Trial Outcomes & Findings for Pharmacokinetics of Centella Asiatica in the Elderly (NCT NCT03929250)

Last Updated: 2025-08-06

Results Overview

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 12 hour period, using high performance liquid chromatography tandem mass spectrometry in order to generate a pharmacokinetic curve, and determine pharmacokinetic parameters (maximum concentration and area under the curve) for each of the two doses (2g and 4g).

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

8 participants

Primary outcome timeframe

A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

Results posted on

2025-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	2g CAW Dose, Then 4g CAW Dose Participants first receive a single dose of product containing 2g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 4g CAW.	4g CAW Dose, Then 2g CAW Dose Participants first receive a single dose of product containing 4g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 2g CAW.
Overall Study STARTED	4	4
Overall Study COMPLETED	4	3
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	2g CAW Dose, Then 4g CAW Dose Participants first receive a single dose of product containing 2g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 4g CAW.	4g CAW Dose, Then 2g CAW Dose Participants first receive a single dose of product containing 4g CAW, then after a minimum washout period of 2 weeks, they receive a single dose of product containing 2g CAW.
Overall Study Blood draws could not be successfully obtained	0	1

Baseline Characteristics

Pharmacokinetics of Centella Asiatica in the Elderly

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=8 Participants All participants including those in the (a) 2g CAW, then 4g CAW arm or (b) 4g CAW then 2g CAW arm
Age, Continuous	71 years STANDARD_DEVIATION 5.5 • n=99 Participants
Sex: Female, Male Female	4 Participants n=99 Participants
Sex: Female, Male Male	4 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	8 participants n=99 Participants
Body mass index	28.5 kg/m^2 STANDARD_DEVIATION 1.5 • n=99 Participants
Systolic blood pressure	125 mmHg STANDARD_DEVIATION 4 • n=99 Participants
Diastolic blood pressure	78 mmHg STANDARD_DEVIATION 2 • n=99 Participants
Body temperature	98.3 degrees Fahrenheit STANDARD_DEVIATION 0.2 • n=99 Participants
Heart rate	67 beats per minute STANDARD_DEVIATION 4 • n=99 Participants
White blood cell	6.7 10^3 cells/cu mm STANDARD_DEVIATION 0.4 • n=99 Participants
Red blood cell	5.0 10^6 cells/cu mm STANDARD_DEVIATION 0.2 • n=99 Participants
Hemoglobin	15.3 g/dL STANDARD_DEVIATION 0.5 • n=99 Participants
Hematocrit	46.4 percentage STANDARD_DEVIATION 1.4 • n=99 Participants
Platelet	233.9 10^3 cells/cu mm STANDARD_DEVIATION 7.5 • n=99 Participants
Blood glucose	90.6 mg/dL STANDARD_DEVIATION 4.3 • n=99 Participants
Blood urea nitrogen	15.8 mg/dL STANDARD_DEVIATION 1 • n=99 Participants
Creatinine	0.7 mg/dL STANDARD_DEVIATION 0.6 • n=99 Participants
total bilirubin	0.5 mg/dL STANDARD_DEVIATION 0.03 • n=99 Participants
Aspartate aminotransferase	24.6 U/L STANDARD_DEVIATION 0.7 • n=99 Participants
Alanine aminotransferase	30.1 U/L STANDARD_DEVIATION 2.5 • n=99 Participants
Total protein	7.4 g/dL STANDARD_DEVIATION 0.1 • n=99 Participants
Albumin	4.0 g/dL STANDARD_DEVIATION 0.1 • n=99 Participants
Sodium	140.5 mmol/L STANDARD_DEVIATION 0.5 • n=99 Participants
Chloride	106.5 mmol/L STANDARD_DEVIATION 0.5 • n=99 Participants
Potassium	4.0 mmol/L STANDARD_DEVIATION 0.1 • n=99 Participants
Total CO2	28.9 mmol/L STANDARD_DEVIATION 0.5 • n=99 Participants
Calcium	9.2 mg/dL STANDARD_DEVIATION 0.1 • n=99 Participants
Anion gap	5.3 mEq/L STANDARD_DEVIATION 0.5 • n=99 Participants

PRIMARY outcome

Timeframe: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Asiatic acid	174 ng/mL Standard Error 22	372 ng/mL Standard Error 53
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Caffeic acid	0.3 ng/mL Standard Error 0.1	0.5 ng/mL Standard Error 0.1
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Dihydrocaffeic acid	0.4 ng/mL Standard Error 0.1	0.5 ng/mL Standard Error 0.1
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Dihydroferulic acid	9.3 ng/mL Standard Error 4.4	8.1 ng/mL Standard Error 2.9
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Dicaffeoylquinic acids	1.2 ng/mL Standard Error 0.6	1.9 ng/mL Standard Error 0.8
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Ferulic acid	1.5 ng/mL Standard Error 0.3	1.5 ng/mL Standard Error 0.6
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. 3-(3-hydroxyphenyl)propionic acid	5.8 ng/mL Standard Error 3.0	10.6 ng/mL Standard Error 2.9
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Isoferulic acid	1.5 ng/mL Standard Error 0.8	1.5 ng/mL Standard Error 0.4
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Madecassic acid	107 ng/mL Standard Error 18	197 ng/mL Standard Error 43
Maximum Human Plasma Concentration of Bioactives From Centella Asiatica. Monocaffeoylquinic acids	1.6 ng/mL Standard Error 0.5	4.2 ng/mL Standard Error 1.4

PRIMARY outcome

Timeframe: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Asiatic acid	48755 ng/mL*hr Standard Error 7152	91330 ng/mL*hr Standard Error 17723
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Caffeic acid	1.8 ng/mL*hr Standard Error 0.5	2.4 ng/mL*hr Standard Error 0.6
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Dihydrocaffeic acid	1.7 ng/mL*hr Standard Error 0.6	1.9 ng/mL*hr Standard Error 0.5
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Dihydroferulic acid	35.6 ng/mL*hr Standard Error 18.6	41.0 ng/mL*hr Standard Error 12.7
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Dicaffeoylquinic acids	3.4 ng/mL*hr Standard Error 1.8	5.0 ng/mL*hr Standard Error 1.5
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Ferulic acid	11.3 ng/mL*hr Standard Error 2.9	9.9 ng/mL*hr Standard Error 2.8
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. 3-(3-hydroxyphenyl)propionic acid	56.8 ng/mL*hr Standard Error 31.7	50.2 ng/mL*hr Standard Error 15.1
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Isoferulic acid	5.3 ng/mL*hr Standard Error 1.6	7.4 ng/mL*hr Standard Error 1.6
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Madecassic acid	26771 ng/mL*hr Standard Error 3585	48373 ng/mL*hr Standard Error 12476
Total Plasma Concentration Over Time (Area Under the Curve) From Centella Asiatica Water Extract Product. Monocaffeoylquinic acids	6.2 ng/mL*hr Standard Error 2.4	10.1 ng/mL*hr Standard Error 3.9

PRIMARY outcome

Timeframe: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

The half-life (t1/2) of the known bioactive compounds was calculated from the plasma concentrations measured by high performance liquid chromatography tandem mass spectrometry to help determine dosage intervals.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Half-life Asiatic acid	4.1 hours Standard Error 0.7	4.9 hours Standard Error 1.3
Half-life Caffeic acid	8.4 hours Standard Error 3	10.3 hours Standard Error 3.7
Half-life Dihydrocaffeic acid	1.8 hours Standard Error 1.2	1.9 hours Standard Error 0.8
Half-life Dihydroferulic acid	7.1 hours Standard Error 1.7	6.6 hours Standard Error 3.8
Half-life Dicaffeoylquinic acids	2 hours Standard Error 1.2	2.6 hours Standard Error 1.8
Half-life Ferulic acid	14.1 hours Standard Error 3.9	2.9 hours Standard Error 1.3
Half-life 3-(3-hydroxyphenyl)propionic acid	5 hours Standard Error 2	2.6 hours Standard Error 0.5
Half-life Isoferulic acid	7 hours Standard Error 2.4	3.5 hours Standard Error 0.5
Half-life Madecassic acid	9.2 hours Standard Error 3.7	6.7 hours Standard Error 0.8
Half-life Monocaffeoylquinic acids	3.4 hours Standard Error 1.1	1.7 hours Standard Error 1.1

PRIMARY outcome

Timeframe: A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes).

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

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Time of Maximum Concentration Asiatic acid	2.2 hours Standard Error 0.4	2.8 hours Standard Error 0.2
Time of Maximum Concentration Caffeic acid	5.3 hours Standard Error 1.9	4.5 hours Standard Error 1.6
Time of Maximum Concentration Dihydrocaffeic acid	6.1 hours Standard Error 1.7	3.2 hours Standard Error 1.3
Time of Maximum Concentration Dihydroferulic acid	5.9 hours Standard Error 1.6	5.7 hours Standard Error 1.5
Time of Maximum Concentration Dicaffeoylquinic acids	3.7 hours Standard Error 1.9	4.3 hours Standard Error 1.7
Time of Maximum Concentration Ferulic acid	5.9 hours Standard Error 1.3	7.1 hours Standard Error 1.2
Time of Maximum Concentration 3-(3-hydroxyphenyl)propionic acid	7.4 hours Standard Error 1.5	5.7 hours Standard Error 0.7
Time of Maximum Concentration Isoferulic acid	2.4 hours Standard Error 1	1 hours Standard Error 0.32
Time of Maximum Concentration Madecassic acid	2.4 hours Standard Error 0.3	2.7 hours Standard Error 0.2
Time of Maximum Concentration Monocaffeoylquinic acids	1.2 hours Standard Error 0.4	3.4 hours Standard Error 1.2

SECONDARY outcome

Timeframe: Over 12 hours post-administration

The concentration of bioactive compounds from Centella asiatica (triterpenes, caffeoylquinic acids, and their metabolites) will be measured in a pooled urine sample collected over 12 hours after CAP administration and analyzed using high performance liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Urinary Excretion Asiatic acid	0 micrograms Standard Error 0	0 micrograms Standard Error 0
Urinary Excretion Asiaticoside	20.7 micrograms Standard Error 6.7	18.6 micrograms Standard Error 4.5
Urinary Excretion Caffeic acid	42.8 micrograms Standard Error 11.6	48.7 micrograms Standard Error 9.3
Urinary Excretion Dihydrocaffeic acid	26.8 micrograms Standard Error 10	24.8 micrograms Standard Error 6.1
Urinary Excretion Dihydroferulic acid	225.5 micrograms Standard Error 83.5	225.1 micrograms Standard Error 94.8
Urinary Excretion Dicaffeoylquinic acids	0 micrograms Standard Error 0	0 micrograms Standard Error 0
Urinary Excretion Ferulic acid	146.8 micrograms Standard Error 33.5	137.4 micrograms Standard Error 24.6
Urinary Excretion 3-(3-hydroxyphenyl)propionic acid	223.4 micrograms Standard Error 76.7	247.9 micrograms Standard Error 73.6
Urinary Excretion Isoferulic acid	65.9 micrograms Standard Error 23.1	225.1 micrograms Standard Error 15.9
Urinary Excretion Madecassic acid	0 micrograms Standard Error 0	0 micrograms Standard Error 0
Urinary Excretion Madecassoside	0 micrograms Standard Error 0	0 micrograms Standard Error 0
Urinary Excretion Monocaffeoylquinic acids	21.3 micrograms Standard Error 8.6	19.3 micrograms Standard Error 2.6

SECONDARY outcome

Timeframe: 720 minutes after administration

Oral temperature will be measured in degrees Fahrenheit by means of a thermometer.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Oral Temperature	98.2 degrees Fahrenheit Standard Error 0.1	98.1 degrees Fahrenheit Standard Error 0.1

SECONDARY outcome

Timeframe: 720 minutes after administration

Pulse rate will be measured peripherally over one minute.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Pulse Rate	69 beats per minute Standard Error 4	64 beats per minute Standard Error 3

SECONDARY outcome

Timeframe: 720 minutes after administration

Seated blood pressure will be measured in millimeters mercury.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Seated Systolic Blood Pressure	125 mmHg Standard Error 4	119 mmHg Standard Error 5

SECONDARY outcome

Timeframe: 720 minutes after administration

Height in centimeters and weight in kilograms will be measured and aggregated to measure body mass index in kilograms per meter squared (kg/m2).

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Body Mass Index	28.4 kg/m^2 Standard Error 1.3	28 kg/m^2 Standard Error 1.4

SECONDARY outcome

Timeframe: 0, 360 and 720 minutes after administration

Resting electrocardiography will be measured for up to five minutes using a five lead mobile electrocardiogram. The investigators will determine the number of participants who develop changes in electrocardiography compared to the zero minute timepoint following CAP administration.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Participants With Change in Electrocardiography	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 720 minutes after administration

Seated blood pressure will be measured in millimeters mercury.

Outcome measures

Outcome measures
Measure	2g CAW Dose n=7 Participants 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 Participants 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
Seated Diastolic Blood Pressure	74 mmHg Standard Error 3	69 mmHg Standard Error 1

Adverse Events

2g CAW Dose

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

4g CAW Dose

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Amala Soumyanath

Oregon Health & Science University

Phone: 503-494-6878

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	2g CAW Dose n=8 participants at risk 2g of Centella asiatica water extract in a standardized product. 2g Centella asiatica water extract product: 2g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.	4g CAW Dose n=8 participants at risk 4g of Centella asiatica water extract in a standardized product. 4g Centella asiatica water extract product: 4g Centella asiatica water extract product is a powder containing Centella asiatica water extract and excipients to improve palatability, color matching and dispersability in water. It will be consumed on an empty stomach orally suspended in 10-12 ounces of water.
General disorders Excessive sleep	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Psychiatric disorders Disappointment	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Psychiatric disorders Anxiety	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Social circumstances Boredom	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
General disorders Weakness/fatigue	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain or stiffness	37.5% 3/8 • Number of events 3 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Nervous system disorders Tremor	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Nervous system disorders Headache	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	25.0% 2/8 • Number of events 2 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Ear and labyrinth disorders Vertigo	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Ear and labyrinth disorders Tinnitus	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Eye disorders Blurred vision	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Cardiac disorders Hypotension	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Cardiac disorders Fainting/dizziness	37.5% 3/8 • Number of events 3 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Respiratory, thoracic and mediastinal disorders Coughing	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Vascular disorders Peripheral edema or swelling	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Diarrhea	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Gas/indigestion	25.0% 2/8 • Number of events 2 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Constipation	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Increased thirst	25.0% 2/8 • Number of events 2 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Dry throat	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Dry mouth	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Abnormal or metallic taste in mouth	25.0% 2/8 • Number of events 2 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	50.0% 4/8 • Number of events 4 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Abdominal pain/cramps	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Decreased appetite	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Nausea	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Gastrointestinal disorders Belching	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Renal and urinary disorders Increased urination	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Renal and urinary disorders Urine color change	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	25.0% 2/8 • Number of events 2 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Itchiness/dryness	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Skin color change	37.5% 3/8 • Number of events 3 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Redness	50.0% 4/8 • Number of events 4 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Rash/hives	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Bruising	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Skin puffiness/ tissue fluid	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
Skin and subcutaneous tissue disorders Ecchymosis, indurate	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
General disorders Weight gain	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.
General disorders Weight loss	12.5% 1/8 • Number of events 1 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.	0.00% 0/8 • 0, 6, 12 and 24 hours after administration of each dose level (2g CAW or 4g CAW) A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events.