A Randomized, Blinded, Parallel Group, Placebo-Controlled, Multiple Dose, Multicenter, Multinational Study to Compare the Therapeutic Equivalence of a Budesonide 80 μg/Formoterol Fumarate Dihydrate 4.5 μg Inhalation Aerosol (Manufactured by Catalent for Watson Laboratories Inc.) to Symbicort® (Budesonide 80 μg/Formoterol Fumarate Dihydrate 4.5 μg Inhalation Aerosol) (Manufactured by AstraZeneca) in Adolescent and Adult Patients With Asthma
Overview
- Phase
- Phase 3
- Intervention
- Generic Budesonide/Formoterol Fumarate Dihydrate
- Conditions
- Asthma
- Sponsor
- Actavis Inc.
- Enrollment
- 1714
- Locations
- 17
- Primary Endpoint
- Equivalence Analysis of Area Under the Serial FEV1-Time Effect Curve From Time 0 to 12 Hours (FEV1 Area Under Curve [AUC0-12]) on the First Day of Treatment
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study has a randomized multiple-dose, placebo-controlled, parallel group design consisting of a 2-week open placebo Run-in Period followed by a 6-week Treatment Period with placebo, test product (budesonide 80 microgram [μg]/formoterol fumarate dihydrate 4.5 μg), or reference product (Symbicort® inhalation aerosol).
Detailed Description
This is a pivotal trial that will examine the therapeutic equivalence of a new generic fixed-dose combination product containing budesonide 80 μg/formoterol fumarate dihydrate 4.5 μg and reference listed drug (RLD) Symbicort® inhalation aerosol in adult participants with chronic but stable asthma as defined in National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP 3) guidelines. To ensure adequate study sensitivity, the test and reference products should both be statistically superior to placebo (p\<0.05) with regard to the bioequivalent study primary endpoints. Participants will be provided a generic placebo pressurized metered-dose inhaler (pMDI) device for use during the 2-week Run-in Period for device training.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Generic Budesonide/Formoterol Fumarate Dihydrate
After a 2-week Run-in Period of administering 2 inhalations twice daily via a generic placebo pMDI device, participants will administer 2 inhalations twice daily via a generic budesonide/formoterol fumarate dihydrate (80 μg/4.5 μg) pMDI for up to 50 days.
Intervention: Generic Budesonide/Formoterol Fumarate Dihydrate
Symbicort (Budesonide/Formoterol Fumarate Dihydrate)
After a 2-week Run-in Period of administering 2 inhalations twice daily via a generic placebo pMDI device, participants will administer 2 inhalations twice daily via a Symbicort budesonide/formoterol fumarate dihydrate (80 μg/4.5 μg) pMDI for up to 50 days.
Intervention: Symbicort® (Budesonide/Formoterol Fumarate Dihydrate)
Placebo
After a 2-week Run-in Period of administering 2 inhalations twice daily via a generic placebo pMDI device, participants will administer 2 inhalations twice daily via a generic placebo pMDI for up to 50 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Equivalence Analysis of Area Under the Serial FEV1-Time Effect Curve From Time 0 to 12 Hours (FEV1 Area Under Curve [AUC0-12]) on the First Day of Treatment
Time Frame: 0 to 12 hours on Day 1
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis.
Superiority Analysis of Area Under the Serial FEV1-Time Effect Curve From Time 0 to 12 Hours (FEV AUC0-12) on the First Day of Treatment
Time Frame: 0 to 12 hours on Day 1
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis.
Equivalence Analysis of Baseline-Adjusted Average Predose FEV1 at End of Treatment
Time Frame: Day 1 up to Day 50
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit \[up to Day 50\]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: \[FEV1 at end of treatment\] - \[Baseline FEV1\].
Superiority Analysis of Baseline-Adjusted Average Predose FEV1 at End of Treatment
Time Frame: Day 1 up to Day 50
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit \[up to Day 50\]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: \[FEV1 at end of treatment\] - \[Baseline FEV1\].