Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Adults With Congenital Adrenal Hyperplasia
Condition: CAH - Congenital Adrenal Hyperplasia
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Hyperplasia
Intervention: NBI-74788
Intervention description: Capsule, administered daily.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be in good general health.

          2. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH.

          3. Be on a stable regimen of steroidal treatment for CAH that is expected to remain
             stable throughout the study.

          4. 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.

          5. Subjects of childbearing potential must have a negative pregnancy test at screening
             and negative urine pregnancy test at baseline.

          6. Have a negative urine drug (for illegal drugs) and alcohol breath test at screening
             and baseline.

          7. 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.

          8. Be willing to provide authorization for access to personal health information in
             conjunction with US Health Insurance Portability and Accountability Act (HIPAA).

        Exclusion Criteria:

          1. Have a clinically significant unstable medical condition or chronic disease, or
             malignancy.

          2. Had a medically significant illness within 30 days of screening.

          3. Have a known or suspected differential diagnosis of any of the other known forms of
             classic CAH.

          4. Have a history that includes bilateral adrenalectomy, hypopituitarism, or other
             condition requiring daily therapy with orally administered glucocorticoids.

          5. Are pregnant or lactating females.

          6. Have a history of epilepsy or serious head injury.

          7. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.

          8. Have hypersensitivity to any corticotropin releasing hormone antagonists.

          9. Test positive at screening for hepatitis B, hepatitis C, or human immunodeficiency
             virus (HIV), or have a history of a positive result.

         10. Have a recent history (≤1 year) of alcohol or drug abuse, or current evidence of
             substance dependence or abuse criteria.

         11. Used any anticoagulants or antiplatelet therapies within 30 days before screening.

         12. Have an active bleeding disorder.

         13. 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.

         14. Have a blood loss ≥550 mL or donated blood within 56 days or donated plasma within 7
             days before baseline.