"E4/DRSP Endocrine Function, Metabolic Control and Hemostasis Study"
Phase 1
Completed
- Conditions
- Liver MetabolismContraceptionHemostasis Parameter
- Interventions
- Drug: 15 mg E4/3 mg DRSPDrug: 30 mcg EE/150 mcg LNGDrug: 20 mcg EE/3 mg DRSP
- Registration Number
- NCT02957630
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 101
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 15 mg E4/3 mg DRSP 15 mg E4/3 mg DRSP 15 mg estetrol/3 mg drospirenone combined oral contraceptive 30 mcg EE/150 mcg LNG 30 mcg EE/150 mcg LNG 30 mcg ethinylestradiol/150 mcg levonorgestrel combined oral contraceptive 20 mcg EE/3 mg DRSP 20 mcg EE/3 mg DRSP 20 mcg ethinylestradiol/3 mg drospirenone combined oral contraceptive
- Primary Outcome Measures
Name Time Method Serum concentration of C-peptide 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). Plasma concentration of glycated hemoglobin (HbA1c) 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). Oral glucose tolerance test (OGTT) 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). Serum concentration of follicle-stimulating hormone (FSH) 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). Serum concentration of free thyroxine (fT3)/free triiodothyronine (fT4) 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). Serum concentration of thyroxin binding globulin (TBG) 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). Plasma concentration of factor II 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). Plasma concentration of E-selectin 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). Plasma concentration of fibrinogen 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). Serum concentration of glucose 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). Serum concentration of thyroïd stimulating hormone (TSH) 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). Serum concentration of triglycerides 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). Serum concentration of lipoprotein (a) 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). Plasma concentration of factor VII 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). Plasma concentration of factor VIII 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). Plasma concentration of von Willebrand factor 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). Plasma concentration of antithrombin 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). Plasma concentration of free and total Protein S 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). Plasma concentration of plasminogen activator inhibitor type-1 (PAI-1) 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). Plasma concentration of tissue type plasminogen activator (t-PA) 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). Plasma concentration of plasminogen 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). Serum concentration of insulin 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). Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) 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). Plasma concentration of D-dimer 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). Plasma concentration of protein C 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). Serum concentration of total cortisol 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). Serum concentration of aldosterone 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). Plasma concentration of prothrombin fragment 1+2 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). Plasma concentration of APC resistance (ETP-based, APTT-based) 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). Plasma concentration of free tissue factor pathway inhibitor (TPFI) 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). Serum concentration of prolactin 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). Serum concentration of luteinizing hormone (LH) 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). Serum concentration of estradiol (E2) 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). Serum concentration of progesterone (P) 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). Serum concentration of dihydroepiandrostenedione (DHEAS) 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). Serum concentration of androstenedione 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). Serum concentration of apoliporotein A1 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). Serum concentration of dihydrotestosterone (DHT) 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). Serum concentration of high density lipoprotein (HDL)-cholesterol 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). Serum concentration of C-reactive protein 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). Serum concentration of corticosteroid binding globulin (CBG) 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). Serum concentration of total testosterone (T) 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). Serum concentration of low density lipoprotein (LDL)-cholesterol 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). Serum concentration of total cholesterol 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). Serum concentration of apoliporotein B 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). Serum concentration of sex hormone binding globulin (SHBG) 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). Serum concentration of angiotensinogen 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
Name Time Method Serum concentration of lactate dehydrogenase (LDH) 1 and 2 Between Days 18 and 21 for the pretreatment Cycle and between Days 18 and 21 for the Cycle 6 (1 cycle = 28 days) Serum concentration of tropinin T and I Between Days 18 and 21 for the pretreatment Cycle and between Days 18 and 21 for the Cycle 6 (1 cycle = 28 days) Number of subjects with adverse events as a measure of safety and tolerability From up to 28 days before randomization to maximum Day 4 of the Cycle 7 (1 cycle = 28 days). Electrocardiogram (ECG) parameters 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)
Echocardiographic parameters At screening and between Days 18 and 21 for Cycle 6 (1 cycle = 28 days). Change from baseline to end of treatment in the different items of the menstrual distress questionnaires (MDQ) form C At pretreatment Cycle and between Days 18 and 21 for Cycle 6 (1 cycle = 28 days).
Trial Locations
- Locations (1)
Dinox BV
🇳🇱Groningen, Netherlands