Drug UseNCT04964193

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

A study testing Elzsa film-coated tablet and Diane-35 Sugar-coated tablet in people with Drug Use, run by PT Sydna Farma at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 19 to 54 years, women onlyHealthy volunteers can take part
Conditions the study is for: Drug Use
What is being tested?: Elzsa film-coated tablet and Diane-35 Sugar-coated tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteIndonesia
Study dates: 12 Mar 2019to 26 Sep 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 to 54 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

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)

Show all 9Show fewer

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

Who cannot join

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.

Show all 12Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Indonesia1 site

PT Pharma Metric Labs
Multiple Locations, Jakarta Special Capital Region, 10520

Other trials in Indonesia

About this study

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

Read the 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

Conditions: Drug Use
Being tested: Elzsa film-coated tablet, Diane-35 Sugar-coated tablet
Keywords: cyproterone acetate, ethinyl estradiol, bioequivalence, cross-over design study, pharmacokinetics, Indonesian healthy female

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Elzsa film-coated tabletDrug
Also called 2 mg cyproterone acetate + 0.035 mg ethinylestradiol
Administered with 240 mL of water
Diane-35 Sugar-coated tabletDrug
Also called 2 mg cyproterone acetate + 0.035 mg ethinylestradiol
Administered with 240 mL of water

Study groups in NCT04964193
Study group	Role	What they receive
Elzsa film-coated tablet	Experimental	Participants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water Receives: 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 Receives: Drug: Diane-35 Sugar-coated tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetics Parameter
Maximum plasma concentration (Cmax)
Measured: 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)
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Mar 201926 Sep 2019

First posted16 Jul 2021
Study start12 Mar 2019
Primary completion4 Jul 2019
Study completion26 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Drug UseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04964193
Sponsor's protocol ID: 440/STD/PML/2018
Status last verified: Jan 2022
First submitted: 14 Apr 2021
Last updated: 31 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 17426085
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.
PubMed 22795636
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.
PubMed 14667981
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.
PubMed 28447864
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.
PubMed 949892
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.
PubMed 8131397
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.
PubMed 26253465
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.
PubMed 15580599
Sedgwick P. What is a crossover trial? BMJ. 2014 May 9;348:g3191. doi: 10.1136/bmj.g3191. No abstract available.
PubMed 25134118
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.
PubMed 25954990

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Bioequivalence Study of 2 mg Cyproterone Acetate and 0.035 mg Ethinyl Estradiol in Indonesian Healthy Females
ClinicalTrials.gov ID: NCT04964193
Acronym / sponsor ID: 440/STD/PML/2018
Conditions: Drug Use
Keywords: cyproterone acetate, ethinyl estradiol, bioequivalence, cross-over design study, pharmacokinetics, Indonesian healthy female
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: PT Sydna FarmaIndustry (pharma, biotech, devices)
Collaborators: PT Pharma Metric Labs
Study start: 12 Mar 2019 (actual)
Primary completion: 4 Jul 2019 (actual)
Study completion: 26 Sep 2019 (actual)
First posted: 16 Jul 2021 (actual)
Results: Posted 31 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.

Arm	Type	Receives
Elzsa film-coated tablet	Experimental	Drug: Elzsa film-coated tabletParticipants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water
Diane-35 Sugar-coated tablet	Active comparator	Drug: Diane-35 Sugar-coated tabletParticipants received Diane-35 Sugar-coated tablet ( 2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water

Who may qualify

Ages: 19 to 54 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

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)

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Elzsa film-coated tabletAlso: 2 mg cyproterone acetate + 0.035 mg ethinylestradiolAdministered with 240 mL of water	Drug	Elzsa film-coated tablet
Diane-35 Sugar-coated tabletAlso: 2 mg cyproterone acetate + 0.035 mg ethinylestradiolAdministered with 240 mL of water	Drug	Diane-35 Sugar-coated tablet

Primary outcome

Pharmacokinetics Parameter
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
Maximum plasma concentration (Cmax)
Pharmacokinetics Parameter
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
Area Under Curve from 0 to 72 hours (AUCt)

Results and safety

Results posted to the registry on 31 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Test Drug First, Then Reference Drug	12	12
Diane-35 Sugar-coated Tablet	12	12

Primary outcome: Pharmacokinetics Parameter

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. Mean (Standard Deviation). Unit: pg/mL

Measure	Elzsa Film-coated Tablet n = 24	Diane-35 Sugar-coated Tablet n = 24
Cmax of Cyproterone Acetate	17.39 (13.77)	16.20 (13.81)
Cmax of Ethinyl Estradiol	103.69 (47.42)	93.61 (47.16)

Primary outcome: Pharmacokinetics Parameter

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. Mean (Standard Deviation). Unit: pg*hr/mL

Measure	Elzsa Film-coated Tablet n = 24	Diane-35 Sugar-coated Tablet n = 24
AUC0-t of Cyproterone Acetate	132.56 (73.19)	127.54 (89.41)
AUC0-t of Ethinyl Estradiol	870.45 (383.56)	842.56 (398.66)

Adverse events

Time frame: 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. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Elzsa Film-coated Tablet	0 of 24 (0%)	6 of 24 (25%)	0 of 24
Diane-35 Sugar-coated Tablet	0 of 24 (0%)	9 of 24 (37.5%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 17426085Luque-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.
Results publication: PubMed 22795636Bhattacharya 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.
Results publication: PubMed 14667981Elger 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.
Results publication: PubMed 28447864Bitzer 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.
Results publication: PubMed 949892Speck 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.
Results publication: PubMed 8131397Kuhnz 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.
Results publication: PubMed 26253465Sedgwick 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.
Results publication: PubMed 15580599Garcia 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.
Results publication: PubMed 25134118Sedgwick P. What is a crossover trial? BMJ. 2014 May 9;348:g3191. doi: 10.1136/bmj.g3191. No abstract available.
Results publication: PubMed 25954990Sedgwick P. Randomised controlled trials: "within subject" versus "between subject" designs. BMJ. 2014 Oct 24;349:g6435. doi: 10.1136/bmj.g6435. No abstract available.
(accessed on Sep 18, 2020)Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Elzsa film-coated tablet and Diane-35 Sugar-coated tablet in people with Drug Use, run by PT Sydna Farma at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics Parameter (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04964193, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2022.