A Single Centre, Open Label, Randomised, Crossover Study in Dexamethasone-suppressed Healthy Adult Male Volunteers to Compare the Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone Tablets at a Single Dose of 10 mg and to Evaluate the Dose Proportionality of Infacort® at Doses of 0.5 mg, 2 mg, 5 mg and 10 mg
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Diurnal Limited
- Enrollment
- 16
- Primary Endpoint
- Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone
Study Overview
Brief Summary
This was a single centre, open-label, randomised, 5-way crossover study.
Detailed Description
This was a single centre, open-label, randomised, 5-way crossover study design to compare the PK of Infacort® versus immediate-release hydrocortisone tablets and to evaluate the dose proportionality of 0.5 mg, 2 mg, 5 mg and 10 mg Infacort®. The study was conducted in 1 cohort of 16 healthy male subjects and comprised a Screening Visit, 5 treatment periods (Treatment Periods 1 to 5) and a Post-study Visit.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy male volunteers between 18 and 60 years of age, inclusive (at Screening Visit).
- •Subjects with a Body Mass Index (BMI) of 21-
- •Subjects with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 14 days prior to the first dose of investigational medicinal product (IMP).
- •Subjects with a negative urinary drugs of abuse screen determined within 14 days prior to the first dose of IMP. A positive alcohol test may have been repeated at the discretion of the Investigator.
- •Subjects with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
- •Subjects with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 14 days prior to the first dose of IMP.
- •Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements.
- •Subjects (unless anatomically sterile or where abstaining from sexual intercourse was in-line with the preferred and usual lifestyle of the subject) and sexual partners used effective contraception methods during the trial and for 3 months after the last dose of IMP, for example; oral contraceptive + condom, intra-uterine device (IUD) + condom or diaphragm with spermicide + condom.
- •Subjects were available to complete the study.
- •Subjects satisfied a medical examiner about their fitness to participate in the study.
- •Subjects provided written informed consent to participate in the study.
Exclusion Criteria
- •A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
- •Receipt of regular medication within 14 days prior to the first dose of IMP (including high dose vitamins, dietary supplements or herbal remedies).
- •Receipt of any vaccination within 14 days prior to the first dose of IMP.
- •Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
- •Presence of clinically significant 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.
- •A clinically significant history or family history of psychiatric disorders/illnesses.
- •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).
- •Participated in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. (N.B. The washout period between trials was defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
- •Subjects who had consumed more than 2 units of alcohol per day within 7 days prior to the first dose of IMP or had consumed any alcohol within the 48 hr period prior to the first dose of IMP.
- •Donation of 450 mL or more of blood within the previous 3 months.
- •Subjects who smoked (or ex-smokers who had smoked within 6 months prior to first dose of IMP).
- •Subjects who worked shifts (i.e. regularly alternated between days, afternoons and nights).
Arms & Interventions
Infacort 5 mg
Multi-particulate granules from 1 (5 mg) capsule
Intervention: Infacort (Drug)
Infacort 10 mg
Multi-particulate granules from 1 (10 mg) capsule
Intervention: Infacort (Drug)
Hydrocortisone
1 (10 mg) tablet
Intervention: Hydrocortisone (Drug)
Infacort 0.5 mg
Multi-particulate granules from 1 (0.5 mg) capsule
Intervention: Infacort (Drug)
Infacort 2 mg
Multi-particulate granules from 1 (2 mg) capsule
Intervention: Infacort (Drug)
Outcomes
Primary Outcomes
Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone
Time Frame: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Time to Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone
Time Frame: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
To compare the Tmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Area Under the Curve (AUC0-t) of Infacort vs Hydrocortisone
Time Frame: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
To compare the AUC0-t of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. AUC0-t represents the total exposure to drug over time, hence the reporting of a single value below.
Secondary Outcomes
- Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg(-1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h)
- Time to Maximum Plasma Concentration (Tmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg(-1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h)
- Area Under the Curve (AUC0-t) of Infacort at Doses of 0.5, 2, 5 and 10 mg(1 day)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by Medical Dictionary for Regulatory Activities (MedDRA) Dictionary, Version 16.0.(1 day)