Clinical trial NCT01837316: A Study to Assess the Bronchodilator Effect of a Single Dose of Fluticasone Furoate (FF)/ Vilanterol (VI) 100/25 Micrograms (mcg) Combination When Administered in Adult Patients With Asthma
Official title: A Randomized, Double-blind, Placebo-controlled Cross-over Study to Determine the Bronchodilator Effect of a Single Dose of Fluticasone Furoate (FF)/ Vilanterol (VI) 100/25 mcg Combination Administered in the Morning in Adult Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: pharmacodynamics
FF/VI
asthma
duration of action
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-04-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study will be a randomized, double-blind, placebo controlled cross-over study in 32 adult subjects with moderately severe asthma. In this study the bronchodilator effect of a single morning dosing of FF/VI combination 100/25 mcg will be determined by spirometry. After the screening the subject will be randomized and will be assigned to one of two treatment sequences (AB or BA, where A is placebo and B is FF/VI 100/25 mcg). Between the two treatment periods there will be a washout period of 7-14 days. A serial forced expiratory volume in one second (FEV1) measurements will be taken at 15, 30 minutes, 1, 2, 4, 12, 24, 36, 48, 60 and 72 hours post dose. Safety assessments will include vital signs, electrocardiograms (ECGs), adverse event (AE) monitoring and laboratory safety tests however, these will not constitute study endpoints. The results of the study will provide supporting information to prescribers on the bronchodilator effect of FF/VI over 72 hours.


Eligibility criteria: Inclusion Criteria:

* Asthma: A doctor diagnosis of asthma.
* Age of subject: 18 to 65 years of age inclusive, at the time of signing the informed consent.
* Severity of Disease: A screening pre-bronchodilator FEV1 \>=60% of predicted.
* Reversibility of Disease: Demonstrated presence of reversible airway disease at screening.
* Current Therapy: On inhaled corticosteroid (ICS) with or without a SABA for at least 12 weeks prior to screening. Able to stop current Short-Acting Beta2-Agonists (SABA) and replace with albuterol/salbutamol inhaler
* Body weight and BMI: Body weight \>=50 kilogram (kg) and Body Mass Index (BMI) within the range 19.0 to 29.9 kilogram per square meter (kg/m\^2) (inclusive).
* Gender: Male or female. A female subject is eligible to participate if she is of:

Non-childbearing potential. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.

Child-bearing potential and agrees to use one of the contraception methods 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.

* Liver criteria: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2x Upper limit of normal (ULN); alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Consent: Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

* A history of life-threatening asthma.
* Other significant pulmonary diseases: pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
* Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of screening that; led to a change in asthma management OR in the opinion of the Investigator, is expected to affect the subject's asthma status OR the subject's ability to participate in the study.
* Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of screening or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to screening.
* Concomitant Medications: Use of the medications, ICS were prohibited for each study period from 24 hours prior to dosing to 72 hours after dosing; Long acting beta agonist (LABA), leukotriene receptor antagonist (LTRA) or long acting muscarinic anatagonist (LAMA) were prohibited for 12 weeks prior to screening; High doses of an ICS were prohibited for 8 weeks prior to screening; Oral steroids were prohibited for 12 weeks prior to screening; Potent CYPP3A4 inhibitors were prohibited within 4 weeks prior to dosing. The following medications may not be used during the study from first dosing to the end of period 2 inclusive: Anticonvulsants, Polycyclic antidepressants, β-adrenergic blocking agents, Phenothiazines and Monoamine oxidase (MAO) inhibitors.
* Other concurrent Diseases/Abnormalities: A subject has any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the study results if the condition/disease exacerbated during the study.
* Oropharyngeal examination: A subject will not be eligible if he/she has clinical visual evidence of oral candidiasis at screening.
* Pregnancy and Lactating Females:Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test at screening or by positive urine hCG test prior to dosing. Lactating females.
* Allergies: Milk Protein Allergy: History of severe milk protein allergy. Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the dry powder inhaler (DPI) (i.e., lactose or magnesium stearate). Historical Allergy: History of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
* 12-Lead ECG abnormality: Significant abnormality in the 12-lead electrocardiogram (ECG) performed at screening.
* Tobacco Use: Current smokers or a smoking history of \>=10 pack years. A subject may not have used any inhaled tobacco products in the 12 month period preceding the screening visit.
* Previous Participation: Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Primary outcomes:
measure: Change from baseline in FEV1 at 15, 30 minutes, 1, 2, 4, 12, 24, 36, 48, 60 and 72 hours post dose.
timeFrame: Baseline (pre dose) and 15, 30 minutes, 1, 2, 4, 12, 24, 36, 48, 60 and 72 hours post dose in each treatment period
Secondary outcomes:
measure: Time to onset of bronchodilator effect of FF/VI 100/25 mcg
timeFrame: Baseline, 15, 30 minutes, 1, 2, 4 hours post dose in each treatment period
Other outcomes:
Locations:
city: Wellington
country: New Zealand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: