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

• Sponsor: PT Sydna Farma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04964193
• Collaborator: PT Pharma Metric Labs (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.5
• Patients Per Site Per Month: 3.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Drug Use	Drug: Elzsa film-coated tablet; Drug: Diane-35 Sugar-coated tablet	N/A

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.Randomized, single blind, two-period, single dose, crossover study with three weeks washout period in 24 healthy female subjects under fasting condition.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Bioequivalence Study of 2 mg Cyproterone Acetate and 0.035 mg Ethinyl Estradiol in Indonesian Healthy Females
• Actual Study Start Date: Mar 12, 2019
• Actual Primary Completion Date: Jul 4, 2019
• Actual Study Completion Date: Sep 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elzsa film-coated tablet Participants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water	Drug: Elzsa film-coated tablet; Administered with 240 mL of water; Other Names: 2 mg cyproterone acetate + 0.035 mg ethinylestradiol
Active Comparator: 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	Drug: Diane-35 Sugar-coated tablet; Administered with 240 mL of water; Other Names: 2 mg cyproterone acetate + 0.035 mg ethinylestradiol

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics Parameter [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)

2. Pharmacokinetics Parameter [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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 54 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PT Pharma Metric Labs	Multiple Locations	Jakarta	Indonesia	10520

Sponsors and Collaborators

• PT Sydna Farma
• PT Pharma Metric Labs

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 12, 2019

More Information

Additional Information:

• (accessed on Sep 18, 2020)
• (accessed on Sep 18, 2020)

Publications

None provided.

• Responsible Party: PT Sydna Farma
• ClinicalTrials.gov Identifier: NCT04964193
• Other Study ID Numbers: 440/STD/PML/2018
• First Posted: Jul 16, 2021
• Last Update Posted: Jan 31, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by PT Sydna Farma: cyproterone acetate; ethinyl estradiol; bioequivalence; cross-over design study; pharmacokinetics; Indonesian healthy female
• Additional relevant MeSH terms: Cyproterone Acetate; Ethinyl Estradiol; Cyproterone; Cyproterone acetate, ethinyl estradiol drug combination

Study Results

Participant Flow

Arm/Group Title	Test Drug First, Then Reference Drug	Diane-35 Sugar-coated Tablet
Arm/Group Description	New (test) Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose in the first intervention period, and marketed (reference) Diane®-35 sugar-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose in the second intervention period (after washout period).	Marketed (reference) Diane-35 Sugar-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose in the first intervention period, and new (test) Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose in the second intervention period (after washout period).
Period Title: 1st Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: 1st Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: 1st Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Total Number of Participants
Arm/Group Description	All participants received 2 mg cyproterone acetate + 0.035 mg ethinylestradiol tablet (new and marketed)
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	24 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics Parameter
Description	Maximum plasma concentration (Cmax)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elzsa Film-coated Tablet	Diane-35 Sugar-coated Tablet
Arm/Group Description	Participants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water Elzsa film-coated tablet: Administered with 240 mL of water	Participants received Diane-35 Sugar-coated tablet ( 2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water Diane-35 Sugar-coated tablet: Administered with 240 mL of water
Measure Participants	24	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)

2. Primary Outcome

Title	Pharmacokinetics Parameter
Description	Area Under Curve from 0 to 72 hours (AUCt)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elzsa Film-coated Tablet	Diane-35 Sugar-coated Tablet
Arm/Group Description	Participants received Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water Elzsa film-coated tablet: Administered with 240 mL of water	Participants received Diane-35 Sugar-coated tablet ( 2 mg cyproterone acetate + 0.035 mg ethinylestradiol) with 240 mL of water Diane-35 Sugar-coated tablet: Administered with 240 mL of water
Measure Participants	24	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
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Elzsa Film-coated Tablet		Diane-35 Sugar-coated Tablet
Arm/Group Description	New (test) Elzsa film-coated tablet (2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose.		Marketed (reference) Diane-35 Sugar-coated tablet ( 2 mg cyproterone acetate + 0.035 mg ethinylestradiol) as a single oral dose.
All Cause Mortality
	Elzsa Film-coated Tablet		Diane-35 Sugar-coated Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Elzsa Film-coated Tablet		Diane-35 Sugar-coated Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Elzsa Film-coated Tablet		Diane-35 Sugar-coated Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/24 (25%)		9/24 (37.5%)
Gastrointestinal disorders
Nausea	0/24 (0%)	0	1/24 (4.2%)	1
Pharyngitis	1/24 (4.2%)	1	0/24 (0%)	0
General disorders
Dizziness	1/24 (4.2%)	1	2/24 (8.3%)	2
Drowsiness	1/24 (4.2%)	1	1/24 (4.2%)	1
Headache	1/24 (4.2%)	1	2/24 (8.3%)	2
Toothache	1/24 (4.2%)	1	0/24 (0%)	0
Syncope	1/24 (4.2%)	1	0/24 (0%)	0
Renal and urinary disorders
Frequently Urination	0/24 (0%)	0	1/24 (4.2%)	1
Reproductive system and breast disorders
Breast tenderness or Breast discomfort	1/24 (4.2%)	1	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Flu like symptoms (Runny rose nose, headache)	0/24 (0%)	0	1/24 (4.2%)	1
Sneezing	0/24 (0%)	0	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.