Phase IV Study of the Pharmacokinetics and Safety of Ceftriaxone and Benzathine Penicillin G During Pregnancy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 15
- 主要终点
- Geometric mean AUC0-tau in the second trimester
研究概览
简要总结
IMPAACT 2044 is a study to characterize the pharmacokinetics (PK) and safety of ceftriaxone and benzathine penicillin G during pregnancy. Up to 78 pregnant women receiving (1) ceftriaxone for indications other than syphilis or (2) benzathine penicillin G for treatment of syphilis from non-study clinical care providers will be enrolled at study sites located in the United States. Approximately 22 infants of pregnant participants receiving benzathine penicillin G will also be enrolled.
详细描述
IMPAACT 2044 is a Phase IV, multi-site, open-label, non-randomized, opportunistic study to characterize the pharmacokinetics (PK) and safety of ceftriaxone and benzathine penicillin G during pregnancy.
The study includes two arms, with Arm 1 subdivided by route of administration:
Arm 1A: Intravenous (IV) ceftriaxone Arm 1B: Intramuscular (IM) ceftriaxone Arm 2: IM benzathine penicillin G
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Is of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with Institutional Review Board (IRB) policies and procedures and is willing and able to provide written informed consent for her own and, if applicable (Arm 2), her infant's study participation
- •At screening, has a viable singleton intrauterine pregnancy of any gestational age confirmed by fetal ultrasound, as determined by the site investigator based on medical records, with trimester documented based on the best available obstetric estimate
- •At screening, is receiving or expected to receive one of the following drugs under study as prescribed by a clinical care provider and documented in medical records:
- •Ceftriaxone: IV or IM administration for an indication other than syphilis
- •Benzathine penicillin G: IM administration for treatment of syphilis
- •At entry, expects to remain in the geographic area of the study site during pregnancy and at least 30 days postpartum
排除标准
- •Previously enrolled in this study
- •Requires desensitization to ceftriaxone or benzathine penicillin G as determined by the site investigator based on pregnant participant report and available medical records
- •Has any of the following as determined by the site investigator based on pregnant participant report and available medical records:
- •Current indication for hemodialysis
- •Current indication for intensive care unit hospitalization
- •Creatinine (Cr) ≥ 3.5 x upper limit of normal (ULN) at any time during the current pregnancy and/or chronic kidney disease Stage 5
- •Receipt of any of the following prohibited medications within seven days prior to entry as determined by the site investigator based on pregnant participant report and available medical records:
- •Probenecid
- •Penicillin
- •Arm 1A: any penicillin
- •Arm 1B: any penicillin
- •Arm 2: penicillin other than benzathine penicillin G
- •Benzapril
- •Chlorpropamide
- •Diflunisal
- •Irbesartan
- •Ketoprofen
- •Ketorolac tromethamine
- •Meclofenamic acid
- •Mefenamic acid
- •Oxaprozin
- •Parecoxib
- •Penciclovir
- •Pioglitazone
- •Telmisartan
- •Valsartan
- •Receipt of any investigational agent within seven days prior to entry as determined by the site investigator based on pregnant participant report and available medical records
- •Has any documented or suspected clinically significant condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
研究组 & 干预措施
Active comparator: Arm 1A: IV ceftriaxone
Intravenous ceftriaxone
干预措施: Ceftriaxon (Drug)
Active Comparator: Arm 1B: IM ceftriaxone
Intramuscular ceftriaxone
干预措施: Ceftriaxon (Drug)
Active Comparator: Arm 2: IM benzathine penicillin G
Intramuscular benzathine penicillin G
干预措施: Benzathine penicillin G (Drug)
结局指标
主要结局
Geometric mean AUC0-tau in the second trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean area under the curve (AUC) during the dosing interval (AUC0-tau) in the first trimester trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean terminal elimination half-life (t1/2) in the first trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean t1/2 in the second trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean trough concentration (Ctrough) in the first trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean AUC0-tau in the third trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean Ctrough in the second trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Geometric mean Ctrough in the third trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Median time to Cmax (Tmax) in the first trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Geometric mean t1/2 in the third trimester
时间窗: First on-study dose through 24 hours
Arm 1A
Median maximum plasma concentration during the dose interval (Cmax) in the first trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Median Cmax in the second trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Median Tmax in the second trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Median Cmax in the third trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Median Tmax in the third trimester
时间窗: First on-study dose through up to 24 hours
Arm 1B
Geometric mean AUC at 7 days (AUC 0-7d) in the first trimester
时间窗: First on-study dose through 7 days
Arm 2
Geometric mean AUC at 14 days (AUC0-14d) in the first trimester
时间窗: First on-study dose through 14 days
Arm 2
Geometric mean plasma concentration at 2 hours (C2h) in the first trimester
时间窗: 2 hours post-first on-study dose
Arm 2
Geometric mean plasma concentration at 24 hours (C24h) in the first trimester
时间窗: 24 hours post-first on-study dose
Arm 2
Geometric mean plasma concentration at 4 days (C4d) in the first trimester
时间窗: 4 days post-first on-study dose
Arm 2
Geometric mean plasma concentration at 7 days (C7d) in the first trimester
时间窗: 7 days post-first on-study dose
Arm 2
Geometric mean plasma concentration at 14 days (C14d) in the first trimester
时间窗: 14 days post-first on-study dose
Arm 2
Geometric mean AUC0-7d in the second trimester
时间窗: First on-study dose through 7 days
Arm 2
Geometric mean AUC0-14d in the second trimester
时间窗: First on-study dose through 14 days
Arm 2
Geometric mean C2h in the second trimester
时间窗: 2 hours post-first on-study dose
Arm 2 (as defined above)
Geometric mean C24h in the second trimester
时间窗: 24 hours post-first on-study dose
Arm 2 (as defined above)
Geometric mean C4d in the second trimester
时间窗: 4 days post-first on-study dose
Arm 2 (as defined above)
Geometric mean C7d in the second trimester
时间窗: 7 days post-first on-study dose
Arm 2 (as defined above)
Geometric mean C14d in the second trimester
时间窗: 14 days post-first on-study dose
Arm 2 (as defined above)
Geometric mean C2h in the third trimester
时间窗: 2 hours post-first on-study dose
Arm 2 (as defined above)
Geometric mean C14d in the third trimester
时间窗: 14 days post-first on-study dose
Arm 2 (as defined above)
Geometric mean AUC0-7d in the third trimester
时间窗: First on-study dose through 7 days
Arm 2
Geometric mean AUC0-14d in the third trimester
时间窗: First on-study dose through 14 days
Arm 2
Geometric mean C24h in the third trimester
时间窗: 24 hours post-first on-study dose
Arm 2 (as defined above)
Geometric mean C4d in the third trimester
时间窗: 4 days post-first on-study dose
Arm 2 (as defined above)
Geometric mean C7d in the third trimester
时间窗: 7 days post-first on-study dose
Arm 2 (as defined above)
次要结局
- Proportion of participants with a maternal serious adverse event (SAE)(First on-study dose through 7 days)
- Proportion of participants with a maternal SAE assessed as related to drug under study(First on-study dose through up to 28 days)
- Proportion of participants with a maternal SAE(First on-study dose through up to 28 days)
- Proportion of participants with a spontaneous abortion or miscarriage (<20 weeks gestation)(At pregnancy outcome/delivery/birth)
- Proportion of participants with a stillbirth (≥20 weeks gestation)(At pregnancy outcome/delivery/birth)
- Proportion of participants with an infant small for gestational age (SGA; weight <10th percentile for gestational age, adjusted for sex)(At pregnancy outcome/delivery/birth)
- Proportion of participants with a preterm birth (<37 weeks gestation)(At pregnancy outcome/delivery/birth)
- Proportion of participants with an infant congenital anomaly consistent with the definition of defect provided by Metropolitan Atlanta Congenital Defects Program (MACDP)(At pregnancy outcome/delivery/birth)
- Proportion of participants with a maternal SAE assessed as related to drug under study(First on-study dose through 7 days)