Trial Outcomes & Findings for Evaluation of the Pharmacokinetics and the Pharmacodynamics of Different Dry Powder Inhalation Formulations of AZD3199 in Patients With Asthma (NCT NCT01348139)
NCT ID: NCT01348139
Last Updated: 2013-03-05
Results Overview
Peak effect (Emax) within 0-24 hours of FEV1, for treatment visits 2 to 7.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
0-24 hrs
Results posted on
2013-03-05
Participant Flow
A total of 39 patients were enrolled at 3 centres in Sweden. Of these, 26 patients were randomised to receive a treatment sequence consisting of 6 different treatments in random order. The number of patients randomised was well balanced across all the treatment periods. In total, 25 patients completed the study.
Participant milestones
| Measure |
1400 μg / Placebo / 880 μg / 1200 μg / 800 μg / 300 μg
AZD3199 1400 μg SID followed by Placebo followed by AZD3199 880 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 800 μg SID followed by AZD3199 300 μg Turbuhaler inhaler.
|
880 μg / 1400 μg / 800 μg / Placebo / 300 μg / 1200 μg
AZD3199 880 μg SID followed by AZD3199 1400 μg SID followed by AZD3199 800 μg SID followed by Placebo followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 1200 μg Turbuhaler inhaler.
|
800 μg / 880 μg / 300 μg / 1400 μg / 1200 μg / Placebo
AZD3199 800 μg SID followed by AZD3199 880 μg SID followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 1400 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by Placebo.
|
300 μg / 800 μg / 1200 μg / 880 μg / Placebo / 1400 μg
AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 800 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 880 μg SID followed by Placebo followed by AZD3199 1400 μg SID.
|
1200 μg / 300 μg / Placebo / 800 μg / 1400 μg / 880 μg
AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 300 μg Turbuhaler inhaler followed by Placebo followed by AZD3199 800 μg SID followed by AZD3199 1400 μg SID followed by AZD3199 880 μg SID.
|
Placebo / 1200 μg / 1400 μg / 300 μg / 880 μg / 800 μg
Placebo followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 1400 μg SID followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 880 μg SID followed by AZD3199 800 μg SID.
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
5
|
4
|
4
|
4
|
5
|
4
|
|
Period 1
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 1
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 2
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 3
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 4
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 5
STARTED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 5
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 6
STARTED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 6
COMPLETED
|
4
|
4
|
4
|
4
|
5
|
4
|
|
Period 6
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
1400 μg / Placebo / 880 μg / 1200 μg / 800 μg / 300 μg
AZD3199 1400 μg SID followed by Placebo followed by AZD3199 880 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 800 μg SID followed by AZD3199 300 μg Turbuhaler inhaler.
|
880 μg / 1400 μg / 800 μg / Placebo / 300 μg / 1200 μg
AZD3199 880 μg SID followed by AZD3199 1400 μg SID followed by AZD3199 800 μg SID followed by Placebo followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 1200 μg Turbuhaler inhaler.
|
800 μg / 880 μg / 300 μg / 1400 μg / 1200 μg / Placebo
AZD3199 800 μg SID followed by AZD3199 880 μg SID followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 1400 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by Placebo.
|
300 μg / 800 μg / 1200 μg / 880 μg / Placebo / 1400 μg
AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 800 μg SID followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 880 μg SID followed by Placebo followed by AZD3199 1400 μg SID.
|
1200 μg / 300 μg / Placebo / 800 μg / 1400 μg / 880 μg
AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 300 μg Turbuhaler inhaler followed by Placebo followed by AZD3199 800 μg SID followed by AZD3199 1400 μg SID followed by AZD3199 880 μg SID.
|
Placebo / 1200 μg / 1400 μg / 300 μg / 880 μg / 800 μg
Placebo followed by AZD3199 1200 μg Turbuhaler inhaler followed by AZD3199 1400 μg SID followed by AZD3199 300 μg Turbuhaler inhaler followed by AZD3199 880 μg SID followed by AZD3199 800 μg SID.
|
|---|---|---|---|---|---|---|
|
Period 1
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Evaluation of the Pharmacokinetics and the Pharmacodynamics of Different Dry Powder Inhalation Formulations of AZD3199 in Patients With Asthma
Baseline characteristics by cohort
| Measure |
Baseline Total
n=26 Participants
Total number of patients randomised and treated in the study.
|
|---|---|
|
Age Continuous
All
|
36.5 Years
STANDARD_DEVIATION 11.29 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
24 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0-24 hrsPeak effect (Emax) within 0-24 hours of FEV1, for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=25 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
Emax: Maximum Value of FEV1 for Every Treatment Visits
|
3.788 Liters
Standard Deviation 0.782
|
3.784 Liters
Standard Deviation 0.724
|
3.756 Liters
Standard Deviation 0.733
|
3.763 Liters
Standard Deviation 0.744
|
3.847 Liters
Standard Deviation 0.781
|
3.498 Liters
Standard Deviation 0.676
|
PRIMARY outcome
Timeframe: 22-26 hrs.Population: PD analysis set
Trough effect (E22-26h) will be computed from the repeated measurements collected after each single dose during 22-26 hours of FEV1 from visit 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=25 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
E22-26h: The Average of the FEV1 Values Between 22 and 26 h for Every Treatment Visit
|
3.448 Liters
Standard Deviation 0.709
|
3.453 Liters
Standard Deviation 0.739
|
3.495 Liters
Standard Deviation 0.730
|
3.448 Liters
Standard Deviation 0.732
|
3.569 Liters
Standard Deviation 0.761
|
3.310 Liters
Standard Deviation 0.723
|
SECONDARY outcome
Timeframe: 0 - 24 hrs.Population: PD analysis set
Time to peak effect (tEmax), within 0-24 hours of FEV1, for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=25 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
tEmax: Time to Maximum Value of FEV1 for Every Treatment Visit
|
2.000 Hours
Interval 0.5 to 10.0
|
2.000 Hours
Interval 0.5 to 22.0
|
2.000 Hours
Interval 0.25 to 24.0
|
1.000 Hours
Interval 0.25 to 22.0
|
4.000 Hours
Interval 0.25 to 24.0
|
10.000 Hours
Interval 0.0 to 24.0
|
SECONDARY outcome
Timeframe: FEV1 at 5 minPopulation: PD analysis set
Onset of effect (E5min), observed at 5 min. FEV1 for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=25 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
E5min: The Value of FEV1 at 5 Min for Every Treatment Visit.
|
3.406 Liters
Standard Deviation 0.743
|
3.449 Liters
Standard Deviation 0.663
|
3.496 Liters
Standard Deviation 0.692
|
3.489 Liters
Standard Deviation 0.653
|
3.486 Liters
Standard Deviation 0.723
|
3.188 Liters
Standard Deviation 0.586
|
SECONDARY outcome
Timeframe: 0 - 24 hrsPopulation: PD analysis set
Average effect over 0-24 hours of FEV1 (E0-24h), for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=25 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
E0-24h: The Average of the FEV1 Values Between 0 and 24 h for Every Treatment Visit
|
3.489 Liters
Standard Deviation 0.710
|
3.526 Liters
Standard Deviation 0.737
|
3.537 Liters
Standard Deviation 0.729
|
3.493 Liters
Standard Deviation 0.707
|
3.636 Liters
Standard Deviation 0.776
|
3.287 Liters
Standard Deviation 0.671
|
SECONDARY outcome
Timeframe: 0 - 4 hrs.Population: PD analysis set
Peak effect (Emax) within 0-4 hours of pulse, for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=26 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
Emax: Maximum Value of Pulse for Every Treatment Visits
|
66.15 Beats/min
Standard Deviation 11.10
|
64.36 Beats/min
Standard Deviation 10.10
|
64.24 Beats/min
Standard Deviation 9.27
|
64.84 Beats/min
Standard Deviation 10.18
|
66.20 Beats/min
Standard Deviation 12.38
|
64.12 Beats/min
Standard Deviation 11.22
|
SECONDARY outcome
Timeframe: 0 - 4 hrs.Population: PD analysis set
Average effect (E0-4h) of Pulse, for treatment visits 2 to 7.
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=26 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
n=25 Participants
Placebo
|
|---|---|---|---|---|---|---|
|
E0-4h: The Average of the Pulse Values Between 0 and 4 h for Every Treatment Visit
|
59.85 Beats/min
Standard Deviation 9.13
|
59.13 Beats/min
Standard Deviation 8.83
|
59.07 Beats/min
Standard Deviation 8.38
|
58.77 Beats/min
Standard Deviation 8.66
|
59.73 Beats/min
Standard Deviation 9.63
|
58.66 Beats/min
Standard Deviation 10.40
|
SECONDARY outcome
Timeframe: 0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.Population: PK analysis set
Maximum plasma concentration (Cmax) for AZD3199 doses
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=26 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
Placebo
|
|---|---|---|---|---|---|---|
|
Cmax: Maximum Plasma Concentration
|
6.93846 nmol/L
Standard Deviation 2.497151
|
5.81240 nmol/L
Standard Deviation 2.497151
|
6.29560 nmol/L
Standard Deviation 2.827910
|
3.01836 nmol/L
Standard Deviation 1.294151
|
13.54120 nmol/L
Standard Deviation 4.337208
|
—
|
SECONDARY outcome
Timeframe: 0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.Population: PK analysis set
Area under the plasma concentration-time curve from zero to infinity (AUC), for AZD3199 doses
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=26 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
Placebo
|
|---|---|---|---|---|---|---|
|
AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC),
|
21.83501 nmol*h/L
Standard Deviation 10.43729
|
20.21716 nmol*h/L
Standard Deviation 10.19966
|
22.80110 nmol*h/L
Standard Deviation 11.71379
|
10.25880 nmol*h/L
Standard Deviation 4.886541
|
37.48982 nmol*h/L
Standard Deviation 13.11484
|
—
|
SECONDARY outcome
Timeframe: 0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.Population: PK analysis set
Time to maximum plasma concentration (tmax), for AZD3199 doses
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=26 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=25 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=25 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=25 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=25 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
Placebo
|
|---|---|---|---|---|---|---|
|
Tmax:Time to Maximum Plasma Concentration
|
0.47000 Hours
Interval 0.23 to 0.62
|
0.48000 Hours
Interval 0.27 to 0.62
|
0.52000 Hours
Interval 0.28 to 1.03
|
0.52000 Hours
Interval 0.25 to 0.58
|
0.48000 Hours
Interval 0.27 to 0.58
|
—
|
SECONDARY outcome
Timeframe: 0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.Population: PK analysis set
Terminal half-life (t1/2),for AZD3199 doses
Outcome measures
| Measure |
Arm 1 - AZD3199 1400 μg
n=9 Participants
AZD3199 1400 μg SID
|
Arm 2 - AZD3199 880 μg
n=8 Participants
AZD3199 880 μg SID
|
Arm 3 - AZD3199 800 μg
n=8 Participants
AZD3199 800 μg SID
|
Arm 4 - AZD3199 300 μg
n=8 Participants
AZD3199 300 μg Turbuhaler inhaler
|
Arm 5 - AZD3199 1200 μg
n=9 Participants
AZD3199 1200 μg Turbuhaler inhaler
|
Arm 6 - Placebo
Placebo
|
|---|---|---|---|---|---|---|
|
t1/2 :Terminal Half-life
|
80.97301 Hours
Standard Deviation 24.65131
|
79.24210 Hours
Standard Deviation 22.07879
|
103.7279 Hours
Standard Deviation 113.8432
|
77.46496 Hours
Standard Deviation 47.17895
|
88.99700 Hours
Standard Deviation 46.23237
|
—
|
Adverse Events
AZD3199 1400 μg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
AZD3199 880 μg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
AZD3199 800 μg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
AZD3199 300 μg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
AZD3199 1200 μg
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZD3199 1400 μg
n=26 participants at risk
AZD3199 1400 μg SID
|
AZD3199 880 μg
n=25 participants at risk
AZD3199 880 μg SID
|
AZD3199 800 μg
n=25 participants at risk
AZD3199 800 μg SID
|
AZD3199 300 μg
n=25 participants at risk
AZD3199 300 μg Turbuhaler inhaler
|
AZD3199 1200 μg
n=25 participants at risk
AZD3199 1200 μg Turbuhaler inhaler
|
Placebo
n=25 participants at risk
Placebo
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/26
|
8.0%
2/25
|
0.00%
0/25
|
0.00%
0/25
|
0.00%
0/25
|
0.00%
0/25
|
|
Infections and infestations
NASOPHARYNGITIS
|
19.2%
5/26
|
0.00%
0/25
|
12.0%
3/25
|
12.0%
3/25
|
20.0%
5/25
|
16.0%
4/25
|
|
Nervous system disorders
DYSGEUSIA
|
15.4%
4/26
|
20.0%
5/25
|
24.0%
6/25
|
16.0%
4/25
|
24.0%
6/25
|
0.00%
0/25
|
|
Nervous system disorders
HEADACHE
|
7.7%
2/26
|
12.0%
3/25
|
8.0%
2/25
|
0.00%
0/25
|
16.0%
4/25
|
8.0%
2/25
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/26
|
0.00%
0/25
|
4.0%
1/25
|
4.0%
1/25
|
8.0%
2/25
|
0.00%
0/25
|
|
Respiratory, thoracic and mediastinal disorders
THROAT IRRITATION
|
0.00%
0/26
|
4.0%
1/25
|
0.00%
0/25
|
0.00%
0/25
|
8.0%
2/25
|
0.00%
0/25
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60