Trial Outcomes & Findings for Pharmacogenetics of b2-Agonists in Asthma. (NCT NCT00708227)
NCT ID: NCT00708227
Last Updated: 2018-02-22
Results Overview
Visit 2 log10 PC20 after receiving 2 weeks of Flovent
Recruitment status
COMPLETED
Target enrollment
88 participants
Primary outcome timeframe
Visit 2:12 hours after last dose of Flovent
Results posted on
2018-02-22
Participant Flow
Participants were recruited from Nemours Children's Health System, the University of Florida Jacksonville, health fairs and events, Edward Waters College, and from previous study participation. Participants were recruited between January 2008 and October 2011
Enrolled participants were excluded from receiving planned study treatment if they did not meet the ADRB2 genotype criteria and if they did not have a methacholine PC20 of 12.5mg/ml or less.
Participant milestones
| Measure |
Whites ADRB2:ARG16ARG
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
fluticasone: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
Whites ADRb2:GLY16GLY
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:ARG16ARG
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:GLY16GlY
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
19
|
26
|
18
|
25
|
|
Overall Study
COMPLETED
|
18
|
21
|
17
|
22
|
|
Overall Study
NOT COMPLETED
|
1
|
5
|
1
|
3
|
Reasons for withdrawal
| Measure |
Whites ADRB2:ARG16ARG
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
fluticasone: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
Whites ADRb2:GLY16GLY
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:ARG16ARG
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:GLY16GlY
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
|---|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
3
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
0
|
1
|
Baseline Characteristics
Pharmacogenetics of b2-Agonists in Asthma.
Baseline characteristics by cohort
| Measure |
Whites ADRB2:ARG16ARG
n=19 Participants
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol or 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
fluticasone: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
Whites ADRB2:GLY16GLY
n=26 Participants
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol or 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
Salmeterol: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:ARG16ARG
n=18 Participants
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol or 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
fluticasone: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
African Americans ADRB2:GLY16GLY
n=25 Participants
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol or 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
fluticasone: Fluticasone propionate MDI(dose to be determined by patient's current treatment) for 2 weeks, followed by Advair(R)Diskus (same dose of fluticasone propionate) for 2 weeks; Ipratropium bromide MDI used for prn symptom relief
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
30 Participants
n=31 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
52 Participants
n=31 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
|
Age, Continuous
|
34 years
STANDARD_DEVIATION 19 • n=99 Participants
|
37 years
STANDARD_DEVIATION 20 • n=107 Participants
|
27 years
STANDARD_DEVIATION 21 • n=206 Participants
|
28 years
STANDARD_DEVIATION 17 • n=7 Participants
|
32 years
STANDARD_DEVIATION 19 • n=31 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
61 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
27 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
43 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
45 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
19 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
88 Participants
n=31 Participants
|
|
ADRB2 Genotype at Codon 16
|
19 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
88 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Visit 2:12 hours after last dose of FloventPopulation: All participants who had a methacholine challenge at Visit 2. All participants had received Flovent for 2 weeks.
Visit 2 log10 PC20 after receiving 2 weeks of Flovent
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=25 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=17 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=23 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Log10 PC20 to Methacholine After Visit 2
|
0.54 log10 mg/mL
Standard Deviation 0.65
|
0.48 log10 mg/mL
Standard Deviation 0.71
|
0.16 log10 mg/mL
Standard Deviation 0.57
|
0.53 log10 mg/mL
Standard Deviation 0.67
|
PRIMARY outcome
Timeframe: Visit 3:12 hours after the last dose of AdvairPopulation: All participants who had a methacholine challenge at Visit 3. All participants had received Advair for 2 weeks.
Visit 3 Log10 PC20 after receiving 2 weeks of Advair
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=23 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=17 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=22 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Log10 PC20 to Methacholine After Visit 3
|
0.75 log10 mg/mL
Standard Deviation 0.65
|
0.78 log10 mg/mL
Standard Deviation 0.60
|
0.35 log10 mg/mL
Standard Deviation 0.63
|
0.75 log10 mg/mL
Standard Deviation 0.65
|
PRIMARY outcome
Timeframe: 36 hours after the last dose of AdvairPopulation: All participants who had a methacholine challenge at Visit 4. All participants had discontinued Advair for 36 hours.
Visit 4 log10 PC20 to Methacholine after stopping Advair
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=21 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=17 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=22 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Log10 PC20 to Methacholine After Visit 4
|
0.73 log10 mg/mL
Standard Deviation 0.61
|
0.89 log10 mg/mL
Standard Deviation 0.57
|
0.36 log10 mg/mL
Standard Deviation 0.52
|
0.70 log10 mg/mL
Standard Deviation 0.66
|
SECONDARY outcome
Timeframe: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 12 hours after the last dose of Flovent.Population: All participants who had received Flovent for 2 weeks at Visit 2.
The area under the curve (AUC) bronchodilator response after Visit 2 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had received Flovent for 2 weeks at Visit 2.
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=25 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=25 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Bronchodilator Response to Methacholine (PC20) After Visit 2
|
188.5 Liters*min
Standard Deviation 67.55
|
196.6 Liters*min
Standard Deviation 63.3
|
169.9 Liters*min
Standard Deviation 58.97
|
161.4 Liters*min
Standard Deviation 42.7
|
SECONDARY outcome
Timeframe: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 12 hours after the last dose of AdvairPopulation: The area under the curve (AUC) bronchodilator response after Visit 3 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached. Participants had received Advair for 2 weeks at Visit 3.
The area under the curve (AUC) bronchodilator response after Visit 3 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had received Advair for 2 weeks at Visit 3.
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=23 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=17 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=22 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Bronchodilator Response Following Methacholine Challenge at Visit 3
|
183.6 Liters*min
Standard Deviation 67.02
|
189.2 Liters*min
Standard Deviation 61.08
|
160.0 Liters*min
Standard Deviation 48.01
|
157.7 Liters*min
Standard Deviation 45.28
|
SECONDARY outcome
Timeframe: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 36 hours after the last dose of AdvairPopulation: The area under the curve (AUC) bronchodilator response after Visit 3 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached. Participants had received Advair for 2 weeks at Visit 3.
The area under the curve (AUC) bronchodilator response after Visit 4 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had discontinued Advair for 36 hours.
Outcome measures
| Measure |
Whites ADRB2:ARG16ARG
n=18 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
Whites ADRB2:Gly16Gly
n=21 Participants
Log10 methacholine PC20 data in Whites with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:ARG16ARG
n=17 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 ARG16ARG genotype after receiving 2 weeks of Flovent.
|
African Americans ADRB2:GLY16GLY
n=22 Participants
Log10 methacholine PC20 data in African Americans with the ADRB2 GLY16GLY genotype after receiving 2 weeks of Flovent.
|
|---|---|---|---|---|
|
Bronchodilator Response Following Methacholine Challenge at Visit 4
|
187.3 Liters*min
Standard Deviation 66.17
|
187.1 Liters*min
Standard Deviation 58.31
|
163.2 Liters*min
Standard Deviation 46.70
|
157.7 Liters*min
Standard Deviation 36.44
|
Adverse Events
Whites ADRB2:ARG16ARG
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Whites ADRB2:GLY16GLY
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
African American ADRB2:ARG16ARG
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
African American ADRB2:GLY16GLY
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Whites ADRB2:ARG16ARG
n=19 participants at risk
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
|
Whites ADRB2:GLY16GLY
n=26 participants at risk
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
|
African American ADRB2:ARG16ARG
n=18 participants at risk
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
|
African American ADRB2:GLY16GLY
n=25 participants at risk
All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation
|
0.00%
0/19 • Adverse event data were collected during the study period from Visit 1 through Visit 4 (approximately 4 weeks total follow-up).
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected during the study period from Visit 1 through Visit 4 (approximately 4 weeks total follow-up).
|
0.00%
0/18 • Adverse event data were collected during the study period from Visit 1 through Visit 4 (approximately 4 weeks total follow-up).
|
0.00%
0/25 • Adverse event data were collected during the study period from Visit 1 through Visit 4 (approximately 4 weeks total follow-up).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place