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

Drug Use Clinical Trial

Official title:

Bioequivalence Study of 2 mg Cyproterone Acetate and 0.035 mg Ethinyl Estradiol in Indonesian Healthy Females

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04964193
• Other study ID #: 440/STD/PML/2018
• Status: Completed
• Phase: N/A
• Start date: March 12, 2019
• Est. completion date: September 26, 2019

Study information

• Verified date: January 2022
• Source: PT Sydna Farma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 26, 2019
• Est. primary completion date: July 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years to 54 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Use

Intervention

Drug:
• Elzsa film-coated tablet
Administered with 240 mL of water
• Diane-35 Sugar-coated tablet
Administered with 240 mL of water

Locations

Country	Name	City	State
Indonesia	PT Pharma Metric Labs	Multiple Locations	Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
PT Sydna Farma	PT Pharma Metric Labs

Country where clinical trial is conducted

Indonesia, 

References & Publications (10)

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 — View Citation

Bitzer J, Römer 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. Rev — View Citation

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. — View 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. — View Citation

Kuhnz W, Staks T, Jütting 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. — View Citation

Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Martínez-Bermejo E, Lasunción MA, Escobar-Morreale HF. Comparison of ethinyl-estradiol plus cyproterone acetate versus metformin effects on classic metabolic cardiovascular risk factors in women wit — View 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. — View Citation

Sedgwick P. Randomised controlled trials: "within subject" versus "between subject" designs. BMJ. 2014 Oct 24;349:g6435. doi: 10.1136/bmj.g6435. — View Citation

Sedgwick P. What is a crossover trial? BMJ. 2014 May 9;348:g3191. doi: 10.1136/bmj.g3191. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics Parameter	Maximum plasma concentration (Cmax)	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
Primary	Pharmacokinetics Parameter	Area Under Curve from 0 to 72 hours (AUCt)	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

External Links

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