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Completed

NCT Number: NCT02957630

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

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.

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Key information

Conditions

Contraception Hemostasis Parameter Liver Metabolism

Age range

18 year–50 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Dinox BV

Groningen, 9713 GZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

15 mg E4/3 mg DRSP

Drug

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 names: 15 mg estetrol and 3 mg drospirenone

30 mcg EE/150 mcg LNG

Drug

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 names: 30 mcg ethinylestradiol and 150 mcg levonorgestrel

20 mcg EE/3 mg DRSP

Drug

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 names: 20 mcg ethinylestradiol and 3 mg drospirenone

Primary outcomes

  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 outcomes

  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).

Sponsors and collaborators

Lead sponsor

Estetra

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Nov 8, 2016
Registry last updated
Feb 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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