Trial Outcomes & Findings for SERETIDE 100/50 bd (Twice Daily) Versus FLIXOTIDE 100 bd As Initial Maintenance Therapy In Moderate Asthma In Adults (NCT NCT00461500)

NCT ID: NCT00461500

Last Updated: 2017-03-03

Results Overview

Mini Wright Peak Flow Meter used to allow patients to monitor their asthma - Peak Flow (or PEF - peak expiratory flow) is a measurement of how fast you can blow out. When someone is well, their PEF is higher - when the airways are narrow (as in asthma), PEF is lower. Readings based on age, height and gender.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 81 participants
• Primary outcome timeframe: Baseline, Weeks 5-12
• Results posted on: 2017-03-03

Participant Flow

Participant milestones

Measure	SFC (Salmeterol Xinafoate/Fluticasone Propionate Combination) Analysis population are all randomized subjects in this arm. 50/100ug - one inhalation twice daily	FP (Fluticasone Propionate)100 Analysis population are all randomized subjects in this arm. 100ug - one inhalation twice daily
Overall Study STARTED	37	44
Overall Study COMPLETED	30	38
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Measure	SFC (Salmeterol Xinafoate/Fluticasone Propionate Combination) Analysis population are all randomized subjects in this arm. 50/100ug - one inhalation twice daily	FP (Fluticasone Propionate)100 Analysis population are all randomized subjects in this arm. 100ug - one inhalation twice daily
Overall Study Adverse Event	1	0
Overall Study Lack of Efficacy	0	1
Overall Study Expired Drug Treatment	1	1
Overall Study Study Stopped	1	2
Overall Study Drug Treatment Misuse	1	0
Overall Study No Longer Willing to Take Part in Study	1	0
Overall Study Lost to Follow-up	2	2

Baseline Characteristics

SERETIDE 100/50 bd (Twice Daily) Versus FLIXOTIDE 100 bd As Initial Maintenance Therapy In Moderate Asthma In Adults

Baseline characteristics by cohort

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=34 Participants Analysis population used in this arm is ITT (intent-to-treat) population (Randomised subjects who received at least one dose of study drug and with evaluation for at least one efficacy criteria).	FP 100: Fluticasone Propionate. n=43 Participants Analysis population used in this arm is ITT population(Randomised subjects who received at least one dose of study drug and with evaluation for at least one efficacy criteria).	Total n=77 Participants Total of all reporting groups
Age, Continuous	47.3 years STANDARD_DEVIATION 17.9 • n=5 Participants	49.3 years STANDARD_DEVIATION 19.3 • n=7 Participants	48.4 years STANDARD_DEVIATION 18.6 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	25 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Smoking Status Current Smoker	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Smoking Status Ex-Smoker	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Smoking Status Never Smoked	24 participants n=5 Participants	34 participants n=7 Participants	58 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 5-12

Population: Intent-to-Treat population are all randomized patients having received one study drug dose and had at least one complete efficacy assessment.

Mini Wright Peak Flow Meter used to allow patients to monitor their asthma - Peak Flow (or PEF - peak expiratory flow) is a measurement of how fast you can blow out. When someone is well, their PEF is higher - when the airways are narrow (as in asthma), PEF is lower. Readings based on age, height and gender.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=29 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=37 Participants 100ug - one inhalation twice daily
Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) Over Weeks 5-12	59.21 Liters per minute (L/min) Standard Deviation 70.42	50.98 Liters per minute (L/min) Standard Deviation 71.05

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Intent-to-Treat population.

FEV1 is the amount of air (in liters) you can blow out within one second. A spirometer is the device used to measure FEV1. With normal lungs and airways you can normally blow out most of the air from your lungs within one second. Age, height and gender is used to determine what is normal. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
Change From Baseline in Pre-dose FEV1 (Forced Expiratory Volume in One Second) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach)	0.25 Liters Standard Deviation 0.37	0.11 Liters Standard Deviation 0.35

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Intent-to-Treat population.

Percent predicted is based on tables of normal values that use variables such as age, gender, and weight as a method of standardization. Spirometry results are expressed as a percentage, and are generally considered abnormal if less than 80 percent of the normal predicted value. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
Change From Baseline in Pre-dose (Percent Predicted) FEV1 Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach)	7.46 Percentage predicted of FEV1 Standard Deviation 12.34	4.97 Percentage predicted of FEV1 Standard Deviation 13.07

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Intent-to-Treat population.

Reversibility is calculated as the percentage improvement of FEV1 from baseline. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable. Percent reversibility of FEV1 was calculated as follows: (Post-bronchodilator FEV1 - pre-bronchodilator FEV1)/pre-bronchodilator FEV1 x 100. A negative difference indicates less reversibility.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=41 Participants 100ug - one inhalation twice daily
Change From Baseline in FEV1 Reversibility Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach)	-9.46 Percent change Standard Deviation 16.47	-4.05 Percent change Standard Deviation 11.97

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Intent-to-Treat

FVC is the total amount of air that can forcibly be blown out after full inspiration, measured in liters. A spirometer is the device used to measure FVC. Age, height and gender is used to determine what is normal. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
Change From Baseline in Pre-dose Forced Expiratory Vital Capacity (FVC) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach)	0.18 Liters Standard Deviation 0.44	0.14 Liters Standard Deviation 0.49

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Intent-to-Treat population.

Forced Expiratory Flow 25-75% (measured by a spirometer) is the average flow (or speed) of air coming out of the lung during the middle portion of the expiration. Age, height, and gender is used to determine what is normal. Change from BL could have been measured at any time during the study (up to Week 12), using the LOCF (for each individual, missing values are replaced by the last observed value of that variable). Change from BL is measured as percentage of predicted value, with height, gender, age, and race as variables (percentage of predicted value at endpoint minus value at BL).

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
Change From Baseline (BL) in Pre-dose FEF 25-75% (Forced Expiratory Flow) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach)	7.24 Percentage of predicted value Standard Deviation 24.07	4.28 Percentage of predicted value Standard Deviation 17.30

SECONDARY outcome

Timeframe: 12-Week Treatment Period (Week 1 through Week 12)

Population: Intent-to-Treat population.

Subjects will record exacerbations (defined as temporary PEF decrease, increase in salbutamol use) in a Daily Record Card (DRC). The number of events are categorized as those that showed a deterioration in asthma requiring administration of oral corticosteroids and/or a deterioration in asthma requiring emergency room visit and/or hospitalization (hosp.).

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=34 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=43 Participants 100ug - one inhalation twice daily
Number of Participants With at Least One Exacerbation During 12-Week Treatment Period Exac. needing oral corticosteroids and/or hosp.	0 Participants	0 Participants
Number of Participants With at Least One Exacerbation During 12-Week Treatment Period Any exacerbation (Exac.)	1 Participants	5 Participants

SECONDARY outcome

Timeframe: Weeks 5 -12

Population: Intent-to-Treat population.

Well-controlled asthma is defined as 2 or more of the following: symptoms on no more than 2 days with symptom score of >1; no more than 2 days of rescue meds (maximum of 4 per week); >=80% predicted morning PEF. And no night time awakenings, exacerbations, emergency room visits, and treatment related adverse effects requiring a change to therapy. The number of participants who achieved "well-controlled" asthma at any time during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=29 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=35 Participants 100ug - one inhalation twice daily
Number of Participants Who Achieved Well-Controlled Asthma During Weeks 5-12 Yes	13 Participants	11 Participants
Number of Participants Who Achieved Well-Controlled Asthma During Weeks 5-12 No	16 Participants	24 Participants

SECONDARY outcome

Timeframe: Weeks 5 - 12

Population: Intent-to-Treat population.

Well-controlled asthma is defined as 2 or more of the following: symptoms on no more than 2 days with symptom score of >1; no more than 2 days of rescue meds (maximum of 4 per week); >=80% predicted morning PEF. And no night time awakenings, exacerbations, emergency room visits, and treatment related adverse effects requiring a change to therapy. The median number of weeks to first achieve "well-controlled" asthma during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=34 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=43 Participants 100ug - one inhalation twice daily
Median Number of Weeks to First Achieve Well-Controlled Asthma During Weeks 5-12	3.1 Weeks Interval 0.1 to 15.6	4.1 Weeks Interval 0.1 to 14.1

SECONDARY outcome

Timeframe: Weeks 5 - 12

Population: Intent-to-Treat population.

Totally-controlled asthma is defined as no daily symptoms, no night-time awakenings, no exacerbations, no rescue medication, no emergency visits, no treatment related adverse events resulting in change in asthma therapy, >=80% predicted PEF. The number of subjects who achieved "total-controlled" asthma at any time during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=29 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=36 Participants 100ug - one inhalation twice daily
Number of Participants Who Achieved Total-controlled Asthma During Weeks 5-12 Yes	1 Participants	1 Participants
Number of Participants Who Achieved Total-controlled Asthma During Weeks 5-12 No	28 Participants	35 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-Treat population.

5 question test with various responses rating frequency of asthma events over 4-week period. Questions include occurrence of asthma affecting work/school; causing shortness of breath; symptoms (wheezing, coughing, shortness of breath, chest tightness, pain) wake you up at night; causing need for rescue medication; asthma control. Scale: 1=all of time, 2=most of time, 3=some of the time, 4=a little of the time, 5=none of the time. Possible ACT scores range from 5 to 25.

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
Change From Baseline in Asthma Control Test (ACT) Score at Week 12	5.64 Score on a scale Standard Deviation 5.00	5.90 Score on a scale Standard Deviation 4.81

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-Treat population.

Score is ranged from 5 (poor control) to 25 (complete control).

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=42 Participants 100ug - one inhalation twice daily
ACT Score in Classes at Week 12 < 15 score	5 Particpants	2 Particpants
ACT Score in Classes at Week 12 15-19 score	12 Particpants	15 Particpants
ACT Score in Classes at Week 12 >=20 score	16 Particpants	25 Particpants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-Treat population.

7-point scale where 1=total impairment and 7=no impairment. Questions contain 32 items in four domains. Domains include Activity Limitation (11 items), Symptoms (12 items), Emotional Function (5 items), and Environmental Stimuli (4 items). 32 items produce one overall quality of life score. The 7 points scoring are different and depend on the item : they are the translation in French of the original questionnaire from Juniper. Possible AQLQ scores range from 1 to 7 (the mean of all the questions).

Outcome measures

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=33 Participants 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=41 Participants 100ug - one inhalation twice daily
Change From Baseline in Overall Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12	0.99 Score on a scale Standard Deviation 0.92	1.11 Score on a scale Standard Deviation 1.02

Adverse Events

SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

FP 100: Fluticasone Propionate

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	SFC 100: Salmeterol Xinafoate/Fluticasone Propionate Combined n=37 participants at risk 50/100ug - one inhalation twice daily	FP 100: Fluticasone Propionate n=44 participants at risk 100ug - one inhalation twice daily
Infections and infestations Bronchitis	0.00% 0/37	4.5% 2/44 • Number of events 2

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centres of a multi-centre trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER