A Study of Infacort® Versus Cortef® in Healthy Adult Male and Female Subjects

NCT03311932 | Completed Phase 1 FDA Drug

• 1 other identifier: Infacort 007
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This was a two-part, single centre, open-label, randomised, single dose, two-period, crossover study to evaluate the bioavailability of Infacort® versus Cortef® immediate release hydrocortisone tablets in dexamethasone-suppressed healthy adult male and female subjects in the fasted and fed states.

Conditions

Adrenal Insufficiency

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic parameters for serum cortisol - Maximum serum concentration (Cmax)

  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.

  Blood samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 and 12 hours; in both periods

• Pharmacokinetic parameters for serum cortisol - Area under the serum cortisol concentration-time curve (AUC0-t)

  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.

  Blood samples taken at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 5 , 6, 8, 10 and 12 hours; in both periods

• Pharmacokinetic parameters for serum cortisol - Area under the curve extrapolated to infinity (AUC0-inf)

  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.

  Blood samples taken at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 5 , 6, 8, 10 and 12 hours; in both periods

Secondary Outcomes (9)

• Adverse events (AEs)

  Through study completion - approximately 6 weeks

• Vital signs

  Through study completion - approximately 6 weeks

• Electrocardiogram (ECG)

  Through study completion - approximately 6 weeks

• Safety Laboratory Data

  Through study completion - approximately 6 weeks

• Pharmacokinetic parameters for serum cortisol - Time to maximum cortisol concentration (Tmax)

  Blood samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 and 12 hours; in both periods

Study Arms (4)

Cortef® Tablets - fasted

ACTIVE COMPARATOR

Single dose of 20mg Cortef® Tablets - fasted arm

Drug: Cortef®

Infacort® - fasted

EXPERIMENTAL

Single dose of 20mg Infacort® - fasted arm

Drug: Infacort®

Cortef® Tablets - fed

ACTIVE COMPARATOR

Single dose of 20mg Cortef® Tablets - fed arm

Drug: Cortef®

Infacort® - fed

EXPERIMENTAL

Single dose of 20mg Infacort® - fed arm

Drug: Infacort®

Interventions

Infacort® DRUG

Immediate release multiparticulate formulation (granules) of hydrocortisone

Infacort® - fasted; Infacort® - fed

Cortef® DRUG

Immediate release hydrocortisone tablets

Cortef® Tablets - fasted; Cortef® Tablets - fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females between 18 and 55 years of age, inclusive (at screening).
• A body mass index (BMI) of 18 to 30 kg/m2 (inclusive)
• No clinically significant abnormal serum biochemistry, haematology or urine examination values, as defined by the Investigator.
• A negative urinary drugs of abuse screen. A positive alcohol test or drugs of abuse test could be repeated at the discretion of the Investigator.
• Negative human immunodeficiency virus (HIV) and hepatitis B and C test results.
• No clinically significant abnormalities in the 12-lead ECG, as defined by the Investigator.
• No clinically significant deviation outside of the normal ranges for blood pressure and heart rate measurements, as defined by the Investigator.
• Male participants (unless anatomically sterile or abstinence from sexual intercourse was in line with preferred and usual lifestyle) and sexual partners were to use an effective contraception method during the study and for 3 months after the last intervention, for example:
• Established use of oral, injected or implanted hormonal contraceptive.
• Intrauterine device or intrauterine system.
• Condom and diaphragm with spermicide.
• Female participants of childbearing potential (unless abstinence from sexual intercourse was in line with preferred and usual lifestyle) with a negative pregnancy test at screening and on admission, and willing to use an effective method of contraception from the first dose until 3 months after the last intervention, for example:
• Established use of oral / injected / implanted hormonal methods of contraception.
• Intrauterine device or intrauterine system.
• Barrier methods: condom + occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
• Receipt of any medication other than acetaminophen within the 14 days prior to dosing (including topical steroids, vitamins, dietary supplements or herbal remedies).
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• Receipt of any vaccination within the previous one month.
• Presence of infections (systemic fungal and viral infections, acute bacterial infections).
• Current or previous history of tuberculosis.
• A clinically significant history of previous allergy/sensitivity to hydrocortisone and/or dexamethasone.
• Meeting any of the contraindications for Cortef® and/or dexamethasone, as detailed in the USPI and Summary of Product Characteristics (SmPC).
• A clinically significant history of drug or alcohol abuse.
• Inability to communicate well with the Investigator (i.e. language problem, poor mental development or impaired cerebral function).
• Participation in a New Chemical Entity or marketed drug clinical study within the previous 3 months or, five half-lives of study drug, whichever is the longer period. (NB. the three-month washout period between trials is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
• Participants who had consumed more than 2 units of alcohol per day within the 7 days prior to the first dose or had consumed any alcohol within the 48-hour period prior to the first dose.
• Donation or receipt of equal to or greater than 450 mL of blood within the previous three months.
• Participants who smoked (or ex-smokers who had smoked within the 6 months prior to the first dose). This included e-cigarette and shisha users.
• Participants who worked shifts (i.e. regularly alternated between days, afternoons and nights).

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• Simbec Research: collaborator
• Brush Clinical Research Ltd.: collaborator
• Voet Consulting: collaborator
• Bionical-Emas Pharma Ltd: collaborator
• Medical Matters International Ltd: collaborator
• Nichol Pharma Services Ltd.: collaborator

Study Sites (1)

Simbec Research Ltd.

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Adrenal Insufficiency

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• A Koch

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: October 17, 2017
• Study Start: April 16, 2018
• Primary Completion: July 13, 2018
• Study Completion: July 13, 2018
• Last Updated: October 29, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)