Evaluation of Ciclo 21® Effect (Levonorgestrel + Ethinyl Estradiol) Compared to Nordette®.

Pharmacodynamic Assessment to Drug Ciclo 21 (Levonorgestrel + Ethinyl Estradiol) Market by União Química Farmacêutica Nacional S/A Compared to Drug Nordette of Wieth Indústria Farmacêutica Ltda.

Assessment of the pharmacodynamic profile of the drug Ciclo 21 ®, marketed by União Química Farmacêutica Nacional S / A, compared to the drug Nordette ® Laboratory Wyeth Pharmaceutical Ltda. Through the modulation of hormonal response (inhibition of the pituitary) evidenced by measurement serum LH and FSH for 28 days, as well as by the absence of follicle formation demonstrated by transvaginal ultrasound examinations

Study Overview

• Status: Completed
• Conditions: Irregular Periods
• Intervention / Treatment: Drug: LNG+EE2; Drug: Nordette

Detailed Description

secondary objective

• Evaluation of the safety aspects of medicines such as type, frequency and intensity of adverse events between groups during the 28 day trial.

exploratory objective

• Evaluation of the pharmacokinetics of the drug administered through the dosage of serum hormone levonorgestrel and ethinyl estradiol for 28 days.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Valinhos, São Paulo, Brazil
      • LAL Clínica Pesquisa e Desenvolvimento Ltda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Comply with all study procedures, sign, initial and date back, of their own free will, the IC;
2. Women aged between 18 and 35 years, regardless of race and class;
3. Make use of safe non-hormonal method of contraception such as tubal ligation, non-hormonal IUDs or condoms, or be hysterectomised or be vasectomized sexual partner;
4. Examination of Beta-HCG negative;
5. with regular menstrual cycles every 24 to 32 days, at least the last three months;
6. present normal Pap test (current or during the past 02 years);
7. Present or vaginal examination found that the changes do not interfere in the study;
8. present levels of FSH, LH, estradiol and TT for the normal menstrual cycle, as well as normal transvaginal sonographic reports.

Exclusion Criteria:

1. Provide a contraindication to the use of steroids;
2. Use regular or prediction of drugs that interfere with the metabolism of the investigational products, such as antibiotics, anticonvulsants, anticoagulants and hypoglycemic drugs;
3. smokers or have stopped smoking less than 12 months;
4. Diabetic;
5. Toxic-dependent;
6. BMI <18 and> 25;
7. have made use of topical or systemic sex hormone for at least two months before the start of the study;
8. Background and personal or family history of thrombosis or bleeding disorders or vascular disorders or cardiovascular disease;
9. Laboratory tests, gynecological ultrasound or changed, the medical criteria;
10. Individuals with allergies or rheumatic diseases for which is indicated the use of cortico-steroid medication;
11. carry any endocrine changes, especially pituitary and gonadal and / or who are advised to use hormones;
12. with lesions or abnormalities suspected or confirmed in the gonads.
13. personal or family history of breast cancer or other hormone-dependent breast pathology;
14. with hypertension or diabetes mellitus (for drug interactions between the COC and hypoglycemic agents and antihypertensives);

a) History of nausea with oral use of COCs; p) Any condition that may interfere with the discretion of the investigator in the study data as well as being the measurement of the study be deleterious to the patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LNG+EE2; pill test contained levonorgestrel 0,15 mg and ethynil estradiol 0,03 mg per day over 21 days	Drug: LNG+EE2; Administration of one pill contained 0.15 mg of levonosgestrel and 0.03 mg of ethynil estradiol per day over 21 days.; Other Names: Ciclo 21
ACTIVE_COMPARATOR: Nordette; pill comparator contained levonorgestrel 0,15 mg and ethynil estradiol 0,03 mg per day over 21 days	Drug: Nordette; Administration of one pill contained 0.15 mg of levonosgestrel and 0.03 mg of ethynil estradiol per day over 21 days.; Other Names: LNG+EE2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy endpoint will be the changes in FSH and LH secretion induced by daily administration of the drug for 21 consecutive days during the 28 days of participation in the trial.	1, 2, 4, 7, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24 and 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of drugs: type, frequency and intensity of adverse events between groups during the 28 day trial. Exploratory investigation of the pharmacokinetics of the drug administered through the dosage of hormones in serum LNG and EE2 for 28 days.	PK: 1 (0, 1, 2, 3, 4, 5, 6, 12 e 18 hours after administration), 2, 7, 14, 21 and 28 days

Collaborators and Investigators

• Sponsor: Azidus Brasil
• Collaborators: União Química Farmacêutica Nacional S/A
• Investigators: Principal Investigator: Alexandre Frederico, PI, LAL Clínica Pesquisa e Desenvolvimento Ltda

Publications and helpful links

General Publications

• Twaddle NC, Churchwell MI, Newbold RR, Delclos KB, Doerge DR. Determination using liquid-chromatography-electrospray tandem mass spectroscopy of ethinylestradiol serum pharmacokinetics in adult Sprague-Dawley rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Aug 15;793(2):309-15. doi: 10.1016/s1570-0232(03)00331-3.
• Benagiano G, Carrara S, Filippi V. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives. Patient Prefer Adherence. 2009 Nov 3;3:131-43. doi: 10.2147/ppa.s3692.
• Crosignani PG, Testa G, Vegetti W, Parazzini F. Ovarian activity during regular oral contraceptive use. Contraception. 1996 Nov;54(5):271-3. doi: 10.1016/s0010-7824(96)00178-3.
• van Heusden AM, Fauser BC. Activity of the pituitary-ovarian axis in the pill-free interval during use of low-dose combined oral contraceptives. Contraception. 1999 Apr;59(4):237-43. doi: 10.1016/s0010-7824(99)00025-6.
• Rossmanith WG, Steffens D, Schramm G. A comparative randomized trial on the impact of two low-dose oral contraceptives on ovarian activity, cervical permeability, and endometrial receptivity. Contraception. 1997 Jul;56(1):23-30. doi: 10.1016/s0010-7824(97)00070-x.
• Hemrika DJ, Slaats EH, Kennedy JC, de Vries Robles-Korsen TJ, Schoemaker J. Pulsatile luteinizing hormone patterns in long term oral contraceptive users. J Clin Endocrinol Metab. 1993 Aug;77(2):420-6. doi: 10.1210/jcem.77.2.8345046.
• Kroll R, Reape KZ, Margolis M. The efficacy and safety of a low-dose, 91-day, extended-regimen oral contraceptive with continuous ethinyl estradiol. Contraception. 2010 Jan;81(1):41-8. doi: 10.1016/j.contraception.2009.07.003.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: November 25, 2011
• First Submitted That Met QC Criteria: November 28, 2011
• First Posted (ESTIMATE): November 29, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: hormonal response, levonorgestrel, ethinyl estradiol
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Contraceptives, Postcoital, Hormonal; Ethinyl Estradiol-Norgestrel Combination
• Other Study ID Numbers: LEEUNI0811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study data will be maked available after journal's approbation. The manuscript contained all of data it has been submitted.