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

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

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).

Study Overview

• Status: Completed
• Conditions: CAH - Congenital Adrenal Hyperplasia
• Intervention / Treatment: Drug: NBI-74788

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Neurocrine Clinical Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Neurocrine Clinical Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Neurocrine Clinical Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Neurocrine Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Neurocrine Clinical Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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 ≥250 mL or donated blood within 56 days or donated plasma within 7 days before baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBI-74788; NBI-74788 administered orally for 14 consecutive days.	Drug: NBI-74788; NBI-74788 administered orally for 14 consecutive days.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Publications and helpful links

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2019
• Primary Completion (Actual): July 2, 2021
• Study Completion (Actual): July 2, 2021

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: August 1, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction
• Other Study ID Numbers: NBI-74788-CAH2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No