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

Neurocrine Biosciences

Status and phase: Completed; Phase 2

Conditions: CAH - Congenital Adrenal Hyperplasia

Treatments: Drug: NBI-74788

Study type: Interventional

Funder types: Industry

Identifiers

NCT03525886

NBI-74788-CAH2001

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

Cohort 1 (50 mg QHS)

Experimental group

Description:

NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days.

Treatment:

Drug: NBI-74788

Cohort 2 (100 mg QHS)

Experimental group

Description:

NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days.

Treatment:

Drug: NBI-74788

Cohort 3 (100 mg QPM)

Experimental group

Description:

NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days.

Treatment:

Drug: NBI-74788

Cohort 4 (100 mg BID)

Experimental group

Description:

NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days.

Treatment:

Drug: NBI-74788