Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (50 mg QHS) | Experimental | NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
|
| Cohort 2 (100 mg QHS) | Experimental | NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
|
| Cohort 3 (100 mg QPM) | Experimental | NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days. |
|
| Cohort 4 (100 mg BID) | Experimental | NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NBI-74788 | Drug | Capsule, administered daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Lead | Neurocrine Biosciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neurocrine Clinical Site | Aurora | Colorado | 80045 | United States | ||
| Neurocrine Clinical Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34653252 | Background | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The study followed a sequential cohort design with four NBI-74788 dosing regimens, each administered for 14 consecutive days. There was ~2-week period to evaluate safety and tolerability data before proceeding from Cohort 1 to Cohort 2. Subjects who previously completed the study in Cohort 1 or 2 (and had no safety concerns) could reenroll into Cohorts 3 and/or 4 (in addition to new subjects); 18 unique subjects participated. First subject enrolled: 4/10/2018; Last subject completed: 4/7/2020
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (50 mg QHS) | NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
| FG001 | Cohort 2 (100 mg QHS) | NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Cohort 1 (50 mg QHS) |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 14, 2019 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Baseline and Day 14 |
| 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 |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| Neurocrine Clinical Site | Ann Arbor | Michigan | 48109 | United States |
| Neurocrine Clinical Site | Minneapolis | Minnesota | 55454 | United States |
| Neurocrine Clinical Site | Philadelphia | Pennsylvania | 19104 | United States |
| Neurocrine Clinical Site | Seattle | Washington | 98105 | United States |
| FG002 | Cohort 3 (100 mg QPM) | NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days. |
| FG003 | Cohort 4 (100 mg BID) | NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Cohort 2 (100 mg QHS) |
|
| Cohort 3 (100 mg QPM) |
|
| Cohort 4 (100 mg BID) |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 (50 mg QHS) | NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
| BG001 | Cohort 2 (100 mg QHS) | NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. |
| BG002 | Cohort 3 (100 mg QPM) | NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days. |
| BG003 | Cohort 4 (100 mg BID) | NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | A total of 18 unique subjects participated in the study. Subjects could participate in more than one cohort; Cohort 3 included 8 subjects and Cohort 4 included 5 subjects who had participated in other cohorts. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | A total of 18 unique subjects participated in the study. Subjects could participate in more than one cohort; Cohort 3 included 8 subjects and Cohort 4 included 5 subjects who had participated in other cohorts. | Count of Participants | Participants |
| ||||||||||
| Ethnicity (NIH/OMB) | A total of 18 unique subjects participated in the study. Subjects could participate in more than one cohort; Cohort 3 included 8 subjects and Cohort 4 included 5 subjects who had participated in other cohorts. | Count of Participants | Participants |
| ||||||||||
| Race (NIH/OMB) | A total of 18 unique subjects participated in the study. Subjects could participate in more than one cohort; Cohort 3 included 8 subjects and Cohort 4 included 5 subjects who had participated in other cohorts. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Pharmacodynamic (PD) analysis set, which includes all enrolled participants who received at least one dose of study drug and have at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit. | Posted | Median | Inter-Quartile Range | Percent (%) | 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. | Pharmacodynamic (PD) analysis set, which includes all enrolled participants who received at least one dose of study drug and have at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit. | Posted | Median | Inter-Quartile Range | Percent (%) | 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. | Pharmacodynamic analysis set, which includes all enrolled participants who received at least one dose of study drug and have at least one PD parameter measurement at baseline and at least one PD parameter measurement at the Day 14 visit. | Posted | Median | Inter-Quartile Range | Percent (%) | Baseline and Day 14 |
|
Up to 7 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 (50 mg QHS) | NBI-74788 50 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. | 0 | 8 | 0 | 8 | 7 | 8 |
| EG001 | Cohort 2 (100 mg QHS) | NBI-74788 100 mg once daily at bedtime (QHS) administered orally for 14 consecutive days. | 0 | 7 | 1 | 7 | 5 | 7 |
| EG002 | Cohort 3 (100 mg QPM) | NBI-74788 100 mg once daily in the evening (QPM) administered orally for 14 consecutive days. | 0 | 8 | 0 | 8 | 5 | 8 |
| EG003 | Cohort 4 (100 mg BID) | NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. | 0 | 8 | 0 | 8 | 5 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | MedDRA version 23.0 | Systematic Assessment | Single event of cholelithiasis, occurring 34 days after the last dose of study drug, assessed by the investigator as moderate in intensity and unlikely to be related to treatment. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Feeling abnormal | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA version 23.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA version 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA version 23.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Muscle fatigue | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Panic attack | Psychiatric disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Ovulation pain | Reproductive system and breast disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA version 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 23.0 | Systematic Assessment |
|
Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neurocrine Medical Information | Neurocrine Biosciences | 877-641-3461 | medinfo@neurocrine.com |
| Feb 25, 2022 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000312 | Adrenal Hyperplasia, Congenital |
| ID | Term |
|---|---|
| D047808 | Adrenogenital Syndrome |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000723083 | crinecerfont |
Not provided
Not provided
Not provided
|
| Cohort 2 (100 mg QHS) |
|
|
| Cohort 3 (100 mg QPM) |
|
|
| Cohort 4 (100 mg BID) |
|
|
|
| Cohort 2 (100 mg QHS) |
|
|
| Cohort 3 (100 mg QPM) |
|
|
| Cohort 4 (100 mg BID) |
|
|
|
| Cohort 2 (100 mg QHS) |
|
|
| Cohort 3 (100 mg QPM) |
|
|
| Cohort 4 (100 mg BID) |
|
|
|
| Cohort 2 (100 mg QHS) |
|
|
| Cohort 3 (100 mg QPM) |
|
|
| Cohort 4 (100 mg BID) |
|
|
| OG003 |
| Cohort 4 (100 mg BID) |
NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. |
|
|
| OG003 |
| Cohort 4 (100 mg BID) |
NBI-74788 100 mg twice daily (BID) administered orally for 14 consecutive days. |
|
|
| Unknown or Not Reported |
|
| Unknown or Not Reported |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|