Trial Outcomes & Findings for A Non-inferiority Study to Evaluate Efficacy, Safety and Tolerability of NEUMOTEROL® 400 and SYMBICORT® Forte in Adults With Asthma (NCT NCT02233803)
NCT ID: NCT02233803
Last Updated: 2017-09-15
Results Overview
FEV1 is maximal amount of air, forcefully exhaled in one second. Trough FEV1 is defined as morning prebronchodilator and predose: 12 hours (h) after last evening dose D28 at end of each TP. Measured by spirometer in morning, before using bronchodilator and pre-dosing at wk1 D1 and wk4 D29 of each TP and test was performed within 30 minutes prior to dosing. Change from BL was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific (PS) BL, treatment group and period, with participant as random effect. PS BL value is pre-dose assessment collected on D1 of each TP. SL BL is arithmetic mean of PS BL values of participant. If only one of PS BL value is missing for participant, SL BL took value of other BL. If both PS BL values were missing, SL BL was set to missing. Period level BL=PS BL - associated SL BL.
COMPLETED
PHASE4
239 participants
BL (D1) and D29 (each TP)
2017-09-15
Participant Flow
The study was conducted in adult asthma participants, at 11 centres in Argentina from 14 November 2014 to 11 December 2015.
Total 6 phases of study; pre-screening, screening/run-in, treatment period (TP) 1 washout, TP2, and follow-up. Out of total 239 enrolled participants, only 199 participants were randomized. 29 were screen failures and 10 were Run-in failures. One participant not randomized as the target number of participants for study was reached
Participant milestones
| Measure |
NEUMOTEROL 400/ SYMBICORT FORTE
During TP1, participants received Regimen A where the eligible participants received, 1 inhalation of budesonide/formoterol fumarate (BFF), 400/12 microgram \[mcg\] (NEUMOTEROL 400) by single capsule inhaler each morning and evening for 4- weeks (Wks). This was followed by a wash out period of 4 Wks , during which all the participants received budesonide DPI 400 mcg (NEUMOTEX 400) twice daily. The wash-out period was followed by Regimen B during which the eligible participants took, 1 inhalation of BFF 320/9 mcg (SYMBICORT FORTE), by turbuhaler inhaler each morning and evening, for 4-Wks. Additionally all participants were allowed to take rescue medication (salbutamol 100 mcg) during the study.
|
SYMBICORT FORTE/ NEUMOTEROL 400
During TP1, the participants received Regimen B where the eligible participants took, 1 inhalation of BFF 320/9 mcg (SYMBICORT FORTE), by turbuhaler inhaler each morning and evening for 4-Wks. This was followed by a wash out period of 4 Wks, during which all the participants received budesonide DPI 400 mcg (NEUMOTEX 400) twice daily. It was then followed by Regimen A during which eligible participants received, 1 inhalation of NEUMOTEROL 400 by single capsule inhaler each morning and evening, for 4-Wks. Additionally all participants were allowed to take rescue medication (salbutamol 100 mcg) during the study.
|
|---|---|---|
|
Treatment Period 1 (4-Wks)
STARTED
|
100
|
99
|
|
Treatment Period 1 (4-Wks)
COMPLETED
|
97
|
95
|
|
Treatment Period 1 (4-Wks)
NOT COMPLETED
|
3
|
4
|
|
Washout Period (4-Wks)
STARTED
|
97
|
95
|
|
Washout Period (4-Wks)
COMPLETED
|
95
|
93
|
|
Washout Period (4-Wks)
NOT COMPLETED
|
2
|
2
|
|
Treatment Period 2 (4-Wks)
STARTED
|
95
|
93
|
|
Treatment Period 2 (4-Wks)
COMPLETED
|
93
|
91
|
|
Treatment Period 2 (4-Wks)
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
NEUMOTEROL 400/ SYMBICORT FORTE
During TP1, participants received Regimen A where the eligible participants received, 1 inhalation of budesonide/formoterol fumarate (BFF), 400/12 microgram \[mcg\] (NEUMOTEROL 400) by single capsule inhaler each morning and evening for 4- weeks (Wks). This was followed by a wash out period of 4 Wks , during which all the participants received budesonide DPI 400 mcg (NEUMOTEX 400) twice daily. The wash-out period was followed by Regimen B during which the eligible participants took, 1 inhalation of BFF 320/9 mcg (SYMBICORT FORTE), by turbuhaler inhaler each morning and evening, for 4-Wks. Additionally all participants were allowed to take rescue medication (salbutamol 100 mcg) during the study.
|
SYMBICORT FORTE/ NEUMOTEROL 400
During TP1, the participants received Regimen B where the eligible participants took, 1 inhalation of BFF 320/9 mcg (SYMBICORT FORTE), by turbuhaler inhaler each morning and evening for 4-Wks. This was followed by a wash out period of 4 Wks, during which all the participants received budesonide DPI 400 mcg (NEUMOTEX 400) twice daily. It was then followed by Regimen A during which eligible participants received, 1 inhalation of NEUMOTEROL 400 by single capsule inhaler each morning and evening, for 4-Wks. Additionally all participants were allowed to take rescue medication (salbutamol 100 mcg) during the study.
|
|---|---|---|
|
Treatment Period 1 (4-Wks)
Protocol-defined stopping criteria reach
|
1
|
0
|
|
Treatment Period 1 (4-Wks)
Adverse Event
|
0
|
1
|
|
Treatment Period 1 (4-Wks)
Protocol Violation
|
2
|
2
|
|
Treatment Period 1 (4-Wks)
Withdrawal by Subject
|
0
|
1
|
|
Washout Period (4-Wks)
Lost to Follow-up
|
0
|
1
|
|
Washout Period (4-Wks)
Physician Decision
|
1
|
0
|
|
Washout Period (4-Wks)
Withdrawal by Subject
|
1
|
1
|
|
Treatment Period 2 (4-Wks)
Lost to Follow-up
|
1
|
0
|
|
Treatment Period 2 (4-Wks)
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
A Non-inferiority Study to Evaluate Efficacy, Safety and Tolerability of NEUMOTEROL® 400 and SYMBICORT® Forte in Adults With Asthma
Baseline characteristics by cohort
| Measure |
Total
n=199 Participants
The eligible participants were randomised to receive either Regimen A in TP1 and Regimen B in TP2, or Regimen B in TP1 and Regimen A in TP2 according to the randomisation schedule. Both the TPs were separated by a wash out period of 4 weeks. Regimen A: 1 inhalation of budesonide/formoterol fumarate (BFF), 400/12 microgram \[mcg\] (NEUMOTEROL 400) by single capsule inhaler each morning and evening. Regimen B: 1 inhalation of BFF 320/9 mcg (SYMBICORT FORTE) by turbuhaler inhaler each morning and evening. Additionally all participants were allowed to take rescue medication (salbutamol 100 mcg) during the study.
|
|---|---|
|
Age, Continuous
|
46.2 Years
STANDARD_DEVIATION 15.26 • n=5 Participants
|
|
Sex: Female, Male
Female
|
142 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
57 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian/European Heritage
|
199 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: BL (D1) and D29 (each TP)Population: The intent to treat (ITT) population comprised of all randomized participants who received at least one dose of study treatment. This population was based on the treatment to which the participant was randomized. Only those participants with data available at the indicated time points were analyzed.
FEV1 is maximal amount of air, forcefully exhaled in one second. Trough FEV1 is defined as morning prebronchodilator and predose: 12 hours (h) after last evening dose D28 at end of each TP. Measured by spirometer in morning, before using bronchodilator and pre-dosing at wk1 D1 and wk4 D29 of each TP and test was performed within 30 minutes prior to dosing. Change from BL was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific (PS) BL, treatment group and period, with participant as random effect. PS BL value is pre-dose assessment collected on D1 of each TP. SL BL is arithmetic mean of PS BL values of participant. If only one of PS BL value is missing for participant, SL BL took value of other BL. If both PS BL values were missing, SL BL was set to missing. Period level BL=PS BL - associated SL BL.
Outcome measures
| Measure |
NEUMOTEROL 400
n=188 Participants
Eligible participants received NEUMOTEROL 400 during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pressurized metered dose inhaler (pMDI), as rescue medication.
|
SYMBICORT FORTE
n=188 Participants
Eligible participants received Symbicort forte during TP1 or TP2 as per their randomization . The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
|---|---|---|
|
Change From Baseline (BL) in Trough Morning Forced Expiratory Volume in One Second (FEV1) at Day (D)29
|
0.194 Litre (L)
Standard Error 0.0213
|
0.150 Litre (L)
Standard Error 0.0213
|
SECONDARY outcome
Timeframe: (0-10 h) at D1 (each TP)Population: ITT population. Only those participants with data available at the indicated time points were analyzed.
FEV1 is the maximal amount of air that can be forcefully exhaled in one second. FEV1 AUC (0 to 10h) was measured at beginning of each TP. AUC was derived using values observed at the following timepoints: 0 minute (pre-morning dosing), 5 minutes (m), 15m, 30m, 1, 2, 5, and 10h; post morning dosing FEV1 values on D1 of each TP. Pre-dose was taken as, 0h timepoint on the visit of interest, and all subsequent timepoints were calculated relative to that timepoint. FEV1 AUC was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific(PS) BL, treatment group and period, with participant as random effect.
Outcome measures
| Measure |
NEUMOTEROL 400
n=193 Participants
Eligible participants received NEUMOTEROL 400 during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pressurized metered dose inhaler (pMDI), as rescue medication.
|
SYMBICORT FORTE
n=194 Participants
Eligible participants received Symbicort forte during TP1 or TP2 as per their randomization . The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
|---|---|---|
|
FEV1 Area Under the Curve (AUC) (0-10 h) at D1 of Each TP
|
24.573 L*hrs
Standard Error 0.1840
|
23.593 L*hrs
Standard Error 0.1836
|
SECONDARY outcome
Timeframe: BL up to W4 (each TP)Population: ITT population. Only those participants with data available at the indicated time points were analyzed.
ACT was basically a five item questionnaire, to measure participant's asthma control. It comprised of five possible answers to each question, associated with a score of 1 to 5 (1=poor control and 5=good control), wherein the scores from each question were summed to give an overall score (5=poor control and 25=complete control). ACT was recommended during each visit and was completed by the participant before any procedures were performed, avoiding any influence of the participants response. Change from BL was analysed using mixed effects ANCOVA model fitting terms for subject-level (SL) BL, Adjusted period-specific(PS) BL, treatment group and period, with participant as random effect. PS BL value, is pre-dose assessment collected on D1 of each TP. SL BL, is arithmetic mean of PS BL values of participant. Participants with an ACT below 15 were excluded from the study.
Outcome measures
| Measure |
NEUMOTEROL 400
n=188 Participants
Eligible participants received NEUMOTEROL 400 during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pressurized metered dose inhaler (pMDI), as rescue medication.
|
SYMBICORT FORTE
n=188 Participants
Eligible participants received Symbicort forte during TP1 or TP2 as per their randomization . The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
|---|---|---|
|
Change From BL in Asthma Control Test (ACT) at 4 Wks for Each TP
|
1.6 units on scale
Standard Error 0.20
|
1.0 units on scale
Standard Error 0.20
|
Adverse Events
NEUMOTEROL 400
SYMBICORT FORTE
Serious adverse events
| Measure |
NEUMOTEROL 400
n=193 participants at risk
Eligible participants received NEUMOTEROL 400 during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
SYMBICORT FORTE
n=194 participants at risk
Eligible participants received Symbicort forte during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
|---|---|---|
|
Hepatobiliary disorders
Cholelithiasis
|
0.52%
1/193 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
0.00%
0/194 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/193 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
0.52%
1/194 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
Other adverse events
| Measure |
NEUMOTEROL 400
n=193 participants at risk
Eligible participants received NEUMOTEROL 400 during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
SYMBICORT FORTE
n=194 participants at risk
Eligible participants received Symbicort forte during TP1 or TP2 as per their randomization. The TPs were separated by washout period of 4-wks during which participants received NEUMOTEX 400, twice daily. The participants were allowed to take salbutamol 100mcg pMDI, as rescue medication.
|
|---|---|---|
|
Nervous system disorders
Headache
|
5.2%
10/193 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
5.7%
11/194 • Up to 14 wks
Safety population comprised of all participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received.
|
Additional Information
GSK Response Center
GlaxoSmithKline
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 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.
- Publication restrictions are in place
Restriction type: OTHER