Bioequivalence Study of Cyproterone Acetate and Ethinyl Estradiol in Healthy Female Volunteers

NCT ID: NCT04964193

Last Updated: 2022-01-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-12

Study Completion Date

2019-09-26

Brief Summary

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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

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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

Conditions

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Drug Use

Keywords

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cyproterone acetate ethinyl estradiol bioequivalence cross-over design study pharmacokinetics Indonesian healthy female

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Elzsa film-coated tablet

Participants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water

Group Type EXPERIMENTAL

Elzsa film-coated tablet

Intervention Type DRUG

Administered with 240 mL of water

Diane-35 Sugar-coated tablet

Participants received Diane-35 Sugar-coated tablet ( 2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water

Group Type ACTIVE_COMPARATOR

Diane-35 Sugar-coated tablet

Intervention Type DRUG

Administered with 240 mL of water

Interventions

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Elzsa film-coated tablet

Administered with 240 mL of water

Intervention Type DRUG

Diane-35 Sugar-coated tablet

Administered with 240 mL of water

Intervention Type DRUG

Other Intervention Names

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2 mg cyproterone acetate + 0.035 mg ethinylestradiol 2 mg cyproterone acetate + 0.035 mg ethinylestradiol

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

19 Years

Maximum Eligible Age

54 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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PT Pharma Metric Labs

INDUSTRY

Sponsor Role collaborator

PT Sydna Farma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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PT Pharma Metric Labs

Multiple Locations, Jakarta Special Capital Region, Indonesia

Site Status

Countries

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Indonesia

References

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Luque-Ramirez M, Alvarez-Blasco F, Botella-Carretero JI, Martinez-Bermejo E, Lasuncion MA, Escobar-Morreale HF. Comparison of ethinyl-estradiol plus cyproterone acetate versus metformin effects on classic metabolic cardiovascular risk factors in women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Jul;92(7):2453-61. doi: 10.1210/jc.2007-0282. Epub 2007 Apr 10.

Reference Type RESULT
PMID: 17426085 (View on PubMed)

Bhattacharya SM, Jha A. Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome. Fertil Steril. 2012 Oct;98(4):1053-9. doi: 10.1016/j.fertnstert.2012.06.035. Epub 2012 Jul 13.

Reference Type RESULT
PMID: 22795636 (View on PubMed)

Elger W, Beier S, Pollow K, Garfield R, Shi SQ, Hillisch A. Conception and pharmacodynamic profile of drospirenone. Steroids. 2003 Nov;68(10-13):891-905. doi: 10.1016/j.steroids.2003.08.008.

Reference Type RESULT
PMID: 14667981 (View on PubMed)

Bitzer J, Romer T, Lopes da Silva Filho A. The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review. Eur J Contracept Reprod Health Care. 2017 Jun;22(3):172-182. doi: 10.1080/13625187.2017.1317339. Epub 2017 Apr 27.

Reference Type RESULT
PMID: 28447864 (View on PubMed)

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.

Reference Type RESULT
PMID: 949892 (View on PubMed)

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.

Reference Type RESULT
PMID: 8131397 (View on PubMed)

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.

Reference Type RESULT
PMID: 26253465 (View on PubMed)

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.

Reference Type RESULT
PMID: 15580599 (View on PubMed)

Sedgwick P. What is a crossover trial? BMJ. 2014 May 9;348:g3191. doi: 10.1136/bmj.g3191. No abstract available.

Reference Type RESULT
PMID: 25134118 (View on PubMed)

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.

Reference Type RESULT
PMID: 25954990 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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440/STD/PML/2018

Identifier Type: -

Identifier Source: org_study_id