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

NCT03525886 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NBI-74788-CAH2001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

CAH - Congenital Adrenal Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Day 14 in 17-hydroxyprogesterone (17-OHP) Morning Window Averages

  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.

  Baseline and Day 14

Secondary Outcomes (2)

• 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

Study Arms (4)

Cohort 1 (50 mg QHS)

EXPERIMENTAL

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

Drug: NBI-74788

Cohort 2 (100 mg QHS)

EXPERIMENTAL

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

Drug: NBI-74788

Cohort 3 (100 mg QPM)

EXPERIMENTAL

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

Drug: NBI-74788

Cohort 4 (100 mg BID)

EXPERIMENTAL

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

Drug: NBI-74788

Interventions

NBI-74788 DRUG

Capsule, administered daily.

Cohort 1 (50 mg QHS); Cohort 2 (100 mg QHS); Cohort 3 (100 mg QPM); Cohort 4 (100 mg BID)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (6)

Neurocrine Clinical Site

Aurora, Colorado, 80045, United States

Location

Neurocrine Clinical Site

Indianapolis, Indiana, 46202, United States

Location

Neurocrine Clinical Site

Ann Arbor, Michigan, 48109, United States

Location

Neurocrine Clinical Site

Minneapolis, Minnesota, 55454, United States

Location

Neurocrine Clinical Site

Philadelphia, Pennsylvania, 19104, United States

Location

Neurocrine Clinical Site

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Auchus RJ, Sarafoglou K, Fechner PY, Vogiatzi MG, Imel EA, Davis SM, Giri N, Sturgeon J, Roberts E, Chan JL, Farber RH. Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2022 Feb 17;107(3):801-812. doi: 10.1210/clinem/dgab749.

  PMID: 34653252 BACKGROUND

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Interventions

crinecerfont

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Study Officials

• Clinical Development Lead

  Neurocrine Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 16, 2018
• Study Start: April 10, 2018
• Primary Completion: April 7, 2020
• Study Completion: April 7, 2020
• Last Updated: May 3, 2022
• Results First Posted: May 3, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)