Comparative Trial in Hormone Withdrawal Associated Symptoms

A Multi-centre, Randomized, Double-blind, Active Control, Parallel-group, 2-arm Study to Investigate the Effect of Ethinylestradiol / Drospirenone (0.02 mg/3 mg) Oral Contraception in a 24/4 Regimen Compared to Ethinylestradiol / Desogestrel (0.02 mg/0.15 mg) Oral Contraception in a 21/7 Regimen on Hormone Withdrawal Associated Symptoms in Otherwise Healthy Women After 4 Cycles of Treatment

This clinical research study will examine whether an oral contraceptive pill taken with a monthly hormone-free interval of 4 days reduces hormone withdrawal associated symptoms compared to an oral contraceptive pill taken with a monthly hormone-free interval of 7 days after 4 cycles of treatment.

Study Overview

• Status: Completed
• Conditions: Oral Contraceptive
• Intervention / Treatment: Drug: EE20/DRSP (YAZ, BAY86-5300); Drug: Ethinylestradiol (EE) and desogestrel (DSG) (Mercilon)

• Study Type: Interventional
• Enrollment (Actual): 592
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425ASQ
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
• Chile
  • Santiago, Chile
  • Santiago, Chile, 7510025
  • Santiago, Chile, 838-0456
  • Santiago de Chile, Chile
  • Temuco, Chile, 4790711
  • Santiago
    • Santiago de Chile, Santiago, Chile, 836-0156
• Colombia
  • Bogotá, Colombia
  • Medellín, Colombia
  • Santander
    • Bucaramanga, Santander, Colombia
• Czech Republic
  • Brno, Czech Republic, 602 00
  • Praha 2, Czech Republic, 120 00
  • Tabor, Czech Republic, 39003
• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69115
  • Bayern
    • Fürth, Bayern, Germany, 90763
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30459
  • Sachsen
    • Leipzig, Sachsen, Germany, 04207
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39126
  • Thüringen
    • Jena, Thüringen, Germany, 07747
• Italy
  • Firenze, Italy, 50134
  • Milano, Italy, 20132
  • Siena, Italy, 53100
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 135-710
  • Korea
    • Seoul, Korea, Korea, Republic of, 138-736
    • Seoul, Korea, Korea, Republic of, 100-380
• Philippines
  • Manila, Philippines
  • Pasig City, Philippines
• Portugal
  • Coimbra, Portugal, 3000-061
  • Lisboa, Portugal, 1649-035
  • Porto, Portugal, 4200-319
• Russian Federation
  • Moscow, Russian Federation, 117036
  • Moscow, Russian Federation, 123995
  • Moscow, Russian Federation, 177997
• Switzerland
  • Bern, Switzerland, 3010
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
  • Sankt Gallen
    • St. Gallen, Sankt Gallen, Switzerland, 9007
• Thailand
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330
  • Songkla, Thailand, 90110
• United Kingdom
  • Liverpool, United Kingdom, L20 5DQ
  • London, United Kingdom, W12 0HS
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS2 9AE
• Venezuela
  • Caracas, Venezuela

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects aged between 18 and 35 years (inclusive)
• Smokers with a maximum age of 30 years at time of informed consent
• Healthy female subjects requesting contraception and currently using a low-dose EE containing oral contraceptives (OC) in a 21-day regimen (for at least three months) and suffering from at least two of the hormone withdrawal associated symptoms headache, pelvic pain and bloating during all three months prior the planned baseline cycle and requiring further OC use
• To be valid for randomization, the total 7-day composite score of hormone-withdrawal symptoms during the baseline cycle must show an increase of at least 50% during Day 22 - 28 versus the 21-day composite score during Day 1 - 21 (21-day score divided by three [for normalization])
• History of regular cyclic menstrual periods

Exclusion Criteria:

• Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, or presence or history of prodrome of a thrombosis (e.g. transient ischemic attack, angina pectoris) and conditions that could increase the risk to suffer from any of the above mentioned disorders, e.g., a family history indicating a hereditary predisposition. Hereditary or acquired predisposition for venous or arterial thrombosis, such as APCresistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).
• History of migraine with focal neurological symptoms.
• Diabetes mellitus with vascular involvement.
• Obesity (Body Mass Index >32.0 kg/m2)
• Moderate to severe hypertension (repeated measurements of systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg).
• Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
• Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
• Jaundice and / or pruritus related to cholestasis (Gilbert´s syndrome excepted), or history of cholestatic jaundice associated with pregnancy or previous combined OC use
• Severe renal insufficiency or acute renal failure.
• Presence or history of liver tumors (benign or malignant), or known or suspected sex-steroid influenced malignancies or premalignant disease (e.g. of the genital organs or the breasts).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Drug: Ethinylestradiol (EE) and desogestrel (DSG) (Mercilon); 4 cycles of treatment / per cycle: 1 tablet (EE 0.02 mg / DSG 0.15 mg) daily for 21 days followed by 1 placebo tablet daily for 7 days
Experimental: Arm 1	Drug: EE20/DRSP (YAZ, BAY86-5300); 4 cycles of treatment / per cycle: 1 tablet (EE 0.02 mg / DRSP 3 mg) daily for 24 days followed by 1 placebo tablet daily for 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to cycle 4 in the sum of composite score during cycle days 22 - 28. The composite score comprises headache, pelvic pain and bloating (each measured by 7-point Likert scales).	Cycle days 22 - 28 of baseline cycle and cycle 4.

Secondary Outcome Measures

Outcome Measure	Time Frame
change from baseline to cycle 4 in the sum of individual scores during cycle days 22 - 28 (AUC of days 22 - 28 for each score),	Cycle days 22 - 28 of baseline cycle and cycle 4
change from baseline to cycle 4 in number of days, where individual hormone withdrawal symptoms are present on cycle days 22 - 28 (i.e. Likert Scale >= 1),	Cycle days 22 - 28 of baseline cycle and cycle 4
change from baseline to cycle 4 in maximum intensity of individual hormone withdrawal symptoms on cycle days 22 - 28,	Cycle days 22 - 28 of baseline cycle and cycle 4
rescue medication consumption	baseline cycle and cycle 4
bleeding pattern	reference period is 90 days.
evaluation of questionnaires: Q-LES-Q (short version)	baseline cycle and cycle 4
Adverse Event collection	up to 10 days after end of cycle 4
heart rate	up to 10 days after end of cycle 4
blood pressure	up to 10 days after end of cycle 4

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 25, 2010
• First Posted (Estimate): February 26, 2010

Study Record Updates

• Last Update Posted (Estimate): October 28, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: hormone withdrawal associated symptoms
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Ethinyl Estradiol; Desogestrel
• Other Study ID Numbers: 14567; 2009-014911-11 (EudraCT Number)