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
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK961081 800 microgramme dose
Drug: Fluticasone Propionate 500 microgramme dose
Drug: GSK961081 800 microgramme and Fluticasone Propionate 500 microgramme separately
Drug: GSK961081 800 microgramme Fluticasone Propionate 500 microgrammes in a blend
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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)


Enrollment: 24
Study Start Date: July 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK961081 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
Active Comparator: Fluticasone Propionate 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
Experimental: GSK961081 and Fluticasone Propionate Separately 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
Experimental: GSK961081 and Fluticasone Pripionate in a blend 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

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449799

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01449799     History of Changes
Other Study ID Numbers: 113423
Study First Received: October 6, 2011
Last Updated: June 14, 2012
Health Authority: United Kingdom: National Research Ethics Service (NRES)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Fluticasone
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014