Dose Proportionality Study: Blood Levels of Fluticasone Furoate (FF) and Vilanterol (VI) Following Different Doses of FF/VI Via an Inhaler

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01213849
First received: October 1, 2010
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to demonstrate dose proportionality of fluticasone furoate (FF) and equivalence of vilanterol (VI)following single dose administration of FF/VI via the novel dry powder inhaler in healthy subjects.


Condition Intervention Phase
Asthma
Drug: Fluticasone furoate 50 mcg (4 inhalations)
Drug: Fluticasone furoate 100 mcg (4 inhalations)
Drug: Fluticasone furoate 200 mcg (4 inhalations)
Drug: Vilanterol 25 mcg (4 inhalations)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, Randomised, 3-way Crossover Single Dose Study to Demonstrate Dose Proportionality of Fluticasone Furoate (FF) and Equivalence of Vilanterol (VI) When Administered as FF/VI Inhalation Powder From the Novel Dry Powder Inhaler in Healthy Subjects.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Fluticasone furoate area under concentration-time curve (AUC) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
  • Fluticasone furoate maximum observed concentration (Cmax) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
  • Vilanterol area under concentration-time curve (AUC) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
  • Vilanterol maximum observed concentration (Cmax) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fluticasone furoate time of occurence of maximum concentration (tmax) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
  • Vilanterol time of occurence of maximum concentration (tmax) [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 200/100 mcg fluticasone furoate/vilanterol
4 inhalations of 50/25 mcg fluticasone furoate/vilanterol
Drug: Fluticasone furoate 50 mcg (4 inhalations)
4 inhalations of 50 mcg strength
Drug: Vilanterol 25 mcg (4 inhalations)
4 inhalations of 25 mcg strength
Experimental: 400/100 mcg fluticasone furoate/vilanterol
4 inhalations of 100/25 mcg fluticasone furoate/vilanterol
Drug: Fluticasone furoate 100 mcg (4 inhalations)
4 inhalations of 100 mcg strength
Drug: Vilanterol 25 mcg (4 inhalations)
4 inhalations of 25 mcg strength
Experimental: 800/100 mcg fluticasone furoate/vilanterol
4 inhalations of 200/25 mcg fluticasone furoate/vilanterol
Drug: Fluticasone furoate 200 mcg (4 inhalations)
4 inhalations of 200 mcg strength

Detailed Description:

The study will be an open-label, randomised, 3-way cross-over single dose study in 24 healthy subjects to demonstrate dose proportionality of fluticasone furoate (FF) and equivalence of vilanterol (VI) following single dose administration of FF/VI via the novel dry powder inhaler. In each of 3 treatment periods, subjects will receive 4 inhalations of 50/25 mcg, 100/25 mcg, 200/25 mcg FF/VI. Blood samples will be taken for pharmacokinetic analysis and safety (12-lead ECGs, clinical laboratory test, vital signs, adverse events) will be monitored following each dose.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <or= 1.5xULN
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Male or female between 18 and 65 years of age inclusive.
  • A female subject is eligible to participate if she is of:

Non-child-bearing potential defined as post-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea.

Child-bearing potential and agrees to use one of the approved contraception methods until 16 weeks after the last dose.

  • Male subjects with female partners of child-bearing potential must agree to use one of the approved contraception methods until 16 weeks after the last dose.
  • Body Mass Index (BMI) within range 18.5-29.0 kg/m2 (inclusive).
  • Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Average QTcF < 450 msec.
  • No clinically significant abnormality on the Holter electrocardiogram (ECG) at screening.
  • 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 < or = 5 pack years.
  • Able to satisfactorily use the dry powder inhaler.

Exclusion Criteria:

  • As a result of medical interview, physical examination or screening investigations, the principal investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
  • The subject has a history of breathing problems in adult life (e.g. history of asthmatic symptomatology). Screening lung function tests (forced expiratory volume in 1 minute (FEV1)) will be performed to confirm normal lung function parameters (>or=85% predicted).
  • Subjects who have suffered a lower respiratory tract infection within 4 weeks of the screening visit.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
  • A positive HIV antibody.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • History of heavy regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units for males or >14 units for females.
  • History or regular use of tobacco- or nicotine-containing products within 12 months prior to screening.
  • Positive carbon monoxide or alcohol breath test at screening or on admission to the unit.
  • A positive pre-study urine drug screen or when randomly tested during the study.
  • 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, 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.
  • The subject has taken systemic, oral or depot corticosteroids less than 12 weeks before the screening visit.
  • The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
  • History of sensitivity or adverse reaction to any of the study medications including immediate or delayed hypersensitivity to any beta-agonist, sympathomimetic drug, or an intranasal, inhaled or systemic corticosteroid; known suspected sensitivity to the constituents of the new powder inhaler (lactose or magnesium stearate) or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates participation.
  • History of severe milk protein allergy.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months of the start of the study.
  • Pregnant females as determined by positive serum hCG test at screening or by positive serum/urine hCG test prior to dosing.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  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: NCT01213849

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: NCT01213849     History of Changes
Other Study ID Numbers: 102932
Study First Received: October 1, 2010
Last Updated: September 6, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
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 21, 2014