Clinical trial NCT00549497: A Randomized Study Evaluating Steroid Hormone Levels, Safety And Tolerability Of GW870086X In Healthy Volunteers
Official title: A Randomized, Double-blind, Placebo-controlled, Dose Ascending, 3-cohort Parallel Group Study to Measure the Systemic Cortisol Profile and Evaluate the Safety, Tolerability and Pharmacokinetics of GW870086X, Administered as Single Doses (12mg and 15mg), and Repeat Doses Over 3 Days (6mg, 12mg and 15mg) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: GW870086X, inhaled, asthma, cortisol, pharmacokinetics, osteocalcin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-25
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: GW870086X is a novel inhaled steroid that has an improved safety profile over other steroids but is also less potent. This study will look at higher doses to confirm the improved safety profile.

Detailed description: A randomized, double-blind, placebo-controlled, dose ascending, 3-cohort parallel group study to measure the systemic cortisol profile and evaluate the safety, tolerability and pharmacokinetics of GW870086X, administered as single doses (12mg and 15mg),and repeat doses over 3 days (6mg, 12mg and 15mg) in healthy male subjects.

Eligibility criteria: Inclusion criteria:

* Healthy male subjects
* Liver function tests normal
* 18 - 45 years old
* Non smoker
* Can provide written informed consent
* Available to complete the whole trial
* Can use the inhalation device correctly
* Able to read, understand and write English

Exclusion criteria:

* Deemed suitable healthy subject
* History to sensitivity to the study medication
* Any history of breathing problems in adult life
* Participated in another trial within 30 days or 5 half-lives of the new chemical entity
* Exposed to more than 4 new chemical entities within 12 months
* Donated \>500 mL blood within 2 months of screening
* Haemoglobin level \< 13g/dl
* Use of prescription or non-prescription drugs within 7 days of first dose
* Taking drugs that significantly inhibit cytochrome P450 subfamily enzyme CYP3A4
* Drinks more than 4 units a day or 28 units a week
* Cannot use DISKHALER device correctly
* Positive HepB, HepC within 3 months of screening
* Positive HIV test
* Positive pre study drug/alcohol screen
* Significant cardiac conduction abnormalities
* Risk of non-compliance

Primary outcomes:
measure: Effect of GW870086X on cortisol levels (naturally produced steroid hormone) in the body during a single dose and after 3 days of dosing
timeFrame: 3 days
Secondary outcomes:
measure: Safety & tolerability measures: heart rate, blood pressure, ECG, safety laboratory tests, lung function
timeFrame: 3 days
measure: Total urinary free cortisol excretion
timeFrame: over 24 hours on Day 1 and Day 3.
measure: Serum osteocalcin weighted mean
timeFrame: over 24 hours on Day 3.
measure: Fasting glucose
timeFrame: on Day 1
measure: mRNA steroid responsive gene panel
timeFrame: 3 days
measure: Plasma concentrations of GW870086X and GW870086X pharmacokinetic parameters (including AUC, Cmax, t1/2 and tmax).
timeFrame: 3 days
measure: Plasma concentrations of GW870086X and derived pharmacokinetic parameters
timeFrame: 3 days
measure: Cortsiol urine concentrations
timeFrame: 3 days
measure: Osteocalcin serum concentrations
timeFrame: 3 days
Other outcomes:
Locations:
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Dolle S, Hielscher N, Bareille PJ, Hardes K, Robertson J, Worm M. Clinical efficacy and tolerability of a novel selective corticosteroid in atopic dermatitis--two randomised controlled trials. Skin Pharmacol Physiol. 2015;28(3):159-66. doi: 10.1159/000367696. Epub 2015 Jan 20.