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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Estetra
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Serum concentration of C-peptide
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
15 mg E4/3 mg DRSP
15 mg estetrol/3 mg drospirenone combined oral contraceptive
干预措施: 15 mg E4/3 mg DRSP (Drug)
30 mcg EE/150 mcg LNG
30 mcg ethinylestradiol/150 mcg levonorgestrel combined oral contraceptive
干预措施: 30 mcg EE/150 mcg LNG (Drug)
20 mcg EE/3 mg DRSP
20 mcg ethinylestradiol/3 mg drospirenone combined oral contraceptive
干预措施: 20 mcg EE/3 mg DRSP (Drug)
结局指标
主要结局
Serum concentration of C-peptide
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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).
次要结局
- 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).)
- 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).)