic acid |
|
| Madecassic acid |
|
| Monocaffeoylquinic acids |
|
Dihydrocaffeic acid
| t-test, 2 sided |
| 0.08 |
| Equivalence |
Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydroferulic acid | t-test, 2 sided | 0.23 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Ferulic acid | t-test, 2 sided | 0.14 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 3-(3-hydroxyphenyl)propionic acid | t-test, 2 sided | 0.28 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Isoferulic acid | t-test, 2 sided | 0.17 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Madecassic acid | t-test, 2 sided | 0.98 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Monocaffeoylquinic acids | t-test, 2 sided | 0.16 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydrocaffeic acid |
|
| Dihydroferulic acid |
|
| Dicaffeoylquinic acids |
|
| Ferulic acid |
|
| 3-(3-hydroxyphenyl)propionic acid |
|
| Isoferulic acid |
|
| Madecassic acid |
|
| Monocaffeoylquinic acids |
|
Caffeic acid
| t-test, 2 sided |
| 0.01 |
| Equivalence |
Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydrocaffeic acid | t-test, 2 sided | 0.06 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydroferulic acid | t-test, 2 sided | 0.08 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dicaffeoylquinic acids | t-test, 2 sided | 0.56 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Ferulic acid | t-test, 2 sided | 0.21 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 3-(3-hydroxyphenyl)propionic acid | t-test, 2 sided | 0.05 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Isoferulic acid | t-test, 2 sided | 0.05 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Madecassic acid | t-test, 2 sided | 0.23 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Monocaffeoylquinic acids | t-test, 2 sided | 0.16 | Equivalence | Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydroferulic acid |
|
| Ferulic acid |
|
| 3-(3-hydroxyphenyl)propionic acid |
|
| Isoferulic acid |
|
| Madecassic acid |
|
| Monodicaffeoylquinic acids |
|
| Madecassoside |
|
Madecassic acid
| t-test, 2 sided |
| 0.09 |
| Equivalence |
Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Asiaticoside | t-test, 2 sided | 0.4 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Madecassoside | t-test, 2 sided | 0.6 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Monocaffeoylquinic acids | t-test, 2 sided | 0.4 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dicaffeoylquinic acids | t-test, 2 sided | 0.1 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 3-(3-hydroxyphenyl)propionic acid | t-test, 2 sided | 0.9 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Caffeic acid | t-test, 2 sided | 0.03 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Ferulic acid | t-test, 2 sided | 0.9 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Isoferulic acid | t-test, 2 sided | 0.6 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydroferulic acid | t-test, 2 sided | 0.4 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| Dihydrocaffeic acid | t-test, 2 sided | 0.8 | Equivalence | Two-sided paired t-tests were used to compare the ng/mL between the 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 2 h |
|
| 3 h |
|
| 4 h |
|
| 6 h |
|
| t-test, 1 sided |
| 0.1 |
| Equivalence |
Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 3 hours | t-test, 1 sided | 0.3 | Equivalence | Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 4 hours | t-test, 1 sided | 0.5 | Equivalence | Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |
| 6 hours | t-test, 1 sided | 0.5 | Equivalence | Two-sided paired t-tests were used to compare fold induction between 2g and 4g doses. A p-value of less than 0.05 was considered statistically significant. |