A Two-part Open Label, Randomised, Single Dose, Crossover Study in Healthy Volunteers to: (Part A) Compare the Pharmacokinetics of up to 6 Chronocort® Formulations, and (Part B) Determine the Dose Proportionality of a Selected Chronocort® Formulation at Three Dose Levels With an Additional Comparison With the Selected Formulation Dosed on Two Occasions Over a 24 Hour Period
Overview
- Phase
- Phase 1
- Intervention
- Chronocort
- Conditions
- Adrenal Insufficiency
- Sponsor
- Diurnal Limited
- Enrollment
- 28
- Primary Endpoint
- To compare the Tmax of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period. Parts A1 & A2 only
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This was an open label, randomised, single dose study, comprising Part A (undertaken in two separate three-period crossover cohorts denoted as A1 and A2) and Part B (undertaken in one four-period crossover cohort), to evaluate the PK of Chronocort® in healthy male volunteers. The washout interval in both Part A and Part B was 1-week in between each treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male volunteers between 18 and 60 years of age, inclusive (at screening).
- •Subjects with a Body Mass Index (BMI) of 21-
- •Body Mass Index = Body weight (kg) / (Height (m))
- •Subjects with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 14 days prior to the first dose.
- •Subjects with negative urinary drugs of abuse screen determined within 14 days prior to the first dose.
- •Subjects with negative HIV and Hepatitis B and C results.
- •Subjects with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 14 days prior to the first dose.
- •Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements.
- •Subjects and sexual partners used effective contraception methods during the trial and for 3 months after the last dose, for example:
- •Oral contraceptive and condom
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 (including high dose vitamins, dietary supplements or herbal remedies).
- •Receipt of any vaccination within 14 days prior to the first dose.
- •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).
Arms & Interventions
Part A1
Three formulations of Chronocort 30mg were administered to healthy volunteers, with a 7-day washout period between each dose. Each treatment was administered in a randomised, crossover manner.
Intervention: Chronocort
Part A2
Three additional formulations of Chronocort 30mg were administered to healthy volunteers, with a 7-day washout period between each dose. Each treatment was administered in a randomised, crossover manner.
Intervention: Chronocort
Part B
The best formulation of Chronocort was then selected from Parts A1 \& A2. This was then administered in four separate treatment periods, in dosages of 5mg, 10mg, 20mg and 30mg. Each treatment was administered in a randomised, crossover manner.
Intervention: Chronocort
Outcomes
Primary Outcomes
To compare the Tmax of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period. Parts A1 & A2 only
Time Frame: 18 hours
Time at maximum concentration in serum
To compare the AUC0-∞ of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.
Time Frame: 18 hours
Area under the plasma concentration-time curve from zero (0) hours to infinity (∞)
To compare the Cmax of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period. Parts A1 & A2 only
Time Frame: 18 hours
Maximum serum concentration
To compare the CL of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.
Time Frame: 18 hours
Drug clearance (CL) is defined as the volume of plasma in the vascular compartment cleared of drug per unit time
To compare the AUC0-t of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.
Time Frame: 18 hours
Area under the plasma concentration-time curve