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GW824575 First Time in Human

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01551771
Recruitment Status : Terminated
First Posted : March 13, 2012
Last Update Posted : October 19, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE February 9, 2012
First Posted Date  ICMJE March 13, 2012
Last Update Posted Date October 19, 2017
Actual Study Start Date  ICMJE February 1, 2012
Actual Primary Completion Date April 12, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2012)
  • Subject tolerability as measured by the number (and frequency) of subjects who experience adverse events after single ascending doses of GW824575 [ Time Frame: Parts A and D - Through the expected 48-hour duration of hospital stay.Through the expected 48-hour duration of hospital stay. ]
    To assess the safety and tolerability of single doses of GW824575 in healthy male subjects.
  • Subject tolerability as measured by the number (and frequency) of subjects who experience adverse events after repeat doses of GW824575 [ Time Frame: Part B through the expected 23-day duration of hospital stay. ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2012)
  • Subject tolerability of single ascending doses of GW824575 [ Time Frame: Through the expected 48-hour duration of hospital stay. ]
    To assess the safety and tolerability of single doses of GW824575 in healthy male subjects.
  • Subject tolerability of repeat doses of GW824575 [ Time Frame: Part B through the expected 23-day duration of hospital stay. Part C through the expected 16-day duration of hospital stay. ]
    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 and/or asthmatic male subjects.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2012)
  • Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after single dosing. [ Time Frame: 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. ]
    To characterise the PK profile of single doses of GW824575 in healthy male subjects
  • Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after repeat dosing. [ Time Frame: 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. ]
    To characterise the PK profile of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age
  • Single dose - eosinophil shape change assay [ Time Frame: 24 to 27 hours post dose. ]
    To determine the PD effect of single doses of GW824575 in healthy male subjects.
  • Repeat dose - eosinophil shape change assay [ Time Frame: Part B at 3, 8 and 24 hours post last dose on Day 21. ]
    To determine the PD effect of repeat doses of GW824575 in healthy male subjects who are greater than 50 years of age
  • Urine, serum and bile sampling for GW824575 [ Time Frame: Part B (only) at 12-hours after 12 days of repeat dosing. ]
    To investigate the metabolism of GW824575 following single and repeat doses in healthy male subjects who are greater than or equal to 50 years of age.
  • Changes in safety laboratory values after single ascending doses of GW824575 [ Time Frame: Parts A and D - At the conclusion of the expected 48-hour duration of hospital stay. ]
    To assess the safety of single dose of GW824575 in healthy male subjects
  • Changes in safety laboratory values after repeat dosing with GW824575 [ Time Frame: Part B through the expected 22-day duration of hospital stay. ]
    To assess the safety of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2012)
  • Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after single dosing. [ Time Frame: predose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours of each hospital stay. ]
    To characterise the PK profile of single doses of GW824575 in healthy male subjects
  • Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GW824575 after repeat dosing. [ Time Frame: predose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours on Day 1 of dosing and on Day 21 of dosing in Part B and Day 14 of dosing in Part C. ]
    To characterise the PK profile of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age and/or asthmatic male subjects.
  • Single dose - eosinophil shape change assay [ Time Frame: 24 to 27 hours post dose. ]
    To determine the PD effect of single doses of GW824575 in healthy male subjects.
  • Repeat dose - eosinophil shape change assay [ Time Frame: Part B at 24 to 27 hours post last dose on Day 21. Part C at 24 to 27 hours post last dose on Day 14. ]
    To determine the PD effect of repeat doses of GW824575 in healthy male subjects who are greater than 50 years of age and/or asthmatic subjects.
  • Urine, serum and bile sampling for GW824575 [ Time Frame: Part B (only) at 12-hours after 12 days of repeat dosing. ]
    To investigate the metabolism of GW824575 following single and repeat doses in healthy male subjects who are greater than or equal to 50 years of age.
  • Number (and frequency) of subjects who experience adverse events after single doses of GW824575 [ Time Frame: Through the expected 48-hour duration of hospital stay ]
    To assess the safety of single dose of GW824575 in healthy male subjects
  • Number (and frequency) of subjects who experience adverse events after repeat dosing with GW824575 [ Time Frame: Part B through the expected 23-day duration of hospital stay. Part C through the expected 16-day duration of hospital stay. ]
    To assess the safety of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age and/or asthmatic male subjects
  • Changes in safety laboratory values after single ascending doses of GW824575 [ Time Frame: At the conclusion of the expected 48-hour duration of hospital stay. ]
    To assess the safety of single dose of GW824575 in healthy male subjects
  • Changes in safety laboratory values after repeat dosing with GW824575 [ Time Frame: Part B through the expected 23-day duration of hospital stay. Part C through the expected 16-day duration of hospital stay. ]
    To assess the safety of repeat doses of GW824575 in healthy male subjects who are greater than or equal to 50 years of age and/or asthmatic male subjects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GW824575 First Time in Human
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Diagnostic
Condition  ICMJE Retinal Diseases
Intervention  ICMJE
  • Drug: GW824575
    Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule
  • Drug: GW824575 matched-placebo
    Placebo
Study Arms  ICMJE
  • Experimental: GW824575
    Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule
    Intervention: Drug: GW824575 matched-placebo
  • Placebo Comparator: GW824575 matched-placebo
    Placebo
    Intervention: Drug: GW824575
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 30, 2012)
16
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2012)
40
Actual Study Completion Date  ICMJE April 12, 2012
Actual Primary Completion Date April 12, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).
  • Inability to withhold contact lens wear from the time of the screening ophthalmic assessments until the treatment ophthalmic assessments have been performed (the wearing of glasses is permitted).
  • Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol).
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01551771
Other Study ID Numbers  ICMJE 115802
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP