A Multinational Study to Evaluate the Effects of a 28-Day Oral Contraceptive on Hemostatic Parameters in Healthy Women

A Multinational, Multicenter, Randomized, Open-Label Study to Evaluate the Impact of DR-102 Compared to a 28-day Standard Oral Contraceptive Regimen, on Hemosatic Parameters in Healthy Women

This study is being conducted to evaluate the impact of DR-102, a 28-day oral contraceptive compared to a standard 28-day oral contraceptive regimen on hemostatic parameters in healthy women.

Study Overview

• Status: Completed
• Conditions: Oral Contraceptive; Hemostasis
• Intervention / Treatment: Drug: desogestrel/ethinyl estradiol and ethinyl estradiol; Drug: desogestrel/ethinyl estradiol

• Study Type: Interventional
• Enrollment (Actual): 293
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45127
    • Teva Investigational Site 32064
  • Frankfurt, Germany, 60311
    • Teva Investigational Site 32065
  • Frankfurt am Main, Germany, 60439
    • Teva Investigational Site 32066
  • Hamburg, Germany, 22159
    • Teva Investigational Site 32062
  • Hamburg, Germany, 22359
    • Teva Investigational Site 32063
  • Magdeburg, Germany, 39112
    • Teva Investigational Site 32061
• Israel
  • Givataim, Israel, 53425
    • Teva Investigational Site 80013
  • Haifa, Israel, 34466
    • Teva Investigational Site 80015
  • Modi'in, Israel, 71705
    • Teva Investigational Site 80017
  • RishonLe'zio, Israel
    • Teva Investigational Site 80014
  • Tel-Aviv, Israel, 62304
    • Teva Investigational Site 80018
  • Tel-Aviv, Israel, 69379
    • Teva Investigational Site 80016
• Italy
  • Brescia, Italy, 25123
    • Teva Investigational Site 30014
  • Cagliari, Italy, 09124
    • Teva Investigational Site 30009
  • Catania, Italy, 95123
    • Teva Investigational Site 30012
  • Napoli, Italy, 80131
    • Teva Investigational Site 30013
  • Pavia, Italy, 27100
    • Teva Investigational Site 30010
  • Pisa, Italy, 56126
    • Teva Investigational Site 30007
  • Siena, Italy, 53100
    • Teva Investigational Site 30016
• Spain
  • Barcelona, Spain, 08025
    • Teva Investigational Site 31017
  • Barcelona, Spain, 08028
    • Teva Investigational Site 31015
  • Barcelona, Spain, 08035
    • Teva Investigational Site 31014
  • Gava, Barcelona, Spain, 08850
    • Teva Investigational Site 31016
  • Lugo, Spain, 27002
    • Teva Investigational Site 31012
  • Madrid, Spain, 28001
    • Teva Investigational Site 31010
  • Madrid, Spain, 28009
    • Teva Investigational Site 31011
  • Vitoria-Gasteiz, Spain, 01004
    • Teva Investigational Site 31009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Premenopausal, non-pregnant, non-lactating women age 18-40 years old
• Body Mass Index (BMI) ≥18 kg/m² and <30 kg/m²
• Regular spontaneous menstrual cycle
• Others as dictated by FDA-approved protocol

Exclusion Criteria:

• Any condition which contraindicates the use of combination oral contraceptives
• Any history of, or active, deep vein thrombosis, pulmonary embolism, or arterial thromboembolic disease within one year of screening
• Thrombophlebitis or thromboembolic disorders; known or suspected clotting disorders; thrombogenetic valvulopathies or rhythm disorders
• Others as dictated by FDA-approved protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment I: (DR-102); 21 days of combination active pills (containing 150 mcg desogestrel [DSG]/20 mcg ethinyl estradiol [EE]), followed by 7 days of 10 mcg EE, taken orally for 6 consecutive 28-day cycles	Drug: desogestrel/ethinyl estradiol and ethinyl estradiol
Active Comparator: Treatment II; 21 days combination active pills (containing 150 mcg DSG/20 mcg EE), taken orally and followed by 7 days of no treatment for a total of 6 consecutive 28-day cycles	Drug: desogestrel/ethinyl estradiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Prothrombin Fragment 1 + 2 Levels	Normal range for this hemostatic parameter was 41 to 372 pmol/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in D-Dimer	Normal range for this hemostatic parameter was 0 to 729 mcg/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Period in Protein S Total Antigen	The normal range for this hemostatic parameter was 50% to 147%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Protein C Activity	The normal range for this hemostatic parameter was 70% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Antithrombin	Normal range for this hemostatic parameter was 75% to 130%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor II Activity	Normal range for this hemostatic parameter was 70% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VII	Normal range for this hemostatic parameter was 60% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VIII	Normal range for this hemostatic parameter was 50% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Activated Partial Thromboplastin Time (APTT)-Based Activated Protein-C (APC) Resistance	This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 2.00 to 3.36. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Endogenous Thrombin Potential (EPT)-Based Activated Protein-C (APC) Resistance	This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 0.32 to 1.79. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Corticosteroid-Binding Globulin	Normal range for this adrenal parameter was 1906.448 to 4520.504 mg/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Serum Random Total Cortisol	Normal range for this adrenal parameter was 85.6 to 618.2 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Thyroid-Stimulating Hormone (TSH)	Normal range for this parameter was 0.35 to 5.5 mIU/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Sex Hormone Binding Globulin	Normal range for this parameter was 28 to 146 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.	Baseline through Month 6

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Chair: Teva Women's Health Research Protocol Chair, Teva Women's Health Research

Publications and helpful links

General Publications

• Peters K, Gordon N, Ricciotti N, Hsieh J, Howard B, Weiss H. Hemostatic effects of two desogestrel-containing combined oral contraceptive regimens: a multinational, multicenter, randomized, open-label study. Clin Exp Obstet Gynecol. 2016;43(3):334-40.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2011
• Primary Completion (Actual): September 30, 2012
• Study Completion (Actual): September 30, 2012

Study Registration Dates

• First Submitted: July 1, 2011
• First Submitted That Met QC Criteria: July 5, 2011
• First Posted (Estimate): July 6, 2011

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Contraception; Hemostasis; Blood Coagulation
• 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; Estradiol; Ethinyl Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Desogestrel
• Other Study ID Numbers: DSG-HSP-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No