Clinical trial NCT02777268: Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
Collaborators: name: Simbec Research
First posted: 2016-05-19
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone
timeFrame: -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
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone
timeFrame: -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
measure: Area Under the Curve (AUC0-t) of Infacort vs Hydrocortisone
timeFrame: -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 outcomes:
measure: Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
timeFrame: -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
measure: Time to Maximum Plasma Concentration (Tmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
timeFrame: -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
measure: Area Under the Curve (AUC0-t) of Infacort at Doses of 0.5, 2, 5 and 10 mg
timeFrame: 1 day
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by Medical Dictionary for Regulatory Activities (MedDRA) Dictionary, Version 16.0.
timeFrame: 1 day
Other outcomes:
Locations:
Study officials:
affiliation: Simbec Research
name: Girish Sharma, MD
role: PRINCIPAL_INVESTIGATOR
References: