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Trial record 27 of 100 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

"E4/DRSP Endocrine Function, Metabolic Control and Hemostasis Study"

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ClinicalTrials.gov Identifier: NCT02957630
Recruitment Status : Completed
First Posted : November 8, 2016
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Estetra

Brief Summary:
The proposed study will provide an assessment of the effect of this combination on endocrine function, metabolic control and hemostasis during 6 treatment cycles. This will be compared to the effects of two reference COCs.

Condition or disease Intervention/treatment Phase
Contraception Liver Metabolism Hemostasis Parameter Drug: 15 mg E4/3 mg DRSP Drug: 30 mcg EE/150 mcg LNG Drug: 20 mcg EE/3 mg DRSP Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Single Center, Randomized,Open-label,Controlled, Three-arm Study to Evaluate the Effect of a New Combined Oral Contraceptive (COC) Containing 15 mg Estetrol (E4) and 3 mg Drospirenone (DRSP) and of Two Reference COCs Containing Either 30 mcg Ethinylestradiol (EE) and 150 mcg Levonorgestrel (LNG) or 20 mcg EE and 3 mg DRSP on Endocrine Function, Metabolic Control and Hemostasis During 6 Treatment Cycles
Study Start Date : September 2016
Actual Primary Completion Date : October 9, 2017
Actual Study Completion Date : October 9, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 15 mg E4/3 mg DRSP
15 mg estetrol/3 mg drospirenone combined oral contraceptive
Drug: 15 mg E4/3 mg DRSP
15 mg E4 combined with 3 mg DRSP administered in a 24/4-day regimen (i.e. 24 days of pink active tablets followed by 4 days of white placebo tablets). One tablet per day orally for 6 treatment cycles.
Other Name: 15 mg estetrol and 3 mg drospirenone

Active Comparator: 30 mcg EE/150 mcg LNG
30 mcg ethinylestradiol/150 mcg levonorgestrel combined oral contraceptive
Drug: 30 mcg EE/150 mcg LNG
30 mcg EE combined with 150 mcg LNG administered in a 21/7‑day regimen (i.e. 21 days of yellow active tablets followed by 7 days of white placebo tablets). One tablet per day orally for 6 treatment cycles.
Other Name: 30 mcg ethinylestradiol and 150 mcg levonorgestrel

Active Comparator: 20 mcg EE/3 mg DRSP
20 mcg ethinylestradiol/3 mg drospirenone combined oral contraceptive
Drug: 20 mcg EE/3 mg DRSP
20 mcg EE combined with 3 mg DRSP administered in a 24/4‑day regimen (i.e. 24 days of pink active tablets followed by 4 days of white placebo tablets). One tablet per day orally for 6 treatment cycles.
Other Name: 20 mcg ethinylestradiol and 3 mg drospirenone




Primary Outcome Measures :
  1. Plasma concentration of prothrombin fragment 1+2 [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  2. Plasma concentration of APC resistance (ETP-based, APTT-based) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  3. Plasma concentration of D-dimer [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  4. Plasma concentration of factor VII [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  5. Plasma concentration of factor VIII [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  6. Plasma concentration of von Willebrand factor [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  7. Plasma concentration of factor II [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  8. Plasma concentration of antithrombin [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  9. Plasma concentration of free and total Protein S [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  10. Plasma concentration of protein C [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  11. Plasma concentration of plasminogen activator inhibitor type-1 (PAI-1) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  12. Plasma concentration of tissue type plasminogen activator (t-PA) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  13. Plasma concentration of plasminogen [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  14. Plasma concentration of free tissue factor pathway inhibitor (TPFI) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  15. Plasma concentration of E-selectin [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  16. Plasma concentration of fibrinogen [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  17. Serum concentration of insulin [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for Cycles 3 and 6 (1 cycle = 28 days). ]
  18. Serum concentration of glucose [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for Cycles 3 and 6 (1 cycle = 28 days). ]
  19. Serum concentration of C-peptide [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for Cycles 3 and 6 (1 cycle = 28 days). ]
  20. Plasma concentration of glycated hemoglobin (HbA1c) [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  21. Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  22. Oral glucose tolerance test (OGTT) [ Time Frame: At 0 (pre-glucose challenge), 30, 60, 90, 120 and 180 minutes after glucose challenge during pretreatment Cycle; at 0 (pre-glucose challenge), 30, 60, 90, 120 and 180 minutes after glucose challenge during Cycles 3 and 6 (1 cycle = 28 days). ]
  23. Serum concentration of prolactin [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  24. Serum concentration of follicle-stimulating hormone (FSH) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  25. Serum concentration of luteinizing hormone (LH) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  26. Serum concentration of estradiol (E2) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  27. Serum concentration of progesterone (P) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  28. Serum concentration of thyroïd stimulating hormone (TSH) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  29. Serum concentration of free thyroxine (fT3)/free triiodothyronine (fT4) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  30. Serum concentration of dihydroepiandrostenedione (DHEAS) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  31. Serum concentration of androstenedione [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  32. Serum concentration of total testosterone (T) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  33. Serum concentration of dihydrotestosterone (DHT) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  34. Serum concentration of total cortisol [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  35. Serum concentration of aldosterone [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  36. Serum concentration of high density lipoprotein (HDL)-cholesterol [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  37. Serum concentration of low density lipoprotein (LDL)-cholesterol [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  38. Serum concentration of total cholesterol [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  39. Serum concentration of triglycerides [ Time Frame: At screening, between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  40. Serum concentration of lipoprotein (a) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  41. Serum concentration of apoliporotein A1 [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  42. Serum concentration of apoliporotein B [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  43. Serum concentration of C-reactive protein [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  44. Serum concentration of corticosteroid binding globulin (CBG) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  45. Serum concentration of sex hormone binding globulin (SHBG) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  46. Serum concentration of thyroxin binding globulin (TBG) [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]
  47. Serum concentration of angiotensinogen [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle, and between Days 18 and 21 for the Cycles 3 and 6 (1 cycle = 28 days). ]

Secondary Outcome Measures :
  1. Number of subjects with adverse events as a measure of safety and tolerability [ Time Frame: From up to 28 days before randomization to maximum Day 4 of the Cycle 7 (1 cycle = 28 days). ]
  2. Serum concentration of lactate dehydrogenase (LDH) 1 and 2 [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle and between Days 18 and 21 for the Cycle 6 (1 cycle = 28 days) ]
  3. Serum concentration of tropinin T and I [ Time Frame: Between Days 18 and 21 for the pretreatment Cycle and between Days 18 and 21 for the Cycle 6 (1 cycle = 28 days) ]
  4. Electrocardiogram (ECG) parameters [ Time Frame: At screening and between Days 18 and 21 for Cycle 6 (1 cycle = 28 days). ]
    The following ECG parameters will be recorded: heart rate, PR-interval, QRS-duration, QT-interval, QTc interval (Fridericias's)

  5. Echocardiographic parameters [ Time Frame: At screening and between Days 18 and 21 for Cycle 6 (1 cycle = 28 days). ]
  6. Change from baseline to end of treatment in the different items of the menstrual distress questionnaires (MDQ) form C [ Time Frame: At pretreatment Cycle and between Days 18 and 21 for Cycle 6 (1 cycle = 28 days). ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult woman
  • Negative pregnancy test at subject screening and randomization
  • Aged 18-50 years (inclusive) at the time of signing the ICF
  • Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, gynecological examination, clinical laboratory, ECG, echocardiography and vital signs
  • BMI from 18.0 to 30.0 kg/m², inclusive, at time of screening visit
  • Able to fulfil the requirements of the protocol and have indicated a willingness to participate in the study by providing written informed consent

Exclusion Criteria:

  • Known hypersensitivity to any of the investigational product ingredients
  • Smoking if > 35 years old
  • Dyslipoproteinemia or use of antilipidemic agent
  • Known diabetes mellitus
  • Current use of antidiabetic drugs, including insulin
  • Arterial hypertension
  • Any condition associated with an increased risk of venous thromboembolism and/or arterial thromboembolism.
  • Any condition associated with abnormal uterine/vaginal bleeding.
  • Presence of an undiagnosed breast mass
  • Current symptomatic gallbladder disease
  • History of pregnancy- or COC-related cholestasis
  • Presence or history of severe hepatic disease
  • Presence or history of pancreatitis if associated with hypertriglyceridemia
  • Porphyria
  • Presence or history of benign liver tumors (focal nodular hyperplasia and hepatocellular adenoma)
  • Presence of renal impairment (glomerular filtration rate [GFR] <60 mL/min/1.73m²)
  • Hyperkalemia or presence of conditions that predispose to hyperkalemia
  • Presence or history of hormone-related malignancy
  • History of non-hormone-related malignancy within 5 years before screening; subjects with a non-melanoma skin cancer are allowed in the study
  • Use of drugs potentially triggering interactions with COCs
  • History of alcohol or drug abuse within 12 months prior to screening
  • Presence or history of thyroid disorders
  • Participation in another investigational drug clinical study within 1 month (30 days) or have received an investigational drug within the last 3 months (90 days) prior to randomization. Subjects who participated in an oral contraceptive clinical study using Food and Drug Administration (FDA)/European Union (EU) approved active ingredients, may be randomized 2 months (60 days) after completing the preceding study
  • Sponsor, contract research organization (CRO) or Principal Investigator's (PI's) site personnel directly affiliated with this study
  • Is judged by the PI to be unsuitable for any reason

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02957630


Locations
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Netherlands
Dinox BV
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
Estetra
Investigators
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Principal Investigator: Christine Klipping Dinox BV

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Responsible Party: Estetra
ClinicalTrials.gov Identifier: NCT02957630     History of Changes
Other Study ID Numbers: MIT-Es0001-C201
2016-001316-37 ( EudraCT Number )
First Posted: November 8, 2016    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Estetra:
Estetrol (E4)
Drospirenone (DRSP)
Ethinylestradiol (EE)
Levonorgestrel (LNG)
Oral contraceptive
Prevention of pregnancy
Hemostasis
Metabolism

Additional relevant MeSH terms:
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Ethinyl Estradiol
Drospirenone
Contraceptive Agents
Levonorgestrel
Contraceptives, Oral
Hemostatics
Contraceptives, Oral, Combined
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Coagulants
Contraceptives, Oral, Synthetic
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents