Trial Outcomes & Findings for Bioequivalence Between Albuterol Sulfate Inhalation Aerosol 108 mcg Per Actuation and Proair HFA (Albuterol Sulfate) Inhalation Aerosol 90 mcg Per Actuation in Healthy Volunteers Under Fasting Conditions (NCT NCT04803734)

NCT ID: NCT04803734

Last Updated: 2024-03-18

Results Overview

The maximal observed plasma concentration of Albuterol Sulfate.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

60 participants

Primary outcome timeframe

0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Results posted on

2024-03-18

Participant Flow

Eighty-four subjects were recruited and screened for the eligibility.

Sixty eligible subjects were randomized in the study.

Participant milestones

Participant milestones
Measure
Albuterol Sulfate Inhalation Aerosol First, Then ProairHFA (Albuterol Sulfate) Inhalation Aerosol
Subjects who were randomized to the sequence of Albuterol Sulfate Inhalation Aerosol first, then ProairHFA (albuterol sulfate) Inhalation Aerosol received an orally inhaled dose of 2 puffs of the test product (Albuterol Sulfate inhalation aerosol 108mcg per actuation) in First Intervention Period 1. After the Washout (14 days) period, subjects received an orally inhaled dose of 2 puffs of the reference product (Proair HFA \[albuterol sulfate\] Inhalation Aerosol 90 mcg per actuation) in the Second Intervention Period 2.
Proair HFA (Albuterol Sulfate) Inhalation Aerosol First, Then Albuterol Sulfate Inhalation Aerosol
Subjects who were randomized to the sequence of Proair HFA (albuterol sulfate) Inhalation Aerosol first, then Albuterol Sulfate Inhalation Aerosol received an orally inhaled dose of 2 puffs of the reference product (Proair HFA \[albuterol sulfate\] Inhalation Aerosol 90 mcg per actuation) in First Intervention Period 1. After the Washout (14 days) period, subjects received an orally inhaled dose of 2 puffs of the test product (Albuterol Sulfate inhalation aerosol 108mcg per actuation) in the Second Intervention Period 2.
Overall Study
STARTED
30
30
Overall Study
COMPLETED
30
28
Overall Study
NOT COMPLETED
0
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Albuterol Sulfate Inhalation Aerosol First, Then ProairHFA (Albuterol Sulfate) Inhalation Aerosol
Subjects who were randomized to the sequence of Albuterol Sulfate Inhalation Aerosol first, then ProairHFA (albuterol sulfate) Inhalation Aerosol received an orally inhaled dose of 2 puffs of the test product (Albuterol Sulfate inhalation aerosol 108mcg per actuation) in First Intervention Period 1. After the Washout (14 days) period, subjects received an orally inhaled dose of 2 puffs of the reference product (Proair HFA \[albuterol sulfate\] Inhalation Aerosol 90 mcg per actuation) in the Second Intervention Period 2.
Proair HFA (Albuterol Sulfate) Inhalation Aerosol First, Then Albuterol Sulfate Inhalation Aerosol
Subjects who were randomized to the sequence of Proair HFA (albuterol sulfate) Inhalation Aerosol first, then Albuterol Sulfate Inhalation Aerosol received an orally inhaled dose of 2 puffs of the reference product (Proair HFA \[albuterol sulfate\] Inhalation Aerosol 90 mcg per actuation) in First Intervention Period 1. After the Washout (14 days) period, subjects received an orally inhaled dose of 2 puffs of the test product (Albuterol Sulfate inhalation aerosol 108mcg per actuation) in the Second Intervention Period 2.
Overall Study
Withdrawal by Subject
0
1
Overall Study
Protocol Violation
0
1

Baseline Characteristics

Bioequivalence Between Albuterol Sulfate Inhalation Aerosol 108 mcg Per Actuation and Proair HFA (Albuterol Sulfate) Inhalation Aerosol 90 mcg Per Actuation in Healthy Volunteers Under Fasting Conditions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=60 Participants
Summary of Demographic Data and Baseline Characteristics for All Study Participants.
Age, Continuous
31.9 years
STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male
Female
19 Participants
n=5 Participants
Sex: Female, Male
Male
41 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
60 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Height
167.8 cm
STANDARD_DEVIATION 6.8 • n=5 Participants
Weight
65.5 kg
STANDARD_DEVIATION 8.6 • n=5 Participants
Body mass index (BMI)
23.2 kg/m^2
STANDARD_DEVIATION 2.2 • n=5 Participants

PRIMARY outcome

Timeframe: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

The maximal observed plasma concentration of Albuterol Sulfate.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
Cmax
812.477 pg/mL
Standard Deviation 281.148
945.456 pg/mL
Standard Deviation 359.695

PRIMARY outcome

Timeframe: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Area under the concentration time curve from time zero until the last measurable concentration or last sampling time t, whichever occurs first.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
AUC(0-t)
4806.319 hr*pg/mL
Standard Deviation 981.477
5090.449 hr*pg/mL
Standard Deviation 1053.602

PRIMARY outcome

Timeframe: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Area under the concentration time curve from time zero to infinity.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
AUC(0-inf)
5204.806 hr*pg/mL
Standard Deviation 1081.862
5509.006 hr*pg/mL
Standard Deviation 1148.747

SECONDARY outcome

Timeframe: 0-24 hours

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Time when the maximal plasma concentration is observed.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
Tmax
0.929 hr
Standard Deviation 1.089
0.514 hr
Standard Deviation 0.529

SECONDARY outcome

Timeframe: 0-24 hours

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Terminal elimination half-life, estimated as ln(2)/λ.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
T1/2
6.928 hr
Standard Deviation 1.165
6.985 hr
Standard Deviation 1.357

SECONDARY outcome

Timeframe: 0-24 hours

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Terminal elimination rate constant, estimated by linear regression analysis of the terminal portion of the ln-concentration vs. time plot.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
Kel(λ)
0.103 1/hr
Standard Deviation 0.019
0.103 1/hr
Standard Deviation 0.021

SECONDARY outcome

Timeframe: 0-24 hours

Population: R014, R040, R055, R058 had protocol issues including significantly delayed blood sampling and leakage of drug during dosing. R029 and R058 had pre-dose concentrations \> 5% of Cmax. Data of remaining 53 subjects was considered for pharmacokinetic and statistical analysis.

Mean residence time (MRT) is calculated by the area under the first moment curve dividing by area under the concentration time curve.

Outcome measures

Outcome measures
Measure
Albuterol Sulfate Inhalation Aerosol
n=53 Participants
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Proair HFA (Albuterol Sulfate) Inhalation Aerosol
n=53 Participants
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
Mean Residence Time (MRT)
8.629 hr
Standard Deviation 1.202
8.474 hr
Standard Deviation 1.455

Adverse Events

Test Group

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Reference Group

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Test Group
n=60 participants at risk
Albuterol Sulfate inhalation aerosol 108 mcg per actuation: MDI, 2 puffs, single dose, fasting
Reference Group
n=58 participants at risk
Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation: MDI, 2 puffs, single dose, fasting
Infections and infestations
Throat infection
1.7%
1/60 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
0.00%
0/58 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
Investigations
Aspartate aminotransferase (AST) increased
1.7%
1/60 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
0.00%
0/58 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
Investigations
Creatinine increased
1.7%
1/60 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
0.00%
0/58 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
Investigations
Alanine aminotransferase (ALT) increased
1.7%
1/60 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
0.00%
0/58 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
Metabolism and nutrition disorders
Hypertriglyceridemia
0.00%
0/60 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.
1.7%
1/58 • Approximately 16 days for each subject.
The population for safety evaluation was defined as all subjects who took at least one of study drugs. Only AE occurs after first dosing will be analyzed for safety assessment.

Additional Information

Sabina Chien

Intech Biopharm Ltd.

Phone: +886-2-7721-8877

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place