Drug Use
Conditions
Keywords
cyproterone acetate, ethinyl estradiol, bioequivalence, cross-over design study, pharmacokinetics, Indonesian healthy female
Brief summary
The study was conducted to investigate whether 2 mg cyproterone acetate (CPA) and 0.035 mg ethinyl estradiol (EE) film-coated tablet (Elzsa®) manufactured by PT. Sydna Farma was bioequivalent to its reference product, Diane®-35 sugar-coated tablet manufactured by Bayer Weimar GmbH, Germany, imported by PT. Bayer Indonesia, Depok, Indonesia.
Detailed description
Twenty four healty female subjects were given a single dose of Elzsa® FCT or or Diane®-35 with 240 mL of water. Then the blood samples for CPA and EE were drawn and analyzed using LCMS/MS. All subjects sample plasma were analyzed for pharmacokinetic evaluation
Interventions
DRUGElzsa film-coated tablet
Administered with 240 mL of water
DRUGDiane-35 Sugar-coated tablet
Administered with 240 mL of water
Sponsors
PT Pharma Metric Labs
PT Sydna Farma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.
Eligibility
Sex/Gender
FEMALE
Age
19 Years to 54 Years
Healthy volunteers
Yes
Inclusion criteria
The inclusion criteria are healthy female subjects who/with: * have read the subject information and signed informed consent documents * age 18 - 55 years * body mass index between 18-25 kg/m2 * have a normal electrocardiogram * blood pressure within normal range (90-120 mmHg for systolic blood pressure and 60-80 mmHg for diastolic blood pressure) * heart rate within normal range (60-100 bpm) * with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening * pass hormone screening related to cyproterone acetate and ethinyl estradiol
Exclusion criteria
Any of the following criteria will exclude the subject from the study: * those who are pregnant and/or nursing woman. * those with history of hypersensitivity to cyproterone acetate and ethinyl estradiol or other oral contraception or other ingredients in the drugs or a history of serious allergic reaction to any drug, significant allergic disease, allergic reaction, or active allergic. * those with a history or presence medical condition which might significantly influence the pharmacokinetic of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease. * those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities, thrombophlebitis, and thromboembolic disorder. * those who are using any medication (prescription or non-prescription drug, food supplement, herbal medicine, oral contraception, anti-platelet drug), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day. * those who have participated in any clinical study within 3 months prior to the study (\< 90 days). * those who have donated or lost 300 ml (or more) of blood within 3 months prior to the study. * those who smoke. * those who are positive to HIV, HBsAg, and HCV tests (to be kept confidential). * those with a history of drug or alcohol abuse within 12 months prior to screening for this study. * those who are 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 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 15, 24, 36, 48 and 72 hours after dosing | Maximum plasma concentration (Cmax) |
Countries
Indonesia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Total Number of Participants All participants received 2 mg cyproterone acetate + 0.035 mg ethinylestradiol tablet (new and marketed) | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total Number of Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 24 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 24 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 6 / 24 | 9 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics Parameter
Maximum plasma concentration (Cmax)
Time frame: before dosing (0 h) and at 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 15, 24, 36, 48 and 72 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elzsa Film-coated Tablet | Pharmacokinetics Parameter | Cmax of Ethinyl Estradiol | 103.69 pg/mL | Standard Deviation 47.42 |
| Elzsa Film-coated Tablet | Pharmacokinetics Parameter | Cmax of Cyproterone Acetate | 17.39 pg/mL | Standard Deviation 13.77 |
| Diane-35 Sugar-coated Tablet | Pharmacokinetics Parameter | Cmax of Cyproterone Acetate | 16.20 pg/mL | Standard Deviation 13.81 |
| Diane-35 Sugar-coated Tablet | Pharmacokinetics Parameter | Cmax of Ethinyl Estradiol | 93.61 pg/mL | Standard Deviation 47.16 |
Primary
Pharmacokinetics Parameter
Area Under Curve from 0 to 72 hours (AUCt)
Time frame: before dosing (0 h) and at 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 15, 24, 36, 48 and 72 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elzsa Film-coated Tablet | Pharmacokinetics Parameter | AUC0-t of Cyproterone Acetate | 132.56 pg*hr/mL | Standard Deviation 73.19 |
| Elzsa Film-coated Tablet | Pharmacokinetics Parameter | AUC0-t of Ethinyl Estradiol | 870.45 pg*hr/mL | Standard Deviation 383.56 |
| Diane-35 Sugar-coated Tablet | Pharmacokinetics Parameter | AUC0-t of Cyproterone Acetate | 127.54 pg*hr/mL | Standard Deviation 89.41 |
| Diane-35 Sugar-coated Tablet | Pharmacokinetics Parameter | AUC0-t of Ethinyl Estradiol | 842.56 pg*hr/mL | Standard Deviation 398.66 |