A Phase 2, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Adult Subjects With Congenital Adrenal Hyperplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline to Day 14 in 17-hydroxyprogesterone (17-OHP) Morning Window Averages
研究概览
简要总结
This is a Phase 2, open-label, multiple-dose, dose-escalation study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NBI-74788 in up to 30 adult female and male subjects (18 to 50 years of age) with a documented medical diagnosis of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH). The study will include a sequential-cohort design with four NBI-74788 dosing regimens, with each regimen administered for 14 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 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 a prespecified window 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.
- •Have a negative urine drug (for illegal drugs) and alcohol breath test at screening and baseline.
- •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.
- •Are pregnant or lactating females.
- •Have a history of epilepsy or serious head injury.
- •Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
- •Have hypersensitivity to any corticotropin releasing hormone antagonists.
- •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 anticoagulants or antiplatelet therapies within 30 days before screening.
- •Have an active bleeding disorder.
- •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 ≥550 mL or donated blood within 56 days or donated plasma within 7 days before baseline.
研究组 & 干预措施
Cohort 1 (50 mg QHS)
NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days.
干预措施: NBI-74788 (Drug)
Cohort 2 (100 mg QHS)
NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days.
干预措施: NBI-74788 (Drug)
Cohort 3 (100 mg QPM)
NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days.
干预措施: NBI-74788 (Drug)
Cohort 4 (100 mg BID)
NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days.
干预措施: NBI-74788 (Drug)
结局指标
主要结局
Percent Change From Baseline to Day 14 in 17-hydroxyprogesterone (17-OHP) Morning Window Averages
时间窗: Baseline and Day 14
Percent changes in 17-OHP were assessed through the collection of samples from 0600 hours to 1000 hours both prior to study drug administration (i.e., at baseline) and after 14 days of study drug dosing. The 3 samples collected during this morning window at each visit were averaged and used to determine the percent change from baseline.
次要结局
- Percent Change From Baseline to Day 14 in Androstenedione Morning Window Averages(Baseline and Day 14)
- Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) Morning Window Averages(Baseline and Day 14)