Clinical trial NCT04964193: Bioequivalence Study of Cyproterone Acetate and Ethinyl Estradiol in Healthy Female Volunteers
Official title: Bioequivalence Study of 2 mg Cyproterone Acetate and 0.035 mg Ethinyl Estradiol in Indonesian Healthy Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Drug Use
Keywords: cyproterone acetate
ethinyl estradiol
bioequivalence
cross-over design study
pharmacokinetics
Indonesian healthy female
Lead sponsor: PT Sydna Farma
Sponsor class: INDUSTRY
Collaborators: name: PT Pharma Metric Labs
First posted: 2021-07-16
Enrollment: 24
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics Parameter
timeFrame: 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
measure: Pharmacokinetics Parameter
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Multiple Locations
country: Indonesia
facility: PT Pharma Metric Labs
state: Jakarta
Study officials:
References:
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citation: Speck U, Wendt H, Schulze PE, Jentsch D. Bio-availability and pharmacokinetics of cyproterone acetate-14C and ethinyloestradiol-3H after oral administration as a coated tablet (SH B 209 AB). Contraception. 1976 Aug;14(2):151-63. doi: 10.1016/0010-7824(76)90083-4.
citation: Kuhnz W, Staks T, Jutting G. Pharmacokinetics of cyproterone acetate and ethinylestradiol in 15 women who received a combination oral contraceptive during three treatment cycles. Contraception. 1993 Dec;48(6):557-75. doi: 10.1016/0010-7824(93)90118-q.
citation: Sedgwick P. Bias in randomised controlled trials: comparison of crossover group and parallel group designs. BMJ. 2015 Aug 7;351:h4283. doi: 10.1136/bmj.h4283. No abstract available.
citation: Garcia R, Benet M, Arnau C, Cobo E. Efficiency of the cross-over design: an empirical estimation. Stat Med. 2004 Dec 30;23(24):3773-80. doi: 10.1002/sim.2072.
citation: Sedgwick P. What is a crossover trial? BMJ. 2014 May 9;348:g3191. doi: 10.1136/bmj.g3191. No abstract available.
citation: Sedgwick P. Randomised controlled trials: "within subject" versus "between subject" designs. BMJ. 2014 Oct 24;349:g6435. doi: 10.1136/bmj.g6435. No abstract available.