Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Pediatric Subjects With Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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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 approximately 12 pediatric female and male subjects (14 to 17 years of age) with a documented medical diagnosis of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH).

Official Title
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A Phase 2, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Pediatric Subjects With Congenital Adrenal Hyperplasia

Conditions
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CAH - Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: NBI-74788


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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 ≥250 mL or donated blood within 56 days or donated plasma within 7 days before baseline.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBI-74788<br>NBI-74788 administered orally for 14 consecutive days. | Drug: NBI-74788<br>* NBI-74788 administered orally for 14 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events following dosing of NBI-74788 |  | Up to 7 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of NBI-74788 and its metabolites following dosing of NBI-74788 |  | From baseline up to 7 weeks | 
| Concentrations of 17-hydroxyprogesterone (17-OHP) following dosing of NBI-74788 |  | From baseline up to 7 weeks | 
| Concentrations of biomarkers following dosing of NBI-74788 |  | From baseline up to 7 weeks |