A Two-part, Study to Compare the Pharmacokinetics and Dose Proportionality of up to 6 Chronocort Formulations

Adrenal Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03051893
• Other study ID #: DIUR-002
• Status: Completed
• Phase: Phase 1
• First received: January 11, 2017
• Last updated: February 9, 2017
• Start date: February 2011
• Est. completion date: April 2012

Study information

• Verified date: February 2017
• Source: Diurnal Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy male volunteers between 18 and 60 years of age, inclusive (at screening).

• Subjects with a Body Mass Index (BMI) of 21-28. Body Mass Index = Body weight (kg) / (Height (m))2.

• 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

• Intra-uterine device (IUD) and condom

• Diaphragm with spermicide and 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.

• Subject continued to meet all screening inclusion criteria prior to dosing.

• Subjects with no clinically significant abnormal serum biochemistry, haematology and urine examination values including negative urinary drugs of abuse screen (including alcohol) prior to dosing.

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).

• Participation in a New Chemical Entity clinical study within the previous 16 weeks or a marketed drug clinical study within the previous 12 weeks. (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 have consumed more than 2 units of alcohol per day within seven (7) days prior to the first dose or have consumed any alcohol within the 48 hour period prior to the first dose.

• Donation of 450ml or more of blood within the previous 12 weeks.

• Subjects who smoked (or ex-smokers who had smoked within 6 months prior to first dose).

• Subjects who worked shifts (i.e. regularly alternated between days, afternoons and nights).

Related Conditions & MeSH terms

• Adrenal Hyperplasia, Congenital
• Adrenal Insufficiency
• Adrenogenital Syndrome
• Congenital Adrenal Hyperplasia
• Hyperplasia

Intervention

Drug:
• Chronocort
Modified formulation of hydrocortisone

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Diurnal Limited	Simbec Research

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the Tmax of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period. Parts A1 & A2 only	Time at maximum concentration in serum	18 hours
Primary	To compare the Cmax of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period. Parts A1 & A2 only	Maximum serum concentration	18 hours
Primary	To compare the AUC0-t of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.	Area under the plasma concentration-time curve	18 hours
Primary	To compare the AUC0-8 of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.	Area under the plasma concentration-time curve from zero (0) hours to infinity (8)	18 hours
Primary	To compare the CL of six formulations of Chronocort® (30 mg, dosed at night) over an 18 hour period.	Drug clearance (CL) is defined as the volume of plasma in the vascular compartment cleared of drug per unit time	18 hours