GW824575 First Time in Human

NCT01551771 | Terminated Phase 1

• 1 other identifier: 115802
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Retinal Diseases

Keywords

CCR3 antagonist

Outcome Measures

Primary Outcomes (2)

• Subject tolerability as measured by the number (and frequency) of subjects who experience adverse events after single ascending doses of GW824575

  To assess the safety and tolerability of single doses of GW824575 in healthy male subjects.

  Parts A and D - Through the expected 48-hour duration of hospital stay.Through the expected 48-hour duration of hospital stay.

• Subject tolerability as measured by the number (and frequency) of subjects who experience adverse events after repeat doses of GW824575

  To assess the safety and tolerability of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age

  Part B through the expected 23-day duration of hospital stay.

Secondary Outcomes (7)

• Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after single dosing.

  Parts A and D - predose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours of each hospital stay.

• Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after repeat dosing.

  predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24, hours on Day 1 of dosing and on Day 21 of dosing in Part B.

• Single dose - eosinophil shape change assay

  24 to 27 hours post dose.

• Repeat dose - eosinophil shape change assay

  Part B at 3, 8 and 24 hours post last dose on Day 21.

• Urine, serum and bile sampling for GW824575

  Part B (only) at 12-hours after 12 days of repeat dosing.

Study Arms (2)

GW824575

EXPERIMENTAL

Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule

Drug: GW824575 matched-placebo

GW824575 matched-placebo

PLACEBO COMPARATOR

Placebo

Drug: GW824575

Interventions

GW824575 DRUG

Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule

GW824575 matched-placebo

GW824575 matched-placebo DRUG

Placebo

GW824575

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• For subjects in Parts A or D - Male subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• For subjects in Part B - Male subjects greater than or equal to 50 years of age, at the time of signing the informed consent..
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 4 months post-last dose.
• Body weight greater than or equal to 55 kg and BMI within the range 18 - 31 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTc \< 450 msec.
• Normotensive, after having rested quietly in a supine position for at least 15 minutes, with a systolic blood pressure less than or equal to 120 mmHg and diastolic blood pressure less than or equal to 80mmHg and a heart rate less than or equal to 100 beats per minute. Subjects with "pre-hypertension" (systolic blood pressure 121-140 mmHg and diastolic blood pressure 81 to 99mmHg) must be cleared by the medical monitor.
• Willingness and ability to swallow multiple size 00 capsules as part of study participation.
• For subjects in Part B only - Best-corrected visual acuity better than 20/80 (Snellen equivalent; 54 or more ETDRS letters) in both eyes.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• Significant infection within 4 weeks prior to the first dosing day.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months (12 weeks), 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Unable to refrain from prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and throughout the study, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Any prior intraocular surgery, excluding cataract surgery.
• Any prior eye surgery within three months to first dose of study medication.
• Subjects with glaucoma (controlled or uncontrolled).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

• Results for study 115802 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Retinal Diseases

Condition Hierarchy (Ancestors)

Eye Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: March 13, 2012
• Study Start: February 1, 2012
• Primary Completion: April 12, 2012
• Study Completion: April 12, 2012
• Last Updated: October 19, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)