A Phase 1, Open-Label, Single-Dose, Sequential Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-77860 in Adolescent Females With Congenital Adrenal Hyperplasia
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Number of participants with adverse events following one oral dose of NBI-77860
研究概览
简要总结
This is a Phase 1, multicenter, open-label, single-dose study to evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NBI-77860 in subjects with congenital adrenal hyperplasia (CAH). The study will be conducted in approximately 15 adolescent females (12-18 years of age) with a documented medical diagnosis of classic 21-hydroxylase deficiency CAH. The study will include three independent dose cohorts of NBI-77860 (approximately 5 subjects per dose cohort). Ascending doses will be evaluated as part of a sequential-cohort design.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Have documentation of written informed consent, or written and witnessed assent from the subject and written informed consent from the subject's parent or legal guardian.
- •Be in good general health.
- •Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH.
- •Be on a stable regimen of steroidal treatment for CAH for a minimum of 30 days before baseline (Night 1) that is expected to remain stable throughout the study.
- •Subjects of childbearing potential must be instructed on the proper use of barrier methods of contraception and agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently from screening until the final study visit or 30 days after the last dose of study drug, whichever is longer.
- •Subjects of childbearing potential must have a negative pregnancy test at screening and negative urine pregnancy test at baseline (Night 1).
- •Have a negative urine drug (for illegal drugs) and alcohol breath test at screening and baseline (Night 1).
- •Be willing and able to adhere to the study regimen and study procedures described in the protocol and informed consent/assent form, including all requirements at the study center and return for the follow-up visit.
- •Be willing to provide authorization for access to personal health information in conjunction with US Health Insurance Portability and Accountability Act (HIPAA).
排除标准
- •Have a clinically significant unstable medical condition or chronic disease, or malignancy.
- •Had a medically significant illness within 30 days of screening.
- •Have a known or suspected differential diagnosis of any of the other known forms of classic CAH.
- •Have a history that includes bilateral adrenalectomy, hypopituitarism, or other condition requiring daily therapy with orally administered glucocorticoids.
- •Pregnant or lactating females.
- •Have a history of epilepsy or serious head injury.
- •Test positive at screening for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), or have a history of a positive result.
- •Have a recent history (≤1 year) of alcohol or drug abuse, or current evidence of substance dependence or abuse criteria.
- •Used any other investigational drug within 30 days before initial screening, or plans to use an investigational drug (other than the study drug) during the study.
- •Have a blood loss ≥250 mL or donated blood within 56 days or donated plasma within 7 days before baseline.
- •Self-report consumption of more than 6 caffeine-containing beverages a day within the last month before baseline.
研究组 & 干预措施
NBI-77860 Dose Group1
NBI-77860 administered orally on Night 1 at bedtime (at approximately 2200 hours).
干预措施: NBI-77860 (Drug)
NBI-77860 Dose Group 2
NBI-77860 administered orally on Night 1 at bedtime (at approximately 2200 hours). Dosing will not commence until all safety and PK results from the dose group 1 have been reviewed to ensure there are no safety concerns and that maximum tolerated dose (MTD) has not been reached.
干预措施: NBI-77860 (Drug)
NBI-77860 Dose Group 3
NBI-77860 administered orally on Night 1 at bedtime (at approximately 2200 hours). Dosing will not commence until all safety and PK results from the dose group 2 have been reviewed to ensure there are no safety concerns and that maximum tolerated dose (MTD) has not been reached.
干预措施: NBI-77860 (Drug)
结局指标
主要结局
Number of participants with adverse events following one oral dose of NBI-77860
时间窗: Up to 8 weeks
次要结局
- Concentrations of 17-hydroxyprogesterone (17-OHP) following one oral dose of NBI-77860(Screening, Night 1, Day 2 (10, 12 and 24 hours postdose) and 35 (or early termination))
- Concentrations of adrenocorticotropin hormone (ACTH) following one oral dose of NBI-77860(Screening, Night 1, Day 2 (10, 12 and 24 hours postdose) and 35 (or early termination))
- Area Under Concentration Curve (AUC) of NBI-77860 and its metabolites following one oral dose of NBI-77860(Night 1 and Days 2, 7, 14, 21 and 35 (or early termination))