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

NCT04964193 | Completed Results DMC

• 1 other identifier: 440/STD/PML/2018
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Use

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (2)

Elzsa film-coated tablet

EXPERIMENTAL

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

Drug: Elzsa film-coated tablet

Diane-35 Sugar-coated tablet

ACTIVE COMPARATOR

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

Drug: Diane-35 Sugar-coated tablet

Interventions

Elzsa film-coated tablet DRUG

Administered with 240 mL of water

Also known as: 2 mg cyproterone acetate + 0.035 mg ethinylestradiol

Elzsa film-coated tablet

Diane-35 Sugar-coated tablet DRUG

Administered with 240 mL of water

Also known as: 2 mg cyproterone acetate + 0.035 mg ethinylestradiol

Diane-35 Sugar-coated tablet

Eligibility Criteria

• Age: 19 Years - 54 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PT Sydna Farma: lead
• PT Pharma Metric Labs: collaborator

Study Sites (1)

PT Pharma Metric Labs

Multiple Locations, Jakarta Special Capital Region, 10520, Indonesia

Location

Related Publications (10)

• 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.

  PMID: 17426085 RESULT

• 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.

  PMID: 22795636 RESULT

• 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.

  PMID: 14667981 RESULT

• 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.

  PMID: 28447864 RESULT

• 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.

  PMID: 949892 RESULT

• 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.

  PMID: 8131397 RESULT

• 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.

  PMID: 26253465 RESULT

• 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.

  PMID: 15580599 RESULT

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

  PMID: 25134118 RESULT

• 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.

  PMID: 25954990 RESULT

Related Links

• (accessed on Sep 18, 2020)

MeSH Terms

Interventions

Cyproterone Acetate; Ethinyl Estradiol

Intervention Hierarchy (Ancestors)

Cyproterone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Norpregnatrienes; Norpregnanes; Norsteroids; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Pharma Metric Labs
• Organization: Pharma Metric Labs, Indonesia

nabila.sutanto@pharmametriclabs.com

+62 21 4265310

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: July 16, 2021
• Study Start: March 12, 2019
• Primary Completion: July 4, 2019
• Study Completion: September 26, 2019
• Last Updated: January 31, 2022
• Results First Posted: January 31, 2022

Record last verified: 2022-01

Locations

ID (1)