Study Of Fluticasone Propionate/Salmeterol In Asthmatic Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00517634
• Collaborator: (none)
• Enrollment: 23
• Locations: 2
• Arms: 6
• Duration (Months): 11
• Patients Per Site: 11.5
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The aim of the present study is to investigate whether the effects of salmeterol in combination with fluticasone propionate on blood markers of airway inflammation are maintained after chronic dosing and whether the effect is influenced by the time of allergen challenge relative to the time of dosing.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: FP; Drug: SFC; Drug: Placebo	Phase 4

Detailed Description

A 12-week, randomised, double-blind, placebo-controlled, three-period, cross-over pilot study comparing the effect of salmeterol/fluticasone propionate, fluticasone propionate and placebo on perpheral blood eosinophils and serum IL-5 in response to allergen challenge in asthma subjects when allergen challenge is administered at 1 hour or 11-12 hours post-dose of the dosing interval

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-week, Randomised, Double-blind, Placebo-controlled, Three-period, Cross-over Pilot Study Comparing the Effect of Salmeterol/Fluticasone Propionate, Fluticasone Propionate and Placebo on Perpheral Blood Eosinophils and Serum IL-5 in Response to Allergen Challenge in Asthma Subjects When Allergen Challenge is Administered at 1 Hour or 11-12 Hours Post-dose of the Dosing Interval
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1: FP, SFC, Placebo Fluticasone Propionate (FP) 100 micrograms (mcg) twice daily (BID) in the first treatment period: Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID in the second treatment period: Placebo in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo
Experimental: Sequence 2: Placebo, SFC, FP Placebo in the first treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo
Experimental: Sequence 3: SFC, FP, Placebo Salmeterol/Fluticasone Propionate 50/100 Combination mcg BID in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Placebo in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo
Experimental: Sequence 4: SFC, Placebo, FP Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the first treatment period: Placebo in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo
Experimental: Sequence 5: FP, Placebo, SFC Fluticasone Propionate 100 mcg BID in the first treatment period: Placebo in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo
Experimental: Sequence 6: Placebo, FP, SFC Placebo in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period	Drug: FP; Fluticasone Propionate 100 mcg BD; Drug: SFC; Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD; Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 [0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35]

   Number of peripheral blood eosinophils measured from blood draws

Secondary Outcome Measures

1. Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 [0-6 hours, post allergen challenge, 1 hour post treatment, Day 14]

   Number of peripheral blood eosinophils measured from blood draws

2. Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 35 [0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35]

   Amount of serum interleukin (IL)-5 measured from blood draws

3. Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 14 [0-6 hours post allergen challenge, 1 hour after dosing, Day 14]

   Amount of serum IL-5 measured from blood draws

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent.

• Outpatient.

• Male or non-pregnant/non-lactating female.

• Aged 18-55.

• Diagnosis of asthma.

• Pre-bronchodilatory FEV1 > 75% predicted.

• Using inhaled short-acting beta-2-agonists (SABA) with no inhaled corticosteroids.

• Judged capable of withholding SABA for at least 6 hours prior to visits.

• Reversibility of >12% and 200mL or PC20 of <8mg/mL.

• Demonstration of atopy

Exclusion Criteria:

• History of life-threatening asthma.

• Use of proscribed asthma medications.

• Use of anti-histamines or potent inhibitors of CYP3A4.

• Respiratory tract infection.

• Asthma exacerbation with 4 weeks of Visit 1.

• Subjects with exercise induced asthma only.

• Concurrent respiratory disease.

• Other clinically significant, uncontrolled condition or disease.

• Use of any investigational drug within 30 days.

• Allergic to beta-2-agonists, inhaled corticosteroids or excipients.

• Positive pregnancy test.

• Using immunosuppressive medications.

• Milk protein allergy.

• Factors likely to interfere with attendance.

• Current smokers or ex-smokers with a history of >10 pack years.

• Affiliation wih Investigator site.

• Medications that may affect the course of asthma or interact with sympathomimetic amines.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Madison	Wisconsin	United States	53792
2	GSK Investigational Site	Manchester		United Kingdom	M23 9QZ

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00517634
• Other Study ID Numbers: HZA109912
• First Posted: Aug 17, 2007
• Last Update Posted: Dec 16, 2016
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: asthma; allergen challenge; IL-5; eosinophils
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Arm/Group Title	Sequence 1: FP, SFC, Placebo	Sequence 2: Placebo, SFC, FP	Sequence 3: SFC, FP, Placebo	Sequence 4: SFC, Placebo, FP	Sequence 5: FP, Placebo, SFC	Sequence 6: Placebo, FP, SFC
Arm/Group Description	Fluticasone Propionate (FP) 100 micrograms (mcg) twice daily (BID) in the first treatment period: Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID in the second treatment period: Placebo in the third treatment period	Placebo in the first treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period	Salmeterol/Fluticasone Propionate 50/100 Combination mcg BID in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Placebo in the third treatment period	Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the first treatment period: Placebo in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period	Fluticasone Propionate 100 mcg BID in the first treatment period: Placebo in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period	Placebo in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period
Period Title: First Treatment Period
STARTED	4	4	4	3	4	4
COMPLETED	4	4	4	3	4	4
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Treatment Period
STARTED	4	4	4	3	4	4
COMPLETED	4	4	4	3	3	4
NOT COMPLETED	0	0	0	0	1	0
Period Title: First Treatment Period
STARTED	4	4	4	3	3	4
COMPLETED	4	4	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study Population
Arm/Group Description	Overall Study Population: participants in all three treatment periods
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.6 (6.63)
Gender (Count of Participants)
Female	9 39.1%
Male	14 60.9%
Race/Ethnicity, Customized (participants) [Number]
African American	2 8.7%
Caucasian	21 91.3%

Outcome Measures

1. Primary Outcome

Title	Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35
Description	Number of peripheral blood eosinophils measured from blood draws
Time Frame	0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants receiving at least one dose of study medication who had at least one post-randomization efficacy assessment

Arm/Group Title	Placebo	FP 100 mcg BID	SFC 50/100 mcg BID
Arm/Group Description	Placebo	Fluticasone Propionate (FP) 100 mcg BID	Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID
Measure Participants	22	22	22
Mean (95% Confidence Interval) [Giga Units per Liter (GI/L)]	-0.050	-0.040	-0.023

2. Secondary Outcome

Title	Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14
Description	Number of peripheral blood eosinophils measured from blood draws
Time Frame	0-6 hours, post allergen challenge, 1 hour post treatment, Day 14

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	FP 100 mcg BID	SFC 50/100 mcg BID
Arm/Group Description	Placebo	Fluticasone Propionate (FP) 100 mcg BID	Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID
Measure Participants	21	23	20
Mean (95% Confidence Interval) [Giga Units per Liter (GI/L)]	-0.023	-0.022	-0.013

3. Secondary Outcome

Title	Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 35
Description	Amount of serum interleukin (IL)-5 measured from blood draws
Time Frame	0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 14
Description	Amount of serum IL-5 measured from blood draws
Time Frame	0-6 hours post allergen challenge, 1 hour after dosing, Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Placebo		FP 100 mcg BID		SFC 50/100 BID
Arm/Group Description	Placebo		Fluticasone Propionate 100 mcg BID		Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID
All Cause Mortality
	Placebo		FP 100 mcg BID		SFC 50/100 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		FP 100 mcg BID		SFC 50/100 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Infections and infestations
Appendicitis	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	Placebo		FP 100 mcg BID		SFC 50/100 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/22 (63.6%)		16/23 (69.6%)		10/22 (45.5%)
Blood and lymphatic system disorders
Lymphadenopathy	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Eye disorders
Eye pruritus	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Gastrointestinal disorders
Diarrhea	1/22 (4.5%)		1/23 (4.3%)		0/22 (0%)
Nausea	1/22 (4.5%)		1/23 (4.3%)		0/22 (0%)
Abdominal pain upper	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Toothache	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
General disorders
Chest discomfort	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Discomfort	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Immune system disorders
Hypersensitivity	0/22 (0%)		1/23 (4.3%)		1/22 (4.5%)
Multiple allergies	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
House dust allergy	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Infections and infestations
Nasopharyngitis	2/22 (9.1%)		3/23 (13%)		2/22 (9.1%)
Sinusitis	0/22 (0%)		1/23 (4.3%)		1/22 (4.5%)
Appendicitis	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Candidiasis	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Lower respiratory tract infection	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Tooth abscess	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Injury, poisoning and procedural complications
Periorbital haematoma	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Muscle strain	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Post procedural complication	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Tendonitis	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Nervous system disorders
Headache	7/22 (31.8%)		3/23 (13%)		2/22 (9.1%)
Nerve compression	1/22 (4.5%)		0/23 (0%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolarngeal Pain	1/22 (4.5%)		2/23 (8.7%)		2/22 (9.1%)
Throat irritation	1/22 (4.5%)		2/23 (8.7%)		0/22 (0%)
Dry Throat	0/22 (0%)		1/23 (4.3%)		1/22 (4.5%)
Productive cough	0/22 (0%)		1/23 (4.3%)		1/22 (4.5%)
Rhinorrhea	1/22 (4.5%)		0/23 (0%)		1/22 (4.5%)
Dysphonia	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Dyspnoea	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Pharyngeal disorder	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Sinus congestion	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Sneezing	0/22 (0%)		1/23 (4.3%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Rash	0/22 (0%)		0/23 (0%)		1/22 (4.5%)
Surgical and medical procedures
Tooth extraction	0/22 (0%)		1/23 (4.3%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.