Clinical trial NCT03525886: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Adults With Congenital Adrenal Hyperplasia
Official title: A Phase 2, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Adult Subjects With Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CAH - Congenital Adrenal Hyperplasia
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2018-05-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline to Day 14 in 17-hydroxyprogesterone (17-OHP) Morning Window Averages
timeFrame: Baseline and Day 14
Secondary outcomes:
measure: Percent Change From Baseline to Day 14 in Androstenedione Morning Window Averages
timeFrame: Baseline and Day 14
measure: Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) Morning Window Averages
timeFrame: Baseline and Day 14
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Neurocrine Clinical Site
state: Colorado
city: Indianapolis
country: United States
facility: Neurocrine Clinical Site
state: Indiana
city: Ann Arbor
country: United States
facility: Neurocrine Clinical Site
state: Michigan
city: Minneapolis
country: United States
facility: Neurocrine Clinical Site
state: Minnesota
city: Philadelphia
country: United States
facility: Neurocrine Clinical Site
state: Pennsylvania
city: Seattle
country: United States
facility: Neurocrine Clinical Site
state: Washington
Study officials:
affiliation: Neurocrine Biosciences
name: Clinical Development Lead
role: STUDY_DIRECTOR
References:
citation: 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.