Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone

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

This was a single centre, open-label, randomised, 5-way crossover study.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Infacort; Drug: Hydrocortisone

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers between 18 and 60 years of age, inclusive (at Screening Visit).
• Subjects with a Body Mass Index (BMI) of 21-28.
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infacort 0.5 mg; Multi-particulate granules from 1 (0.5 mg) capsule	Drug: Infacort; Multi-particulate granules
Experimental: Infacort 2 mg; Multi-particulate granules from 1 (2 mg) capsule	Drug: Infacort; Multi-particulate granules
Experimental: Infacort 5 mg; Multi-particulate granules from 1 (5 mg) capsule	Drug: Infacort; Multi-particulate granules
Experimental: Infacort 10 mg; Multi-particulate granules from 1 (10 mg) capsule	Drug: Infacort; Multi-particulate granules
Active Comparator: Hydrocortisone; 1 (10 mg) tablet	Drug: Hydrocortisone; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone	To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 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 Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone	To compare the Tmax of Infacort® versus immediate-release hydrocortisone in a single dose of 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 vs Hydrocortisone	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.	-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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg	To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg 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	To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg 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	To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg 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.	To assess the safety and tolerability of Infacort® throughout the study. For a full list of TEAEs per arm, please refer to the Adverse Events section.	1 day

Collaborators and Investigators

• Sponsor: Diurnal Limited
• Collaborators: Simbec Research
• Investigators: Principal Investigator: Girish Sharma, MD, Simbec Research

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: April 27, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: Infacort 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO