Trial Outcomes & Findings for Therapeutic Equivalence of Two Formulations of Fluticasone Propionate and Salmeterol Inhalation Powder in Subjects With Asthma (NCT NCT03756883)

Last Updated: 2021-09-24

Results Overview

Baseline-adjusted area under the serial FEV1-time curve calculated from time zero to 12 hours (AUC0-12h) on Day 1 of treatment. LSMeans will be used for the statistical analysis. Only the active treatments (test and reference) are compared in this analysis. The placebo arm was used in superiority analysis only.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

999 participants

Primary outcome timeframe

12 hours

Results posted on

2021-09-24

Participant Flow

The protocol included a minimum 14-day washout of all pre-study medication prior to assignment in the randomized treatment phase of the study.

Participant milestones

Participant milestones
Measure	Test Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Overall Study STARTED	485	413	101
Overall Study COMPLETED	472	402	94
Overall Study NOT COMPLETED	13	11	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Test Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Overall Study Adverse Event	2	2	2
Overall Study Lack of Efficacy	0	1	2
Overall Study Lost to Follow-up	3	3	0
Overall Study Protocol Violation	2	0	1
Overall Study Significant Worsening of Condition requiring Therapy	0	0	2
Overall Study Withdrawal by Subject	4	1	0
Overall Study Other Reasons	2	4	0

Baseline Characteristics

Therapeutic Equivalence of Two Formulations of Fluticasone Propionate and Salmeterol Inhalation Powder in Subjects With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Test n=485 Participants Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=413 Participants ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo n=101 Participants Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily	Total n=999 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 16.01 • n=5 Participants	45.2 years STANDARD_DEVIATION 16.87 • n=7 Participants	48.1 years STANDARD_DEVIATION 16.91 • n=5 Participants	45.7 years STANDARD_DEVIATION 16.60 • n=4 Participants
Sex: Female, Male Female	305 Participants n=5 Participants	251 Participants n=7 Participants	60 Participants n=5 Participants	616 Participants n=4 Participants
Sex: Female, Male Male	180 Participants n=5 Participants	162 Participants n=7 Participants	41 Participants n=5 Participants	383 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	191 Participants n=5 Participants	158 Participants n=7 Participants	37 Participants n=5 Participants	386 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	294 Participants n=5 Participants	255 Participants n=7 Participants	64 Participants n=5 Participants	613 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Black or African American	79 Participants n=5 Participants	70 Participants n=7 Participants	14 Participants n=5 Participants	163 Participants n=4 Participants
Race (NIH/OMB) White	395 Participants n=5 Participants	331 Participants n=7 Participants	84 Participants n=5 Participants	810 Participants n=4 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Asthma History (years)	29.2 years STANDARD_DEVIATION 15.87 • n=5 Participants	30.4 years STANDARD_DEVIATION 16.50 • n=7 Participants	32.6 years STANDARD_DEVIATION 17.09 • n=5 Participants	30.7 years STANDARD_DEVIATION 16.49 • n=4 Participants

PRIMARY outcome

Timeframe: 12 hours

Population: Per-Protocol Population that completed the serial assessments on Day 1 of treatment.

Outcome measures

Outcome measures
Measure	Test n=451 Participants Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=379 Participants ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Baseline-adjusted Area Under the Serial FEV1-time Curve Calculated From Time Zero to 12 Hours (AUC0-12h) on Day 1 of Treatment	4.03 liters x hours Standard Error 0.17	3.96 liters x hours Standard Error 0.18	—

PRIMARY outcome

Timeframe: 28 days

Population: Per-Protocol Population that completed the trial as outlines in SAP.

Baseline-adjusted pre-dose FEV1 measured in the morning following 28 days of treatment. Only the active treatments (test and reference) are compared in this analysis. The placebo arm was used in superiority analysis only.

Outcome measures

Outcome measures
Measure	Test n=432 Participants Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=366 Participants ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Baseline-adjusted Pre-dose FEV1 Measured in the Morning Following 28 Days of Treatment.	0.33 Liters Standard Error 0.02	0.34 Liters Standard Error 0.02	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 hours

Population: mITT Population that completed serial assessments on Day 1 of treatment.

Statistical Superiority of Test and Reference over Placebo Treatment in Baseline-adjusted area under the serial FEV1-time curve

Outcome measures

Outcome measures
Measure	Test n=453 Participants Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=379 Participants ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo n=91 Participants Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Statistical Superiority of Test and Reference Over Placebo Treatment in Baseline-adjusted Area Under the Serial FEV1-time Curve	4.02 liters x hours Standard Error 0.17	3.94 liters x hours Standard Error 0.18	1.21 liters x hours Standard Error 0.35

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Population: mITT Population that completed the study.

Statistical Superiority of Test and Reference over Placebo Treatment in Baseline-adjusted pre-dose FEV1 measured in the morning following 28 days of treatment

Outcome measures

Outcome measures
Measure	Test n=462 Participants Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=395 Participants ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo n=91 Participants Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Statistical Superiority of Test and Reference Over Placebo Treatment in Baseline-adjusted Pre-dose FEV1 Measured in the Morning Following 28 Days of Treatment	0.33 Liters Standard Error 0.02	0.33 Liters Standard Error 0.02	0.11 Liters Standard Error 0.04

Adverse Events

Test

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Reference

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Test n=485 participants at risk Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=413 participants at risk ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo n=101 participants at risk Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Nervous system disorders Ischaemic Stroke	0.00% 0/485 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	0.24% 1/413 • Number of events 1 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	0.00% 0/101 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/485 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	0.24% 1/413 • Number of events 1 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	0.00% 0/101 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.

Other adverse events

Other adverse events
Measure	Test n=485 participants at risk Fluticasone Propionate and Salmeterol Inhalation Powder, 100 mcg/50 mcg Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Reference n=413 participants at risk ADVAIR DISKUS® 100/50 (fluticasone propionate and salmeterol) Inhalation Powder Fluticasone Propionate and Salmeterol Inhalation Powder: 100/50 mcg per actuation Dose: 1 inhalation twice daily	Placebo n=101 participants at risk Placebo Placebo Inhalation Powder: No active content Dose: 1 inhalation twice daily
Respiratory, thoracic and mediastinal disorders Asthma	0.62% 3/485 • Number of events 3 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	0.24% 1/413 • Number of events 1 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.	5.0% 5/101 • Number of events 5 • AEs were collected from each subject from the time of ICF signature until the end of study. Total duration for each subject was approximately 3-4 months. AEs were collected at study visits and via the diaries.

Additional Information

Director, PD/CE Studies

Teva Pharmaceuticals, USA

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right to review and approve all publications based off data from the study.
Publication restrictions are in place

Restriction type: OTHER