Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Infacort
Hydrocortisone granules · 5 trials · 1 indication
The primary endpoint was the nature and occurrence of serious adverse events (SAEs) and adverse events (AEs) observed throughout the study. AEs were recorded from the time of the first intake of Infacort until the final visit.
The primary endpoint will be the maximum levels of serum cortisol concentration up to 240 minutes after intake of study drug as determined by the central laboratory.
Comparing the maximum serum cortisol concentration (Cmax) of Infacort® compared to Cortef® immediate release hydrocortisone tablets.This PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.
Comparing the total drug exposure over time for Infacort® compared to Cortef®. This PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.
Comparing the total drug exposure over time for Infacort® compared to Cortef® extrapolated to infinity from dosing time, based on the last observed concentration. This This PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.
The pharmacokinetic parameter AUC0-inf of Infacort® administered as sprinkles with yoghurt and soft food compared to Infacort® administered as dry granules to the back of the tongue.
The pharmacokinetic parameter AUC0-inf of Infacort® administered as sprinkles with yoghurt and soft food compared to Infacort® administered as dry granules to the back of the tongue.
The pharmacokinetic parameter Cmax of Infacort® administered as sprinkles with yoghurt and soft food compared to Infacort® administered as dry granules to the back of the tongue.
Derived PK for Serum Cortisol: Maximum serum concentration (Cmax)
Derived PK for Serum Cortisol: Area under the curve from 0-24 hours
| Arm | Type | Description |
|---|---|---|
| Infacort | EXPERIMENTAL | Infacort® granules |
| Cortef® Tablets - fasted | ACTIVE_COMPARATOR | Single dose of 20mg Cortef® Tablets - fasted arm |
| Infacort® - fasted | EXPERIMENTAL | Single dose of 20mg Infacort® - fasted arm |
| Cortef® Tablets - fed | ACTIVE_COMPARATOR | Single dose of 20mg Cortef® Tablets - fed arm |
| Infacort® - fed | EXPERIMENTAL | Single dose of 20mg Infacort® - fed arm |
| Infacort - Yoghurt | EXPERIMENTAL | One single 5mg dose of Infacort will be sprinkled onto 5mL of yoghurt and swallowed within three minutes. This will be taken with 240mL of water. |
| Infacort - Soft Food | EXPERIMENTAL | One single 5mg dose of Infacort will be sprinkled onto 5mL of soft food (such as applesauce) and swallowed within three minutes. This will be taken with 240mL of water. |
| Infacort - Dry Granules | ACTIVE_COMPARATOR | One single 5mg dose of Infacort will be administered as dry granules to the back of the tongue and swallowed. This will be taken with 240mL of water. |
| Endogenous Cortisol | NO_INTERVENTION | No Study medication will be given during this study period, however various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. |
| Dexamethasone | OTHER | 1mg Dexamethasone will be administered at 22:00 on Day 1 and at 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. Dexamethasone is considered a challenge agent and therefore a non-IMP |
| Infacort® | EXPERIMENTAL | 20mg Infacort® will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous adrenocorticotropic Hormone (ACTH) and cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. |
| Hydrocortisone Tablet | ACTIVE_COMPARATOR | 20mg Hydrocortisone Tablet will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous ACTH and Cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. |
| i.v Hydrocortisone Injection | ACTIVE_COMPARATOR | 20mg i.v. Hydrocortisone Injection will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous ACTH and Cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. |
| Name | Type | Description |
|---|---|---|
| Infacort® | DRUG | Infacort® is a dry granule formulation of hydrocortisone stored in capsules available in different strengths (0.5, 1.0, 2.0 and 5.0 mg). |
| Cortef® | DRUG | Immediate release hydrocortisone tablets |
| Infacort | DRUG | Immediate-release multiparticulate formulation of hydrocortisone. |
| Hydrocortisone granules | DRUG | Multi-particulate granules |
| Hydrocortisone Tablet | DRUG | Standard hydrocortisone tablets |
| i.v. Hydrocortisone Injection | DRUG | Standard hydrocortisone solution for intravenous injection |
| Dexamethasone | OTHER | Challenge agent |
Inclusion Criteria: Subjects successfully completing study Infacort 003, whose inclusion criteria were: 1. Male and female children less than 6 years of age. 2. A diagnosis of adrenal insufficiency (AI) as confirmed by an inappropriately low cortisol usually with other supporting tests. 3. Receivi...
Hydrocortisone granules are being developed for adrenal insufficiency, a condition in which the adrenal glands do not produce enough cortisol. The formulation is an oral small molecule studied in a Phase 1 trial in healthy adult male volunteers in the United Kingdom.
Hydrocortisone granules target NR3C1, the glucocorticoid receptor. The drug acts as an agonist at this receptor, meaning it activates the receptor to mimic the effects of naturally occurring cortisol. This mechanism underlies its development for adrenal insufficiency.
Hydrocortisone granules are being developed by Neurocrine Biosciences, Inc., which trades on the Nasdaq under the ticker NBIX. The company is responsible for the clinical development program for this adrenal insufficiency candidate.
Hydrocortisone granules are in Phase 1 clinical development. The program has completed one Phase 1 trial and has no active trials at this time. The drug is investigational and has not been approved by the FDA for any indication.
One completed Phase 1 trial, NCT01960530, evaluated hydrocortisone granules. The study enrolled 14 healthy adult male volunteers in the United Kingdom and was active-controlled and randomized. It was titled "An Investigational Study of Hydrocortisone" and focused on adrenal insufficiency.