Relovair PD PK in Chinese Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone Furoate/Vilanterol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100032
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 8.1. 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.
• No significant abnormality on 12-lead ECG at screening, including the following specific requirements:

Ventricular rate >= 45 beats per minute; PR interval <=210msec; No pathological Q waves; QRS interval to be >= 60msec and <=120msec; The waveforms must enable the QT interval to be clearly defined; QTc interval must be < 450msec (QTcF; machine or manual reading) based on a single ECG value, or an average from three ECGs obtained over a brief recording period.

• Subjects who are current non-smokers, who have not used any tobacco products in the 12 month period preceding the screening visit, and have a pack history of <=5 pack years.
• Subjects who are able to use the inhalation device satisfactorily.

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.
• History of milk protein allergy.
• History of any adverse reaction including immediate or delayed hypersensitivity to any ICS, β2-agonist or sympathomimetic drug.
• Blood donation or sampled as a study subject within three months preceding the first dose of study drug and blood donation during the entire study.
• Pregnant females as determined by positive urine pregnancy test at screening or prior to dosing.
• Lactating females.
• Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
• The subject has taken oral corticosteroids less than 8 weeks before the screening visit.
• The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; matching placebo	Drug: Placebo; Placebo inhaled once daily for 7 days in each treatment period.
Experimental: FF/VI; 50/25 mcg, 100/25 mcg or 200/25 mcg	Drug: Fluticasone Furoate/Vilanterol; 50/25 or 100/25 or 200/25 mcg inhaled once daily for 7 days in each treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic steroid PD effects	Serum cortisol	Day 7
Systemic ß-adrenergic PD effects	Maximum QTcF 0-4h and whole blood potassium	Day 1 and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations and derived PK parameters for FF/VI	Single dose: Cmax, tmax, t1/2, AUC(0-t) (AUC from zero to the last quantifiable timepoint) and AUC(0-t') (AUC from zero to the last common quantifiable timepoint in the dose group). Repeat dose: FF: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t'), Ro and RCmax, Css_min and AUCss , Css_av, DF; VI: Cmax, tmax, t1/2, AUC(0-t) and AUC(0-t')	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	blood pressure and heart rate	Screening Visit, Day 1, Day 7 and Follow-up Visit
12-lead ECG	12-lead ECG	Screening Visit, Day 1, Day 7 and Follow-up Visit
Laboratory tests	Clinical chemistry, hematology and urinalysis	Screening Visit, Day 8 of treatment period 4 or early withdrawal Visit and/or follow-up Visit
Adverse events	adverse events	From the start of dosing with investigational product and until the follow-up visit.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2012
• Primary Completion (Actual): June 4, 2013
• Study Completion (Actual): June 4, 2013

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: October 18, 2012
• First Posted (Estimate): October 22, 2012

Study Record Updates

• Last Update Posted (Actual): July 25, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Safety and tolerability; Healthy Chinese subjects; Fluticasone furoate (FF); novel dry powder device; vilanterol(VI)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 115199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Study Data/Documents

1. Study Protocol
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 115199
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register