An Open Label Study in Healthy Volunteers to Compare Chronocort® to Hydrocortisone

NCT03019614 | Completed Phase 1

• 1 other identifier: DIUR-001
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was an open label, randomized, single dose, three period crossover pharmacokinetic study of Chronocort® in 30 healthy male volunteers. The study was conducted in smaller sub groups (Group 1, n=18 and Group 2, n=12).

Conditions

Congenital Adrenal Hyperplasia; Adrenal Insufficiency

Outcome Measures

Primary Outcomes (7)

• Derived pharmacokinetic parameter: Tmax

  Tmax measures the time at which Cmax - maximum serum concentration - is observed

  24 hours

• Derived pharmacokinetic parameter: Tlag

  Tlag measures the delay between dosing and being able to observe the drug/metabolite within the sampling area (e.g., blood serum)

  24 hours

• Derived pharmacokinetic parameter: Cmax

  Cmax measures the time taken for the drug/metabolite to reach maximum serum concentration

  24 hours

• Derived pharmacokinetic parameter: AUC(0 - t) (Area under the curve)

  Area under the serum concentration versus time curve from time

  24 hours

• Derived pharmacokinetic parameter: AUC(0-∞)(Area under the curve)

  Area under the serum concentration versus time curve from time = 0h extrapolated to infinity

  24 hours

• Derived pharmacokinetic parameter: CL

  Time to drug clearance

  24 hours

• Derived pharmacokinetic parameter: T1/2

  Time required to reach 1/2 Cmax

  24 hours

Study Arms (2)

Group 1

EXPERIMENTAL

Volunteers in group 1 received the following interventions: Chronocort® 30 mg given at night (\~ 23:00h) as a combination of one 10mg capsule and one 20mg capsule (n=18). Chronocort® 30mg given as one 20mg capsule at night (\~ 23:00h) and as one 10mg capsule in the morning (\~ 7:00h) following the initial night-time dose (n=18). Hydrocortisone 30mg given at night (\~ 23:00h) given as three 10mg tablets (n=18). Each administration of IMP was separated by a washout period of at least 7 days.

Drug: Hydrocortisone; Drug: Chronocort

Group 2

EXPERIMENTAL

Volunteers in group 2 received the following interventions: Chronocort® 5mg given at night (\~ 23:00h) as one 5mg capsule (n=12). Chronocort® 10mg given at night (\~ 23:00h) as one 10mg capsule (n=12). Chronocort® 20mg given at night (\~ 23:00h) as one 20mg capsule (n=12). Each administration of IMP was separated by a washout period of at least 7 days.

Drug: Chronocort

Interventions

Hydrocortisone DRUG

Generic hydrocortisone

Group 1

Chronocort DRUG

Modified formulation of hydrocortisone

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 of the start of the study. The parameters measured included those shown in Appendix 3 of the Study Protocol.
• Subjects with a negative urinary drugs of abuse screen (including alcohol), determined within 14 days of the start of the study.
• 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 of the start of the study.
• Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements.
• Subjects and sexual partners must have used effective contraception methods during the trial and for 3 months after the last dose, for example:
• Oral contraceptive + condom
• Intra-uterine device (IUD) + condom
• Diaphragm with spermacide + condom
• Subjects must have been available to complete the study.
• Subjects must have satisfied a medical examiner about their fitness to participate in the study.
• Subjects must have provided written informed consent to participate in the study.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
• Receipt of regular medication within 14 days of the first study day (including high dose vitamins, dietary supplements or herbal remedies).
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• A clinically significant history of previous allergy / sensitivity to Hydrocortisone.
• 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.
• Subjects who had consumed more than 2 units of alcohol per day within seven (7) days prior to the first dose or had consumed any alcohol within the 48 hour period prior to the first dose.
• Donation of 450ml or more blood within the previous 12 weeks.
• Subjects who worked shifts (i.e. regularly alternated between days, afternoons and nights).

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• Simbec Research: collaborator

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital; Adrenal Insufficiency

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Salvatore Febbraro

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: March 1, 2010
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: January 12, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share