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

CAH - Congenital Adrenal Hyperplasia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03525886
• Other study ID #: NBI-74788-CAH2001
• Status: Completed
• Phase: Phase 2
• Start date: April 10, 2018
• Est. completion date: April 7, 2020

Study information

• Verified date: April 2022
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 7, 2020
• Est. primary completion date: April 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adrenal Hyperplasia, Congenital
• Adrenocortical Hyperfunction
• Adrenogenital Syndrome
• CAH - Congenital Adrenal Hyperplasia
• Hyperplasia

Intervention

Drug:
• NBI-74788
Capsule, administered daily.

Locations

Country	Name	City	State
United States	Neurocrine Clinical Site	Ann Arbor	Michigan
United States	Neurocrine Clinical Site	Aurora	Colorado
United States	Neurocrine Clinical Site	Indianapolis	Indiana
United States	Neurocrine Clinical Site	Minneapolis	Minnesota
United States	Neurocrine Clinical Site	Philadelphia	Pennsylvania
United States	Neurocrine Clinical Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Neurocrine Biosciences

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change From Baseline to Day 14 in Androstenedione Morning Window Averages	Percent changes in androstenedione were assessed through the collection of samples from 0600 hours to 1000 hours prior to study drug administration (baseline) and after 14 days of study drug dosing. The 3 samples collected at each visit during this morning window were averaged and used to determine the change and percent change from baseline.	Baseline and Day 14
Secondary	Percent Change From Baseline to Day 14 in Adrenocorticotropic Hormone (ACTH) Morning Window Averages	Percent changes in ACTH were assessed through the collection of samples from 0600 hours to 1000 hours prior to study drug administration (baseline) and after 14 days of study drug dosing. The 3 samples collected at each visit during this morning window were averaged and used to determine the change and percent change from baseline.	Baseline and Day 14

External Links

•   Study website