Drug Use
Conditions
Keywords
bioequivalence, pharmacokinetics, Indonesian healthy subject, Acyclovir
Brief summary
The objective of this present study was to asses the pharmacokinetic properties of acyclovir tablet from new product formulation (PT. Kimia Farma (Persero) Tbk) to its innovator product, Zovirax® tablet (Glaxo Wellcome S.A., Aranda, Spain)
Detailed description
Twenty-eight healty subjects were given a single dose of acyclovir tablet or Zovirax® in dosage form 200 mg and 400mg with 240 mL of water. Then the blood samples for acyclovir was drawn and analyzed using LCMS/MS. All subjects sample plasma were analyzed for pharmacokinetic evaluation
Interventions
DRUGAcyclovir 200 MG
Administered with 240 mL of water
DRUGAcyclovir 400 MG
Administered with 240 mL of water
DRUGZovirax 200 MG Tablet
Administered with 240 mL of water
DRUGZovirax 400 MG Tablet
Administered with 240 mL of water
Sponsors
PT Pharma Metric Labs
PT. Kimia Farma (Persero) Tbk
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, single blind, single dose, 2-periods, cross-over design study with one week washout period between each treatment in 28 healthy subjects under fasting condition
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* body weight within normal range (body mass index between 18 and 25 kg/m2) * had normal blood pressure (systolic was ranged between 90 to 120 mmHg and diastolic was ranged between 60 to 80 mmHg) * had normal electrocardiogram * absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening
Exclusion criteria
* pregnant women * nursing mothers * women of childbearing potential without adequate contraception * had a history of contraindication or hypersensitivity to aciclovir, or other antiviral or other ingredients in the study products or a history of serious allergic reaction to any drug, * a significant allergic disease, or allergic reaction; presence of medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease * presence of any coagulation disorder or clinically significant hematology abnormalities; using any medication (prescription or non-prescription drug, food supplement, herbal medicine) * particularly the medication known to affect the pharmacokinetics of the study drug * who had participated in any clinical study within 3 months prior to the study (\< 90 days) * subjects who had donated or lost 300 ml (or more) of blood within 3 months prior to the study * who were positive to HIV, HBsAg, and HCV tests * who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits * poor venous access; and who smoked more than 10 cigarettes a day * had a history of drug or alcohol abuse within 12 months prior to screening for this study and who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter | before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing | Maximum plasma concentration (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio | before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing | The ratio between maximum concentration of test drug and reference drug after drug administration |
Countries
Indonesia
Participant flow
Pre-assignment details
The study was conducted with two types of drug doses, which were dose of 200 mg and 400 mg. Of each dose performed on 28 subjects
Participants by arm
| Arm | Count |
|---|---|
| Total Number of Participants for Dose 200 mg All participants received Acyclovir Tablet 200 mg with 240 mL of water (new and marketed) | 28 |
| Total Number of Participants for Dose 400 mg All participants received Acyclovir Tablet 400 mg with 240 mL of water (new and marketed) | 28 |
| Total | 56 |
Baseline characteristics
| Characteristic | Total Number of Participants for Dose 200 mg | Total Number of Participants for Dose 400 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 28 Participants | 56 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 18 Participants | 21 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 1 / 26 | 1 / 26 | 1 / 28 | 1 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Pharmacokinetics Parameter
Maximum plasma concentration (Cmax)
Time frame: before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acyclovir 200 mg Tablet | Pharmacokinetics Parameter | 613.21 ng/mL | Standard Deviation 244.06 |
| Zovirax® 200 mg Tablet | Pharmacokinetics Parameter | 675.58 ng/mL | Standard Deviation 258.18 |
| Acyclovir 400 mg Tablet | Pharmacokinetics Parameter | 807.13 ng/mL | Standard Deviation 278.85 |
| Zovirax® 400 mg Tablet | Pharmacokinetics Parameter | 882.89 ng/mL | Standard Deviation 351.97 |
Primary
Pharmacokinetics Parameter
Area Under Curve from 0 to 24 hours (AUCt)
Time frame: Predose at (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acyclovir 200 mg Tablet | Pharmacokinetics Parameter | 3609.80 ng*h/mL | Standard Deviation 1425.19 |
| Zovirax® 200 mg Tablet | Pharmacokinetics Parameter | 3865.20 ng*h/mL | Standard Deviation 1339.05 |
| Acyclovir 400 mg Tablet | Pharmacokinetics Parameter | 4583.29 ng*h/mL | Standard Deviation 1518.93 |
| Zovirax® 400 mg Tablet | Pharmacokinetics Parameter | 5088.28 ng*h/mL | Standard Deviation 1758.74 |
Secondary
Geometric Mean Ratio
The ratio between maximum concentration of test drug and reference drug after drug administration
Time frame: before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Acyclovir 200 mg Tablet | Geometric Mean Ratio | 90.65 percentage |
| Zovirax® 200 mg Tablet | Geometric Mean Ratio | 90.65 percentage |
| Acyclovir 400 mg Tablet | Geometric Mean Ratio | 93.63 percentage |
| Zovirax® 400 mg Tablet | Geometric Mean Ratio | 93.63 percentage |
Secondary
Geometric Mean Ratio
The ratio between area under curve from 0 to 24 hours of test drug and reference drug
Time frame: before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Acyclovir 200 mg Tablet | Geometric Mean Ratio | 92.74 percentage |
| Zovirax® 200 mg Tablet | Geometric Mean Ratio | 92.74 percentage |
| Acyclovir 400 mg Tablet | Geometric Mean Ratio | 90.10 percentage |
| Zovirax® 400 mg Tablet | Geometric Mean Ratio | 90.10 percentage |