Phase III, Multicenter, Open-Label, Single-Arm Clinical Trial to Evaluate the Contraceptive Efficacy and Safety of a New Concentration of an Antiandrogenic Progestogen Combined With a Reduced-Dose Estrogen in Women of Childbearing Potential
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,600
- 主要终点
- Contraceptive Efficacy Assessed by Pearl Index in Participants Aged ≤35 Years
研究概览
简要总结
This study is a Phase III, multicenter, open-label, single-arm clinical trial designed to evaluate the contraceptive efficacy and safety of a new formulation containing N0999 in women of childbearing potential. Approximately 1,600 post-menarche women aged 14 to 45 years who are candidates for systemic hormonal contraception are expected to be enrolled.
All participants will receive the investigational product, consisting of N0999 administered in a 24+4 regimen. Each treatment cycle consists of 24 active tablets followed by 4 inactive tablets. Participants will receive treatment for 13 consecutive 28-day cycles, corresponding to approximately 52 weeks of treatment. Total study participation, including screening and follow-up, is expected to be approximately 58 weeks.
The primary objective of the study is to evaluate contraceptive efficacy over 13 treatment cycles using the Pearl Index in participants aged 35 years or younger. Secondary objectives include assessing the Pearl Index in the overall study population and in participants older than 35 years, evaluating the method-failure Pearl Index based on correct and consistent use, and estimating cumulative pregnancy rates using Life Table Analysis.
Additional objectives include evaluating cycle control, including withdrawal bleeding, intermenstrual spotting, amenorrhea, and bleeding duration, as well as participant satisfaction with study treatment. Exploratory assessments of clinical and laboratory signs of hyperandrogenism will also be performed.
The safety and tolerability of the investigational product will be evaluated throughout the study by monitoring adverse events, serious adverse events, adverse events of special interest, safety-related discontinuations, clinically relevant findings, and laboratory assessments. An Independent Data and Safety Monitoring Committee will oversee participant safety during the trial.
Participants who wish to become pregnant after completing treatment may participate in an additional exploratory follow-up period of up to 12 months to characterize the return of spontaneous menstruation
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Ability to voluntarily participate in the study and provide written informed consent (and assent, where applicable) before the performance of any study-specific procedures.
- •Biological female aged 14 to 45 years (inclusive) at the time of informed consent/assent.
- •Post-menarche for at least 1 year.
- •Regular menstrual cycles lasting 21 to 35 days documented during the 3 months prior to screening (for women not using hormonal contraception at screening).
- •Sexually active with a male partner, with a minimum frequency of one vaginal intercourse per month.
- •Male partner who is not known to be subfertile or infertile, has not undergone vasectomy, and is not known to be HIV-positive.
- •Male partner without homosexual intercourse within the previous 5 years without a subsequent negative HIV test and without shared needle use without a subsequent negative HIV test.
- •No history of investigated or diagnosed infertility.
- •Willing to refrain from using another contraceptive method during study treatment.
- •Adequate washout period from previous contraceptive methods:
- •≥12 months for depot medroxyprogesterone acetate (DMPA, Depo-Provera®);
- •≥6 months for monthly combined injectable contraceptives;
- •≥3 months for subdermal implants or levonorgestrel-releasing intrauterine systems;
- •≥2 spontaneous menstrual cycles for combined oral contraceptives or oral progestogens, or direct switch on the day following the last active tablet, according to the switcher classification.
- •Body mass index (BMI) ≥16 kg/m².
- •Participants aged 25 years or older must provide documentation of cervical cytology without clinically relevant abnormalities within the previous 18 months or a negative HPV DNA test within the previous 5 years.
- •Participants aged 40 years or older must provide documentation of bilateral mammography without findings suspicious for malignancy within the previous 24 months.
- •Willing and able to comply with study requirements, including use of the participant diary and attendance at scheduled visits.
- •Willing to use the investigational product as the primary contraceptive method during the 13 treatment cycles, without routine need for a backup contraceptive method.
排除标准
- •Confirmed or suspected pregnancy, or plans to become pregnant within the next 12 weeks.
- •Childbirth, abortion, or breastfeeding within the previous 3 months.
- •Personal history of cardiovascular disease, including myocardial infarction, stroke, coronary artery disease, peripheral arterial disease, venous thromboembolic disease (deep vein thrombosis or pulmonary embolism), arterial thromboembolic disease, or any condition that increases the risk of these disorders.
- •Known history of cardiomyopathy, heart failure, or clinically significant cardiac arrhythmia requiring continuous antiarrhythmic therapy.
- •Uncontrolled hypertension (systolic blood pressure >130 mmHg or diastolic blood pressure >80 mmHg) despite antihypertensive treatment, or requiring four or more classes of antihypertensive medications for adequate control.
- •Uncontrolled diabetes mellitus (history of HbA1c >7.0%) despite treatment with antihyperglycemic medications.
- •Uncontrolled dyslipidemia (history of LDL cholesterol >190 mg/dL and/or triglycerides >500 mg/dL) despite lipid-lowering therapy.
- •Known personal history of thrombophilia.
- •Current smoking of more than 5 cigarettes per day.
- •Any known condition that may worsen with hormonal treatment or interfere with study conduct or interpretation of results, including herpes gestationis, idiopathic jaundice during a previous pregnancy, otosclerosis, Sydenham's chorea, porphyria, or biliary disorders (including cholestasis or gallstones), or systemic lupus erythematosus.
- •History or current diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis), moderate or severe hepatic insufficiency, hemolytic uremic syndrome, headache with focal neurological symptoms, epilepsy, asthma requiring chronic oral corticosteroid use, multiple sclerosis, chorea minor, tetany, endometriosis, mastopathy, current premenstrual dysphoric disorder, sickle cell anemia, pancreatitis, diabetic vascular complications, or major depressive disorder.
- •Significant psychiatric condition or suicide risk, in the opinion of the investigator.
- •Hypersensitivity to any component of the investigational product.
- •History of alcohol and/or drug abuse.
- •Malignancy within the previous 5 years, except non-melanoma skin cancer, or any history of hormone-dependent malignancy or current suspicion of malignancy, including meningioma and hepatic tumors.
- •Organ transplantation within the previous 5 years or chronic disease with anticipated transplantation.
- •Use within the previous 90 days of medications known to interfere with cytochrome P450-mediated hepatic metabolism, including carbamazepine, phenytoin, primidone, oxcarbazepine, topiramate, rifampicin, ritonavir, or St. John's wort-containing products.
- •Use within the previous 90 days of direct-acting antiviral medications containing ombitasvir, paritaprevir, dasabuvir, or combinations of these agents.
- •Undiagnosed vaginal bleeding.
- •Abnormal breast examination findings or other clinically significant gynecological findings that, in the investigator's opinion, could worsen with oral contraceptive use.
- •Participant living with HIV infection or with a history of unresolved hepatitis B or hepatitis C infection.
- •Participation in another clinical trial within the previous 12 months, unless the investigator considers that direct benefit to the participant may be expected.
- •Any other clinical condition or laboratory abnormality that, in the investigator's opinion, makes the participant unsuitable for study participation.
研究组 & 干预措施
N0999
干预措施: Cyproterone Acetate 2 mg and Ethinyl Estradiol 0.02 mg (Drug)
结局指标
主要结局
Contraceptive Efficacy Assessed by Pearl Index in Participants Aged ≤35 Years
时间窗: 52 weeks (12 months), corresponding to 13 consecutive 28-day treatment cycles
Contraceptive efficacy of cyproterone acetate 2 mg plus ethinyl estradiol 0.02 mg will be evaluated using the Pearl Index in the subgroup of participants aged 35 years or younger in the intention-to-treat population with evaluable cycles. The primary analysis aims to demonstrate a 95% confidence interval upper limit of less than 5.0 pregnancies per 100 woman-years.
次要结局
未报告次要终点