An Open-label, Randomized, 2-Period, Crossover Study to Assess the Comparative Pharmacokinetics of LSP-5415 and NuvaRing® in Healthy Adult Females
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration-time curve from time zero to 28 days post dose (AUC0-28d) for ENG.
研究概览
简要总结
Lupin is developing LSP-5415, a contraceptive vaginal ring (CVR) containing 9 mg etonogestrel (ENG) and 1 mg ethinyl estradiol (EE), which releases an average of 0.12 mg/day of ENG and 0.010 mg/day of EE, intended for continual contraceptive delivery over 26 days followed by a 2-day, ring-free interval within a 28-day menstrual cycle.
LSP-5415 is intended to be similar to NuvaRing (a polymeric vaginal ring containing 11.7 mg ENG and 2.7 mg EE, which releases an average of 0.12 mg/day of ENG and 0.015 mg/day of EE for 21-day duration of activity and 7 day ring free interval) based on dosage form and ENG dose.
LSP-5415 is a vaginal ring with a lower dose of EE and a longer treatment duration (26 days and a 2 day ring free interval) than available in currently approved vaginal rings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 40.00 Year(s)（—）
- 性别
- Female
入选标准
- •Must be able, and willing, to sign Informed Consent Form prior to study participation in accordance with legal requirements.
- •Females (18 to 40 years of age, inclusive) without uncontrolled concomitant disease at Baseline Visit.
- •Have a regular menstrual cycle that is 24-32 days in duration.
- •Body Mass Index (BMI) of 18 kg/m2 to 30 kg/m
- •Will not be at risk for pregnancy, subjects must agree to consistently use reliable non-hormonal contraceptive methods (spermicide-coated condoms, male partner’s sterilization via vasectomy, or sexual abstinence), or be in a same-sex relationship from screening through study completion, or be surgically sterilized by bilateral tubal ligation.
- •Subjects must be in good physical and mental health as determined by vital signs, medical history.
- •Subjects must have a Blood Pressure reading in a sitting position, between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic) and pulse rate between 50 and 100 bpm.
- •Be at least 3 months after a delivery or abortion.
- •Willing to abstain from vaginal products e.g., tampons, intravaginal medications etc.
- •during the ring wear period for the study duration except water based vaginal lubricants/spermicides.
排除标准
- •Pregnancy, a positive serum ß-hCG pregnancy test at screening or lactation.
- •Use of tobacco- or nicotine-containing products within 6 months prior to check-in on Day
- •history of cervical carcinoma or other carcinomas of the vagina or vulva.
- •history of breast cancer or any hormonally sensitive cancer.
- •Subjects with abnormal pap smears that require colposcopic evaluations as defined by the fourth American Society of Colposcopy and Cervical Pathology sponsored guidelines for management of cervical cancer abnormalities during the next 6 months are excluded until they have undergone colposcopic evaluation which has determined that a cervical procedure is not necessary during the 6 months following the colposcopy.
- •History of thrombophlebitis, venous or arterial thromboembolic diseases.
- •Any known severe neurological, gastrointestinal, hepatic or other disease that might interfere with the intake of an investigational drug or any study condition.
- •Clinically relevant findings from serum biochemistry and hematology and HBsAg and C Virus/HIV serology.
- •Clinically relevant/significant ECG findings.
- •Additional contraindications related to the use of ethinyl estradiol (EE), or hormonal contraceptives including women with a high risk of arterial or venous thrombotic diseases.
- •Have cerebrovascular disease, coronary artery disease, thrombogenic valvular or thrombogenic rhythm diseases of the heart, inherited or acquired hypercoagulopathies, uncontrolled hypertension, diabetes mellitus with vascular disease, headaches with focal neurological symptoms or migraine headaches with aura
- •History of migraine with focal neurological symptoms.
- •Known hereditary or acquired predisposition for venous and or arterial thromboembolism.
- •Less than 2 weeks remobilization after major surgery or prolonged immobilization
- •Alcohol, drug, or medicine abuse, or suspicion thereof.
- •Use of long acting injectable or implant hormonal therapy.
- •A washout period of 10 months and two regular cycles is required for long-acting injectable contraceptive therapy or implant hormonal therapy prior to the start of screening.
- •Participation in another clinical trial at same time or within the preceding three months
- •Not fulfilling study specific requirements at screening.
- •Undiagnosed vaginal discharge/bleeding, vaginal lesions/ abnormalities or undiagnosed abnormal uterine bleeding.
- •Subjects suspected of having a vaginal infection may be enrolled after treatment and subsequent negative test results; partner treatment is also recommended.
- •any drugs that might interfere with the investigational drug.
- •any hormonal preparation 30 days prior to the start of screening.
- •any drugs known to induce liver enzymes.
- •any broad-spectrum antibiotics.
- •use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations.
结局指标
主要结局
Area under the plasma concentration-time curve from time zero to 28 days post dose (AUC0-28d) for ENG.
时间窗: 0, 1, 2, 4, 8, 12 hrs on Day 1, 2 (24 hrs), 3 (48 hrs), 5 (96 hrs), 7 (144 hrs), 9 (192 hrs), 12 (264 hrs), 14 (312 hrs), 18 (408 hrs), 21 (480 hrs), 24 (552 hrs), 26 (600 hrs), 28 (648 hrs), 29 (672 hrs, immediately before ring removal), Day 29 (1, 2, 4, 8, 12 hrs postremoval), Day 30 (24 hours post-removal), Day 31 (48 hrs post-removal) Day 32 (72 hrs post-removal), Day 33 (96 hours post-removal), Day 34 (120 post-removal hours), Day 35 (144 hrs post-removal), Day 36 (168 hrs post-removal)
From time zero to infinity (AUC0-inf) for ENG maximum observed plasma concentration (Cmax) for ENG
时间窗: 0, 1, 2, 4, 8, 12 hrs on Day 1, 2 (24 hrs), 3 (48 hrs), 5 (96 hrs), 7 (144 hrs), 9 (192 hrs), 12 (264 hrs), 14 (312 hrs), 18 (408 hrs), 21 (480 hrs), 24 (552 hrs), 26 (600 hrs), 28 (648 hrs), 29 (672 hrs, immediately before ring removal), Day 29 (1, 2, 4, 8, 12 hrs postremoval), Day 30 (24 hours post-removal), Day 31 (48 hrs post-removal) Day 32 (72 hrs post-removal), Day 33 (96 hours post-removal), Day 34 (120 post-removal hours), Day 35 (144 hrs post-removal), Day 36 (168 hrs post-removal)
From time zero to the last measurable concentration (AUC0-last) for ENG
时间窗: 0, 1, 2, 4, 8, 12 hrs on Day 1, 2 (24 hrs), 3 (48 hrs), 5 (96 hrs), 7 (144 hrs), 9 (192 hrs), 12 (264 hrs), 14 (312 hrs), 18 (408 hrs), 21 (480 hrs), 24 (552 hrs), 26 (600 hrs), 28 (648 hrs), 29 (672 hrs, immediately before ring removal), Day 29 (1, 2, 4, 8, 12 hrs postremoval), Day 30 (24 hours post-removal), Day 31 (48 hrs post-removal) Day 32 (72 hrs post-removal), Day 33 (96 hours post-removal), Day 34 (120 post-removal hours), Day 35 (144 hrs post-removal), Day 36 (168 hrs post-removal)
次要结局
- time to maximum observed plasma concentration (tmax) for ENG(Area under the plasma concentration-time curve from time zero to 21 days (AUC0-21d))