NCT01551771

GW824575 First Time in Human

A Single-centre, Masked, Placebo-controlled Four Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of the CC-chemokine Receptor 3 (CCR3) Antagonist, GW824575, Coadministered With or Without Food in Healthy Male Subjects

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: Male
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study is the first administration of GW824575 in humans. This will be a single centre, masked, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GW824575, given as single and repeated oral doses to healthy male subjects. The study will be comprised of 4 parts and enroll approximately 40 subjects: Part A will consist of two cohorts of 8 healthy male subjects to assess the safety, tolerability, PK, and PD of ascending single oral doses of GW824575. All available safety, tolerability, and PK data will be monitored prior to each dose escalation. In order to support the possible indication for age-related macular degeneration (AMD), Part B will be one cohort of 12 subjects to examine the safety, tolerability, PK, and PD of a repeated dose of GW824575 over 21 days in healthy male subjects who are greater than or equal to 50 years of age. The total daily dose in this cohort will not exceed the maximum tolerated dose (MTD) from Parts A and D. Subjects in this cohort will undergo ophthalmology assessments before receiving investigational product and after Day 7 of the 21-day in-patient treatment, after steady state has been reached. As part of protocol amendment 2, Part C (Cohort 4) is removed from the protocol. Part D, added under protocol amendment 2, will consist of one cohort of 12 healthy male subjects to assess safety, tolerability, PK, and PD of ascending single doses of GW824575 as well as the effect of food on the PK of GW824575.

Detailed description

Part A will consist of two cohorts of healthy male subjects to assess the safety, tolerability, and PK of ascending single oral doses of GW824575. The sponsor will review available safety, tolerability, and PK data and, where available, PD receptor occupancy (from the eosinophil shape change data) data before each dose escalation. Outcome measures in Part A will be assessed and presented through 48 hours post-dose for each of up to 4 single dose escalations per cohort. Part B will be one cohort to examine the safety, tolerability and PK of a repeated dose of GW824575 over 21 days in healthy male subjects who are greater than or equal to 50 years of age. Subjects in this cohort will undergo ophthalmic assessments before receiving investigational product and after Day 7 of the 21-day in-patient treatment, after steady state has been reached. The PD endpoints such as receptor occupancy will be assessed. The dosing regimen (once or twice daily) will be determined by PK data from Part A; however, regardless of dosing regimen, subjects will only receive a single dose in the morning on Days 1 and 21 of the treatment period. Outcome measures in Part B (Cohort 3) will be assessed and presented through 21 days repeat dosing until 48 hours post-dose last dose (i.e., on Day 23). If a safety signal is noted during, or after, the conduct of Cohort 3 of the study; the cohort may be halted or dose down-titrated, and an additional cohort, at a lower dose, may be instituted in Part B as Cohort 5. Dose selection for the additional cohort (Cohort 5) will be informed by the aggregate safety, PK, and PD data available at that time. Part D will consist of one cohort of healthy male subjects. The cohort will 1) explore the effect of a high fat meal on the PK of GW824575 during two treatment periods with approximately 48 hour washout between periods and 2) assess the safety, tolerability, and PK of ascending single oral doses of GW824575 administered in the fasting state or with a standard meal in up to 3 additional treatment periods with at least 6-day washout between periods. The sponsor will review available safety, tolerability, and PK data and, where available, PD RO (from the eosinophil shape change data) data before each dose escalation.

Conditions

• Retinal Diseases

Interventions

Type	Name	Description
DRUG	GW824575	Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule
DRUG	GW824575 matched-placebo	Placebo

Timeline

• Start date: 2012-02-01
• Primary completion: 2012-04-12
• Completion: 2012-04-12
• First posted: 2012-03-13
• Last updated: 2017-10-19

Locations

1 site across 1 country: United Kingdom