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

Diurnal

Status and phase: Completed; Phase 1

Conditions: Adrenal Insufficiency; Congenital Adrenal Hyperplasia

Treatments: Drug: Chronocort

Study type: Interventional

Funder types: Industry

Identifiers

NCT03051893

DIUR-002

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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28 participants in 3 patient groups

Part A1

Experimental group

Description:

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.

Treatment:

Drug: Chronocort

Part A2

Experimental group

Description:

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.

Treatment:

Drug: Chronocort

Part B

Experimental group

Description:

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.

Treatment:

Drug: Chronocort