A Phase 1 Clinical Trial to Evaluate the Pharmacokinetics, Removability, Safety, and Tolerability of Casea S Contraceptive Implants
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- FHI 360
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum observed serum concentration (Cmax)
研究概览
简要总结
This is a single-center, two-part, Phase 1 study to evaluate the pharmacokinetics (PK) of ENG, removability, safety, and tolerability of Casea S pellets inserted subdermally in healthy women of reproductive age. The goal is to select for further investigation a dose of Casea S that is both safe and has a PK profile consistent with contraceptive protection for at least 78 weeks.
详细描述
In Part 1 of this study, four women will each have a single Casea S pellet (22.2 mg ENG) inserted into the inner aspect of the non-dominant upper arm after a negative urine pregnancy test. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed.
In Part 2 of this study, approximately sixteen women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants may be included in the study if they meet all of the following criteria:
- •willing and able to provide signed informed consent
- •female between 18 to 45 years of age (inclusive)
- •healthy based on results of medical evaluation including medical history, vital signs, and physical exam
- •has regular menstrual cycle (21 to 35 days)
- •not at risk for pregnancy (i.e., sterilized)
- •has a Body Mass Index (BMI) of 18 to 29.9
- •provides normal mammogram results within the last year before enrollment for women 40 or older
- •is willing and able to comply with all study requirements and return to the investigational site for the follow-up procedures and assessments as specified in this protocol
- •Part 2 participants only: has daily access to a smartphone, tablet, or computer with internet access.
排除标准
- •Participants will be excluded from participating in this study if they meet any of the following criteria:
- •has multiple risk factors for cardiovascular disease (e.g., smoking, diabetes, obesity, hypertension, high LDL (low density lipoprotein), or high triglyceride levels)
- •has current or history of ischemic heart disease or cerebrovascular disease
- •has current or previous thromboembolic disorders
- •has systemic lupus erythematosus
- •has rheumatoid arthritis on immunosuppressive therapy
- •has migraine with aura
- •has undiagnosed abnormal vaginal bleeding
- •has known or suspected breast cancer, history of breast cancer or other progestin-sensitive cancer
- •has current or history of cervical cancer
- •has cirrhosis, liver tumors (benign or malignant), or active liver disease
- •has one or more baseline liver function test(s) above the local laboratory's normal range
- •has a hemoglobin <10.5 g/dL
- •has used any injectable contraceptive in the past 6 months
- •has used any of the following medications within 4 weeks before enrollment:
- •any investigational drug
- •prohibited drugs (listed in Section 6.3.3.4.4.1 of the study protocol)
- •oral contraceptives, contraceptive ring, or patch
- •levonorgestrel intrauterine device (LNG IUD) or contraceptive implant
- •is pregnant
- •is currently breastfeeding
- •desires to become pregnant in the subsequent 30 months
- •has been pregnant in last 3 months
- •is using or planning to use prohibited drugs for their intended study duration
- •has abnormal cervical cytology requiring treatment
- •has known sensitivity to ENG
- •plans to move to another location in the next 30 months
- •is participating in any other clinical trial with a biomedical intervention
- •has any condition (social or medical), that in the opinion of the site investigator would make study participation unsafe, would interfere with adherence to the clinical study requirements, or complicate data interpretation
研究组 & 干预措施
Single Casea S pellet
In Part 1 of this study, four women will each have a single Casea S pellet (22.2 mg ENG) inserted into the inner aspect of the non-dominant upper arm.
干预措施: 22.2 mg Etonogestrel (ENG) (Drug)
Two Casea S pellets
In Part 2 of this study, sixteen women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm.
干预措施: 44.4 mg Etonogestrel (ENG) (Drug)
结局指标
主要结局
Maximum observed serum concentration (Cmax)
时间窗: 12 weeks; 52 weeks; 114 weeks
Maximum observed serum concentration (Cmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Time to Cmax (tmax)
时间窗: 12 weeks; 52 weeks; 114 weeks
Time to Cmax (tmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Geometric mean serum ENG concentration
时间窗: 28 days; 114 weeks
Geometric mean serum ENG concentration at treatment days 28 and 84
Area under concentration time curve (AUC 0-28)
时间窗: 28 days; 154 days; 364 days
Area under the concentration time curve through days 28 and day 84
Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546
时间窗: 52 weeks
pharmacokinetics of ENG after subdermal insertion of 2 Casea S pellets
Assessment of the removability of Casea S pellets
时间窗: up to 52 weeks
Number and descriptions of incidence of removal complications
Assessment Casea S pellets removability
时间窗: up to 52 weeks
Time of the procedure duration of procedure
Ability to completely remove the pellet and ease of removal
时间窗: up to 52 weeks
Physician's assessment of the removability of Casea S pellets qualified as "complete removal, partial removal, or not removed" on the study removal assessment.
Time to undetectable ENG levels
时间窗: 114 weeks
Apparent absorption half-life; Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546; Time above 90 pg/mL
次要结局
- Occurrence of treatment emergency adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions(up to 114 weeks)
- Assessment of the ease of insertion of Casea S pellets(up to 114 weeks)
- Assessment of the duration of Casea S pellets insertion(up to 114 weeks)
- Assessment of the complications of insertion of Casea S pellets(up to 114 weeks)
- Follicular and luteal activity following subdermal insertion of Casea S pellets(up to 114 weeks)
- Estimate of ENG release rates using explant analysis(up to 114 weeks)