NCT01687283

Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma

Completed Phase 3 Results posted Last updated 11 October 2018

What this trial tests

Phase 3 trial testing fluticasone propionate inhalation solution in Asthma in 316 participants. Completed in 7 November 2013.

Timeline

27 September 2012

Primary endpoint
7 November 2013

7 November 2013

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	316
Start date	27 September 2012
Primary completion	7 November 2013
Estimated completion	7 November 2013
Sites	25 locations across China

Drugs / interventions tested

• fluticasone propionate inhalation solution
• budesonide suspension

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 17 to 70, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population Primary · Baseline (Visit 2) and up to Week 12

The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis

Group	Value	95% CI
FP 1 mg BID	12.71	± 3.677
BUD 2 mg BID	14.51	± 3.714

Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population Primary · Baseline (Visit 2) and up to Week 12

The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis

Group	Value	95% CI
FP 1 mg BID	13.50	± 3.806
BUD 2 mg BID	15.78	± 3.750

Mean Change of Evening PEF From Baseline Over 12 Weeks Secondary · Baseline (Visit 2) and up to Week 12

The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the evening PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily PM PEF averaged over the 12-weeks treatment period.

Group	Value	95% CI
FP 1 mg BID	12.39	± 3.469
BUD 2 mg BID	15.16	± 3.504

Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks Secondary · Baseline (Visit 2) and over 12 Weeks

While calculating symptom-free 24-hour periods, a given 24-hour period was set to be "symptom free" only if the participant's responses to both the morning and evening assessments indicated no symptoms. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. Change from Baseline was calculated as the difference between the value of the endpoint at the time point of interest and the baseline value. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.

Group	Value	95% CI
FP 1 mg BID	21.77	± 2.340
BUD 2 mg BID	21.15	± 2.364

Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks Secondary · Over 12 Weeks

Participants recorded day-time symptom score every day in the morning and evening at bedtime before taking any rescue or study medication and before PEF measurement, using 6 point scale on Diary Card indicating 0 = No symptoms during the day and 5 =Symptoms so severe that participant could not go to work or perform normal daily activities. Night time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.

Median day-time symptom score

Group	Value	95% CI
FP 1 mg BID	1.0	0 – 4
BUD 2 mg BID	1.0	0 – 4

Median night-time symptom score

Group	Value	95% CI
FP 1 mg BID	1.0	0 – 2
BUD 2 mg BID	1.0	0 – 3

Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks Secondary · Baseline and over 12 weeks

While calculating rescue-free 24-hour periods, the 24-hour period was only set to be "rescue free" if responses to both the morning and evening, assessments indicated no use of rescue medication. If there were symptoms in either the morning or the evening then that 24-hour period was set to as "not symptom free". Similarly, if there was rescue medication use in either the morning or the evening, then that 24-hour period was set to as "not rescue free". The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The value provide

Group	Value	95% CI
FP 1 mg BID	19.27	± 2.595
BUD 2 mg BID	24.01	± 2.612

Median Number of Times Rescue Medication Use Over 12 Weeks Secondary · Up to week 12

Participants recorded the number of inhalations of rescue salbutamol inhalation aerosol used during the day and night. The baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The analysis only included participants who had at least 2 days of non-missing numbers of times rescue medication (including zero) after randomization.

Group	Value	95% CI
FP 1 mg BID	0.0	0 – 7
BUD 2 mg BID	0.0	0 – 4

Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks Secondary · Baseline and at Week 2, 4, 8 and 12

FEV1 as a measure of lung function assessment was measured at Week 2, 4, 8 and 12. FEV1 measures were performed electronically by spirometry. The highest of three technically acceptable measurements was recorded. FEV1 was measured prior to study drug administration and any rescue salbutamol use. Baseline value was the assessment at Visit 2.Change from baseline was calculated as the value at the specific time point minus baseline value.

Week 2

Group	Value	95% CI
FP 1 mg BID	0.122	± 0.0283
BUD 2 mg BID	0.161	± 0.0281

Week 4

Group	Value	95% CI
FP 1 mg BID	0.187	± 0.0333
BUD 2 mg BID	0.195	± 0.0328

Week 8

Group	Value	95% CI
FP 1 mg BID	0.175	± 0.0314
BUD 2 mg BID	0.201	± 0.0309

Week 12

Group	Value	95% CI
FP 1 mg BID	0.217	± 0.0342
BUD 2 mg BID	0.200	± 0.0336

Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax) Secondary · Pre-dose, 0.5 hour (h), 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2

Tmax is defined as the time to maximum observed plasma concentration. Blood Pharmacokinetic (PK) samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of the last dose.

Group	Value	95% CI
FP 1 mg BID	0.905	± 59.9

Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax) Secondary · Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2

Cmax was defined as maximum observed plasma concentration. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.

Group	Value	95% CI
FP 1 mg BID	59.24	± 115.0

Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-area Under the Plasma Concentration-time Curve for the Dose Interval [AUC (0-τ)] Secondary · Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2

AUC (0-τ) was defined as the area under the plasma concentration-time curve for the dose interval. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.

Group	Value	95% CI
FP 1 mg BID	403.0958	± 70.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 12. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FP 1 mg BID

Serious: 4/158 (3%)

Deaths: 1/158

BUD 2 mg BID

Serious: 2/157 (1%)

Deaths: 0/157

Serious adverse events (5 terms)

Reaction	System	FP 1 mg BID	BUD 2 mg BID
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Infection	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Spondylolisthesis	Musculoskeletal and connective tissue disorders	—	—
Nephrotic syndrome	Renal and urinary disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	FP 1 mg BID	BUD 2 mg BID
Nasopharyngitis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—

Most-reported serious reactions: Asthma, Infection, Lung infection, Spondylolisthesis, Nephrotic syndrome.

Data from ClinicalTrials.gov NCT01687283 adverse events section.

Sponsor's own description

This is a multicentre, randomized, single-blind, active-controlled, parallel-group phase III local registration study for a treatment period of 12 weeks. This study aims to assess the effectiveness and safety of fluticasone propionate 1mg via nebulizer BID in treatment of Chinese adult and adolescent patients with severe persistent asthma for a treatment period of 12 weeks versus budesonide 2mg via nebulizer BID. The steady-state plasma pharmacokinetics of fluticasone propionate inhalation solution will also be assessed.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.