A Randomized, Double-blind, Placebo-controlled, Four-way Crossover Study to Evaluate and Compare the Pharmacodynamics and Pharmacokinetics of Fluticasone Furoate /Vilanterol in Different Dose Combination (50/25mcg, 100/25mcg and 200/25mcg) After Single and Repeat Dose Administration From a Novel Dry Powder Device in Healthy Chinese Subjects

GlaxoSmithKline1 site in 1 country16 target enrollmentDecember 5, 2012

ConditionsAsthma

InterventionsFluticasone Furoate/Vilanterol Placebo

DrugsFluticasone Furoate/Vilanterol Placebo

Overview

Phase: Phase 1
Intervention: Fluticasone Furoate/Vilanterol
Conditions: Asthma
Sponsor: GlaxoSmithKline
Enrollment: 16
Locations: 1
Primary Endpoint: Systemic steroid PD effects
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

In this study, fluticasone furoate (FF) and vilanterol (VI) in different dose combinations (50/25mcg, 100/25mcg and 200/25mcg) will be administered from a single dry powder device to evaluate the PD, PK, safety and tolerability of the combination in healthy Chinese subjects. The information gathered will be used as a support of the clinical development program of the fixed dose combination of FF/VI inhalation powder in Chinese population.

Detailed Description

This is a single centre, double-blind, placebo-controlled, four-way cross over, randomized, single and repeat dose study. A total of 16 healthy subjects aged 18-45 years will be randomised with the aim of achieving at least 10 evaluable subjects to each treatment period. The primary objective is to evaluate the systemic steroid PD effects (serum cortisol 24 hour weighted mean on Day 7) of FF and systemic ß-adrenergic PD effects (ECG maximum QTcF 0-4h and whole blood potassium 0-4h in Day 1 and Day 7) of VI; the secondary objectives are aimed to evaluate the PK, safety and tolerability of FF/VI inhalation powder after a single and repeat dose administration.

Registry

clinicaltrials.gov

Start Date

December 5, 2012

End Date

June 4, 2013

Last Updated

8 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•AST, ALT, alkaline phosphatase and bilirubin \<= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
•Healthy male or female between 18 and 45 years of age inclusive.
•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. Subjects with blood pressure values outside the normal range \[systolic (90-139 mmHg) and diastolic (50-89 mmHg)\] and subjects with ECG findings suggestive of a previous MI should always be excluded from enrollment.
•A female subject is eligible to participate if she is of:
•Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<147 pmol/L) is confirmatory\].
•Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 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 until completion of the follow-up visit.
•Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.
•This criterion must be followed from the time of the first dose of study medication until completion of the follow-up visit.
•Body weight \>= 50 kg and BMI within the range 19 - 24 kg/m2 (inclusive).
•Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

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 or on admission to the Unit.
•A positive urinary cotinine test at screening or on admission to the Unit.
•A positive test for HIV antibody.
•History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a 285mL glass of full strength beer or 425mL schooner of light beer or 1 (30mL) measure of spirits or 1 glass (100mL) of wine (NHMRC Guidelines \[NHMRC, 2001\]).
•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: 30 days, 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.
•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.
•History of sensitivity to any of the study medications, or components (magnesium stearate and lactose etc.) or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

Arms & Interventions

FF/VI

50/25 mcg, 100/25 mcg or 200/25 mcg

Intervention: Fluticasone Furoate/Vilanterol

Placebo

matching placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Systemic steroid PD effects

Time Frame: Day 7

Serum cortisol

Systemic ß-adrenergic PD effects

Time Frame: Day 1 and Day 7

Maximum QTcF 0-4h and whole blood potassium

Secondary Outcomes

Plasma concentrations and derived PK parameters for FF/VI(Pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h post dose on Day 1 and pre-dose, 5 min, 15 min, 30 min, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h and 24h post dose on Day 7 and 8.)
Vital signs(Screening Visit, Day 1, Day 7 and Follow-up Visit)
12-lead ECG(Screening Visit, Day 1, Day 7 and Follow-up Visit)
Laboratory tests(Screening Visit, Day 8 of treatment period 4 or early withdrawal Visit and/or follow-up Visit)
Adverse events(From the start of dosing with investigational product and until the follow-up visit.)