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Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00736489
Collaborator
(none)
37
Enrollment
4
Locations
6
Arms
4
Duration (Months)
9.3
Patients Per Site
2.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the pharmacodynamics of single doses of AZD3199 in asthmatic patients.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
37 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II, Double-blind, Placebo-controlled, Randomised, 6-way Cross-over, Single-dose Study to Investigate the Local and Systemic Effects of 3 Doses of Inhaled AZD3199 (a β2-agonist) Compared to Formoterol in Asthmatic Patients
Study Start Date :
Aug 1, 2008
Actual Primary Completion Date :
Dec 1, 2008
Actual Study Completion Date :
Dec 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: crossover dose 1

AZD3199 120 microgram

Drug: AZD3199
Dry powder for inhalation, single dose
Experimental: crossover dose 2

AZD3199 480 microgram

Drug: AZD3199
Dry powder for inhalation, single dose
Experimental: crossover dose 3

AZD3199 1920 microgram

Drug: AZD3199
Dry powder for inhalation, single dose
Placebo Comparator: crossover dose 4

Placebo

Drug: Placebo
Dry powder for inhalation, single dose
Active Comparator: crossover dose 5

Formoterol 9 microgram

Drug: Formoterol
Dry powder for inhalation, single dose
Other Names:
  • Oxis

    		•
    Active Comparator: crossover dose 6

    Formoterol 36 microgram

    Drug: Formoterol
    Dry powder for inhalation, single dose
    Other Names:
  • Oxis

    		•

    Outcome Measures

    Primary Outcome Measures

    1. FEV1 Peak Effect Within 0 - 24 h Post-dose [0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h]

      Maximum FEV1 value

    2. E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. [22- 26 h post dose]

      Residual FEV1 24 h post-dose

    3. S-potassium, Peak Effect Over 0 - 4 h Post-dose [0, 15min, 30min,1h, 2h, 4h]

      Minimum S-potassium concentration (A well-known effect of beta2-agonists (AZD3199 is a beta2-agonist) is a reduction in serum potassium levels. The minimum value has therefore been evaluated.

    4. S-potassium, Average Effect Over 0 - 4 h Post-dose [0, 15min, 30min,1h, 2h, 4h]

      Average S-potassium concentration

    Secondary Outcome Measures

    1. FEV1 Effect at 5 Min Post-dose [5min]

      FEV1 at 5 minutes

    2. FEV1 Average Effect Over 0 - 24 h Post-dose [0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h]

      FEV1 average effect over 24 h dosing interval

    3. FEV1 Average Effect Over 0 - 12 h Post-dose [0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h]

      FEV1 average effect over 12 h day-time period

    4. FEV1 Average Effect Over 12 - 24 h Post-dose [12h, 14h, 18h, 22h, 24h]

      FEV1 average effect over 12 h night-time period

    5. Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Maximum SBP value over 4 h

    6. Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Average SBP value over 4 h

    7. Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Minimum DBP value over 4 h

    8. Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Average DBP value over 4 h

    9. Pulse, Peak Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Maximum pulse over 4 h

    10. Pulse, Average Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Average pulse over 4 h

    11. Heart Rate, Peak Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Maximum heart rate over 4 h

    12. Heart Rate, Average Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Average heart rate over 4 h

    13. QTcB, Peak Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Maximum QTc Bazett over 4 h

    14. QTcB, Average Effect Over 0 - 4 h Post-dose [0, 30min, 2h, 4h]

      Average QTc Bazett over 4 h

    15. Tremor, Peak Effect Over 0 - 4 h Post-dose [0, 15min, 30min, 1h, 2h, 4h]

      Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

    16. Tremor, Average Effect Over 0 - 4 h Post-dose [0, 15min, 30min, 1h, 2h, 4h]

      Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

    17. Palpitations, Peak Effect Over 0 - 4 h Post-dose [0, 15min, 30min, 1h, 2h, 4h]

      Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

    18. Palpitations, Average Effect Over 0 - 4 h Post-dose [0, 15min, 30min, 1h, 2h, 4h]

      Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

    19. Plasma AZD3199 Cmax [0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h]

      Maximum plasma concentration of AZD3199 measured

    20. Plasma AZD3199 AUC0-24 [0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h]

      Area under the plasma concentration curve from time 0 to 24 h post-dose

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Asthmatic patients with pre-bronchodilatory FEV1 above 60% of predicted normal and above 1.5 liters.

    • Men and post-menopausal women above 18 years of age.

    • Reversible airway obstruction in response to classical beta2-agonist (salbutamol)

    • Non/ex-smokers

    Exclusion Criteria:

    • Any clinically significant disease or disorder other than asthma

    • Any clinically relevant abnormal findings at screening examinations

    • Treatment with systemic glucocorticosteroids within the past 30 days

    • Inhaled corticosteroid use if dosing is not kept constant

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Hvidovre Denmark
    2 Research Site Gothenburg Sweden
    3 Research Site Lulea Sweden
    4 Research Site Lund Sweden

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Prof Leif Bjermer, MD, PhD, University Hospital in Lund, Sweden

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00736489
    Other Study ID Numbers:
    • D0570C00007
    • ToBe
    First Posted:
    Aug 18, 2008
    Last Update Posted:
    May 19, 2014
    Last Verified:
    Apr 1, 2014
    Keywords provided by AstraZeneca
    Asthma
    airway obstruction
    beta2-agonist
    efficacy
    inhalation
    Additional relevant MeSH terms:
    Airway Obstruction
    Formoterol Fumarate
    AZD-3199

    Study Results

    Participant Flow

    Recruitment Details The study has been performed in Sweden and Denmark at two University hospital clinics and two CROs. The recruitment period was between 11 August 2008 to 22 October 2008.
    Pre-assignment Detail
    Arm/Group Title APCDEBa BADEPCa CBEPADa DCPABEa EDABCPa PEBCDAa
    Arm/Group Description AZD3199 120 Mcg followed by Placebo followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg. AZD3199 480 Mcg followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 1920 Mcg. AZD3199 1920 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg . Formoterol 9 Mcg followed by AZD3199 1920 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg. Formoterol 36 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Placebo. Placebo followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg.
    Period Title: Period 1
    STARTED 6 5 6 7 7 6
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 1 0 0 0 0 1
    Period Title: Period 1
    STARTED 5 5 6 7 7 5
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: Period 1
    STARTED 5 5 6 7 7 5
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: Period 1
    STARTED 5 5 6 7 7 5
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: Period 1
    STARTED 5 5 6 7 7 5
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: Period 1
    STARTED 5 5 6 7 7 5
    COMPLETED 5 5 6 7 7 5
    NOT COMPLETED 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Baseline Total
    Arm/Group Description Total number of patients randomized and treated in the study
    Overall Participants 37
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    40.3
    Sex: Female, Male (Count of Participants)
    Female
    5
    13.5%
    Male
    32
    86.5%

    Outcome Measures

    1. Primary Outcome
    Title FEV1 Peak Effect Within 0 - 24 h Post-dose
    Description Maximum FEV1 value
    Time Frame 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 34
    Mean (Standard Deviation) [L]
    3.56
    (0.94)
    3.62
    (0.94)
    3.70
    (1.02)
    3.62
    (1.01)
    3.69
    (0.97)
    3.44
    (0.99)
    2. Primary Outcome
    Title E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit.
    Description Residual FEV1 24 h post-dose
    Time Frame 22- 26 h post dose

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 34
    Mean (Standard Deviation) [L]
    3.31
    (0.96)
    3.35
    (0.93)
    3.40
    (0.94)
    3.26
    (0.94)
    3.36
    (0.97)
    3.23
    (0.96)
    3. Primary Outcome
    Title S-potassium, Peak Effect Over 0 - 4 h Post-dose
    Description Minimum S-potassium concentration (A well-known effect of beta2-agonists (AZD3199 is a beta2-agonist) is a reduction in serum potassium levels. The minimum value has therefore been evaluated.
    Time Frame 0, 15min, 30min,1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on AZD3199 1920 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 33 35 35 35
    Mean (Standard Deviation) [mmol/L]
    4.04
    (0.19)
    4.03
    (0.25)
    3.98
    (0.28)
    4.04
    (0.20)
    3.84
    (0.21)
    4.04
    (0.23)
    4. Primary Outcome
    Title S-potassium, Average Effect Over 0 - 4 h Post-dose
    Description Average S-potassium concentration
    Time Frame 0, 15min, 30min,1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on AZD3199 1920 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 33 35 35 35
    Mean (Standard Deviation) [mmol/L]
    4.22
    (0.19)
    4.21
    (0.26)
    4.17
    (0.26)
    4.19
    (0.20)
    3.99
    (0.17)
    4.21
    (0.25)
    5. Secondary Outcome
    Title FEV1 Effect at 5 Min Post-dose
    Description FEV1 at 5 minutes
    Time Frame 5min

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on Placebo and 1 on AZD3199 480 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 34 35 35 35 33
    Mean (Standard Deviation) [L]
    3.36
    (0.88)
    3.38
    (0.92)
    3.33
    (1.03)
    3.37
    (0.95)
    3.47
    (0.93)
    3.13
    (0.86)
    6. Secondary Outcome
    Title FEV1 Average Effect Over 0 - 24 h Post-dose
    Description FEV1 average effect over 24 h dosing interval
    Time Frame 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 34
    Mean (Standard Deviation) [L]
    3.31
    (0.93)
    3.36
    (0.91)
    3.44
    (0.95)
    3.35
    (0.98)
    3.46
    (0.96)
    3.19
    (0.95)
    7. Secondary Outcome
    Title FEV1 Average Effect Over 0 - 12 h Post-dose
    Description FEV1 average effect over 12 h day-time period
    Time Frame 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 34
    Mean (Standard Deviation) [L]
    3.33
    (0.92)
    3.40
    (0.89)
    3.48
    (0.97)
    3.40
    (0.98)
    3.51
    (0.95)
    3.20
    (0.96)
    8. Secondary Outcome
    Title FEV1 Average Effect Over 12 - 24 h Post-dose
    Description FEV1 average effect over 12 h night-time period
    Time Frame 12h, 14h, 18h, 22h, 24h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 34
    Mean (Standard Deviation) [L]
    3.28
    (0.95)
    3.33
    (0.92)
    3.41
    (0.94)
    3.30
    (0.98)
    3.40
    (0.98)
    3.19
    (0.95)
    9. Secondary Outcome
    Title Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum SBP value over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [mmHg]
    126.8
    (14.5)
    128.3
    (13.4)
    127.4
    (12.0)
    127.3
    (13.2)
    129.9
    (12.1)
    126.4
    (14.4)
    10. Secondary Outcome
    Title Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose
    Description Average SBP value over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [mmHg]
    121.1
    (13.7)
    121.8
    (11.8)
    121.3
    (11.9)
    120.9
    (12.8)
    122.6
    (11.8)
    121.3
    (13.5)
    11. Secondary Outcome
    Title Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose
    Description Minimum DBP value over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [mmHg]
    67.3
    (10.3)
    67.6
    (7.9)
    66.7
    (9.6)
    66.9
    (9.1)
    66.7
    (9.6)
    68.8
    (8.0)
    12. Secondary Outcome
    Title Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose
    Description Average DBP value over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [mmHg]
    71.4
    (10.0)
    72.0
    (8.9)
    71.6
    (9.5)
    71.5
    (9.2)
    71.0
    (8.6)
    72.7
    (8.4)
    13. Secondary Outcome
    Title Pulse, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum pulse over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [bpm]
    62.1
    (9.4)
    65.0
    (11.0)
    66.7
    (9.9)
    63.6
    (11.0)
    67.3
    (11.6)
    65.3
    (10.4)
    14. Secondary Outcome
    Title Pulse, Average Effect Over 0 - 4 h Post-dose
    Description Average pulse over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [bpm]
    57.1
    (8.0)
    59.0
    (8.7)
    61.9
    (9.1)
    58.6
    (9.4)
    62.8
    (10.1)
    58.8
    (8.8)
    15. Secondary Outcome
    Title Heart Rate, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum heart rate over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [bpm]
    64.0
    (8.8)
    64.1
    (9.6)
    66.9
    (9.5)
    63.8
    (10.2)
    66.8
    (10.9)
    64.5
    (11.3)
    16. Secondary Outcome
    Title Heart Rate, Average Effect Over 0 - 4 h Post-dose
    Description Average heart rate over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [bpm]
    58.3
    (7.9)
    59.0
    (8.5)
    61.8
    (9.0)
    58.6
    (9.2)
    62.7
    (10.0)
    58.1
    (8.6)
    17. Secondary Outcome
    Title QTcB, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum QTc Bazett over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [ms]
    412
    (21.6)
    407
    (22.8)
    413
    (22.0)
    408
    (21.6)
    415
    (24.6)
    408
    (20.8)
    18. Secondary Outcome
    Title QTcB, Average Effect Over 0 - 4 h Post-dose
    Description Average QTc Bazett over 4 h
    Time Frame 0, 30min, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 35 35 35
    Mean (Standard Deviation) [ms]
    398
    (19.9)
    397
    (22.3)
    402
    (21.2)
    395
    (21.4)
    406
    (24.4)
    395
    (19.8)
    19. Secondary Outcome
    Title Tremor, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.
    Time Frame 0, 15min, 30min, 1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 34 35 35 34 34
    Mean (Standard Deviation) [Score on a scale]
    0.06
    (0.24)
    0.06
    (0.24)
    0.17
    (0.45)
    0.11
    (0.32)
    0.47
    (0.66)
    0.03
    (0.17)
    20. Secondary Outcome
    Title Tremor, Average Effect Over 0 - 4 h Post-dose
    Description Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.
    Time Frame 0, 15min, 30min, 1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 34 35 35 34 34
    Mean (Standard Deviation) [Score on a scale]
    0.00
    (0.02)
    0.02
    (0.08)
    0.04
    (0.11)
    0.05
    (0.18)
    0.16
    (0.34)
    0.01
    (0.06)
    21. Secondary Outcome
    Title Palpitations, Peak Effect Over 0 - 4 h Post-dose
    Description Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h
    Time Frame 0, 15min, 30min, 1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 34 35 35 34 34
    Mean (Standard Deviation) [Score on a scale]
    0.03
    (0.17)
    0.03
    (0.17)
    0.09
    (0.37)
    0.00
    (0.00)
    0.18
    (0.52)
    0.00
    (0.00)
    22. Secondary Outcome
    Title Palpitations, Average Effect Over 0 - 4 h Post-dose
    Description Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h
    Time Frame 0, 15min, 30min, 1h, 2h, 4h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 34 35 35 34 34
    Mean (Standard Deviation) [Score on a scale]
    0.00
    (0.02)
    0.01
    (0.05)
    0.02
    (0.08)
    0.00
    (0.00)
    0.11
    (0.33)
    0.00
    (0.00)
    23. Secondary Outcome
    Title Plasma AZD3199 Cmax
    Description Maximum plasma concentration of AZD3199 measured
    Time Frame 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacokinetic analysis set.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 0 0 0
    Geometric Mean (Full Range) [nmol/L]
    0.99
    5.39
    24.55
    24. Secondary Outcome
    Title Plasma AZD3199 AUC0-24
    Description Area under the plasma concentration curve from time 0 to 24 h post-dose
    Time Frame 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h

    Outcome Measure Data

    Analysis Population Description
    Two patients discontinued after the first treatment period and were excluded from pharmacokinetic analysis set.
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    Measure Participants 35 35 35 0 0 0
    Geometric Mean (Full Range) [nmol*h/L]
    1.83
    9.75
    46.06

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Arm/Group Description AZD3199 120 Mcg inhaled via Turbuhaler AZD3199 480 Mcg inhaled via Turbuhaler AZD3199 1920 Mcg inhaled via Turbuhaler Formoterol 9 Mcg inhaled via Turbuhaler Formoterol 36 Mcg inhaled via Turbuhaler Placebo inhaled via Turbuhaler
    All Cause Mortality
    AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/36 (0%) 0/35 (0%) 0/35 (0%) 0/35 (0%) 0/35 (0%) 0/36 (0%)
    Other (Not Including Serious) Adverse Events
    AZD3199 120 mcg AZD3199 480 mcg AZD3199 1920 mcg Formoterol 9 mcg Formoterol 36 mcg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/36 (11.1%) 3/35 (8.6%) 10/35 (28.6%) 2/35 (5.7%) 4/35 (11.4%) 6/36 (16.7%)
    Infections and infestations
    Nasopharyngitis 3/36 (8.3%) 1/35 (2.9%) 4/35 (11.4%) 0/35 (0%) 1/35 (2.9%) 4/36 (11.1%)
    Nervous system disorders
    Headache 1/36 (2.8%) 3/35 (8.6%) 4/35 (11.4%) 2/35 (5.7%) 3/35 (8.6%) 2/36 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Throat irritation 0/36 (0%) 0/35 (0%) 4/35 (11.4%) 0/35 (0%) 0/35 (0%) 0/36 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Prior to any publication or disclosure, the PI provides AstraZeneca with preliminary data and drafts and with the proposed final manuscript. AstraZeneca shall have a period of 30 days from receipt of the proposed final manuscript to review it and may within such time frame require that submission for publication or disclosure be delayed.

    Results Point of Contact

    Name/Title Carin Jorup, MSD
    Organization AstraZeneca
    Phone
    Email ClinicalTrialTransparency@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00736489
    Other Study ID Numbers:
    • D0570C00007
    • ToBe
    First Posted:
    Aug 18, 2008
    Last Update Posted:
    May 19, 2014
    Last Verified:
    Apr 1, 2014