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An Investigation of the Pharmacokinetics of GSK961081 and Fluticasone Propionate in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01449799
First received: October 6, 2011
Last updated: June 14, 2012
Last verified: June 2012

October 6, 2011
June 14, 2012
July 2011
September 2011   (final data collection date for primary outcome measure)
Plamsa concentrations and derived pharmacokinetic parameters of GSK961081 and fluticasone propionate [ Time Frame: From dosing to 24 hours post-dose ] [ Designated as safety issue: No ]
Maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve, and apparent terminal phase half-life (t1/2)] for GSK961081 and fluticasone propionate
Same as current
Complete list of historical versions of study NCT01449799 on ClinicalTrials.gov Archive Site
  • Serum Cortisol [ Time Frame: From dosing to 24 hours post-dose ] [ Designated as safety issue: No ]
    Concentration of the hormone cortisol in serum
  • Urinary Cortisol [ Time Frame: From dosing to 24 hours post-dose ] [ Designated as safety issue: No ]
    Concentration of the hormone cortisol in urine
  • Heart Rate Changes [ Time Frame: From dosing to 4 hours post-dose ] [ Designated as safety issue: No ]
    The maximum change and weighted mean change in heart rate from baseline (pre-dose)
Same as current
Not Provided
Not Provided
 
An Investigation of the Pharmacokinetics of GSK961081 and Fluticasone Propionate in Healthy Volunteers
A Randomised, Double-blind, Double-dummy, Single Dose, Four Way Cross-over Study to Compare the Pharmacokinetics and Pharmacodynamics of GSK961081 and Fluticasone Propionate When Administered Alone, Concurrently and as a Combination Blend in Healthy Subjects

In the current study GSK961081 and fluticasone propionate will be administered in a blended formulation from a single device and compared with GSK961081 and fluticasone propionate administered alone and concurrently. This is a single centre, randomized, double-blind, double dummy, single dose, four way cross-over study investigating the pharmacokinetics and pharmacodynamics of GSK961081 and fluticasone propionate when administered alone, concurrently and as a combination blend in healthy subjects.

This will be the first time that GSK961081 and fluticasone propionate will be administered as a blend in humans. In previous clinical studies conducted in Chronic Obstructive Pulmonary Disease (COPD) patients, GSK961081 has been administered on a background of fluticasone propionate without any observed systemic pharmacodynamic interaction. In this study GSK961081 and fluticasone propionate will be administered in a blended formulation from a single device and compared with GSK961081 and fluticasone propionate administered alone and concurrently. The aim of the study will be to investigate any differences in pharmacodynamics and/or pharmacokinetics for GSK961081 and fluticasone propionate when administered as the blend, concurrently or alone.

Pharmacokinetic, pharmacodynamic and safety information will be gathered to assess the suitability of the GSK9610981/fluticasone propionate blend for further development.Each subject will receive four treatments (GSK961081 alone, fluticasone propionate alone, GSK961081 and fluticasone propionate concurrently, and GSK961081/fluticasone propionate blend) in randomized order, in four treatment periods, each separated by a washout period of at least a week. All treatments will be administered via a DISKUS inhaler.

Pharmacokinetics, pharmacodynamics and safety will be assessed by measurement of plasma GSK961081, plasma fluticasone propionate, serum cortisol, urine cortisol, blood glucose, serum potassium, Forced Expiratory Volume in one second (FEV1), heart rate, 12-lead Electrocardiograms (ECGs), clinical laboratory tests and collection of adverse events (AEs).

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Drug: GSK961081 800 microgramme dose
    To be provided via a combination of 4 inhalers - one 400 microgramme GSK961081 Diskus inhalation, a second 400 microgramme GSK961081 Diskus inhalation and one inhalation each from two separate placebo Diskus inhalers
  • Drug: Fluticasone Propionate 500 microgramme dose
    To be provided via a combination of 4 inhalers - one 250 microgramme fluticasone propionate Diskus inhalation, a second 250 microgramme fluticasone proopionate Diskus inhalation, and one inhalation each from two separate placebo Diskus inhalers
  • Drug: GSK961081 800 microgramme and Fluticasone Propionate 500 microgramme separately
    To be provided via a combination of 4 inhalers - one 400 microgramme GSK961081 Diskus inhalation, a second 400 microgramme GSK961081 Diskus inhalation, one 250 microgramme fluticasone propionate Diskus inhalation, and a second fluticasone propionate 250 microgramme Diskus inhalation
  • Drug: GSK961081 800 microgramme Fluticasone Propionate 500 microgrammes in a blend
    To be provided via a combination of 4 inhalers - one inhalation of a Diskus inhaler containing a blend of 400 microgramme of GSK961081 and 250 microgramme of fluticasone propionate per inhalation, a second inhalation of a Diskus inhaler containing a blend of 400 microgramme of GSK961081 and 250 microgramme of fluticasone propionate per inhalation, and one inhalation each from two separate placebo inhalers
  • Experimental: GSK961081
    Intervention: Drug: GSK961081 800 microgramme dose
  • Active Comparator: Fluticasone Propionate
    Intervention: Drug: Fluticasone Propionate 500 microgramme dose
  • Experimental: GSK961081 and Fluticasone Propionate Separately
    Intervention: Drug: GSK961081 800 microgramme and Fluticasone Propionate 500 microgramme separately
  • Experimental: GSK961081 and Fluticasone Pripionate in a blend
    Intervention: Drug: GSK961081 800 microgramme Fluticasone Propionate 500 microgrammes in a blend
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
September 2011
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  2. Healthy as determined by the Investigator based on a medical evaluation including medical history, physical examination, laboratory tests and lung function testing. 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 agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and outcome.
  3. A female subject of child bearing potential, is eligible if she agrees to use one of the contraception methods listed in Section 8.1 of the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for 5 half-lives after the end of the study (i.e. until after the follow-up visit is complete).
  4. Body Mass Index (BMI) within the range 19.0 - 29.9 kilogram per square meter (kg/m2) (inclusive).
  5. Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin less than 1.5 times the upper limit of normal (<1.5xULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%).
  6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  7. Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio greater than or equal to 0.7.
  8. Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of less than or equal to 10 pack years.

[number of pack years = (number of cigarettes per day/20) x number of years smoked]

Exclusion Criteria:

  1. Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or electrocardiogram (ECG, 12-lead)
  2. History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (around 240 millilitres, ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
  3. QTc value corrected for Bassett or Fredericia [QTc(B) and QTc(F)] at screening greater than 450 milliseconds on an individual ECG, the 3 screening ECGs are not within 10% of the mean QTC value, a PR interval outside the range 120-210 msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
  4. A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
  5. A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
  6. 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: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  7. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  8. Use of 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  9. 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.
  10. Where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 90 day period.
  11. Pregnant females as determined by positive serum Human Chorionic Gonadotrophin (hCG test) at screening or prior to dosing.
  12. Lactating females.
  13. Unwillingness or inability to follow the procedures outlined in the protocol.
  14. Subject is mentally or legally incapacitated.
  15. A history of respiratory disease (i.e. history of asthmatic symptoms) in the last 10 years.
  16. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  17. A positive test for human immunodeficiency virus (HIV) antibody.
  18. Urinary Cotinine/ Breath carbon monoxide (CO) levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  19. Night shift workers
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01449799
113423
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
June 2012

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