Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00736489
First received: August 15, 2008
Last updated: May 8, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Asthma
Airway Obstruction
Drug: AZD3199
Drug: Formoterol
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • FEV1 Peak Effect Within 0 - 24 h Post-dose [ Time Frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h ] [ Designated as safety issue: No ]
    Maximum FEV1 value

  • E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. [ Time Frame: 22- 26 h post dose ] [ Designated as safety issue: No ]
    Residual FEV1 24 h post-dose

  • S-potassium, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min,1h, 2h, 4h ] [ Designated as safety issue: No ]
    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.

  • S-potassium, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min,1h, 2h, 4h ] [ Designated as safety issue: No ]
    Average S-potassium concentration


Secondary Outcome Measures:
  • FEV1 Effect at 5 Min Post-dose [ Time Frame: 5min ] [ Designated as safety issue: No ]
    FEV1 at 5 minutes

  • FEV1 Average Effect Over 0 - 24 h Post-dose [ Time Frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h ] [ Designated as safety issue: No ]
    FEV1 average effect over 24 h dosing interval

  • FEV1 Average Effect Over 0 - 12 h Post-dose [ Time Frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h ] [ Designated as safety issue: No ]
    FEV1 average effect over 12 h day-time period

  • FEV1 Average Effect Over 12 - 24 h Post-dose [ Time Frame: 12h, 14h, 18h, 22h, 24h ] [ Designated as safety issue: No ]
    FEV1 average effect over 12 h night-time period

  • Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum SBP value over 4 h

  • Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Average SBP value over 4 h

  • Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Minimum DBP value over 4 h

  • Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Average DBP value over 4 h

  • Pulse, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum pulse over 4 h

  • Pulse, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Average pulse over 4 h

  • Heart Rate, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum heart rate over 4 h

  • Heart Rate, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Average heart rate over 4 h

  • QTcB, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum QTc Bazett over 4 h

  • QTcB, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 30min, 2h, 4h ] [ Designated as safety issue: No ]
    Average QTc Bazett over 4 h

  • Tremor, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min, 1h, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

  • Tremor, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min, 1h, 2h, 4h ] [ Designated as safety issue: No ]
    Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

  • Palpitations, Peak Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min, 1h, 2h, 4h ] [ Designated as safety issue: No ]
    Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

  • Palpitations, Average Effect Over 0 - 4 h Post-dose [ Time Frame: 0, 15min, 30min, 1h, 2h, 4h ] [ Designated as safety issue: No ]
    Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

  • Plasma AZD3199 Cmax [ Time Frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h ] [ Designated as safety issue: No ]
    Maximum plasma concentration of AZD3199 measured

  • Plasma AZD3199 AUC0-24 [ Time Frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h ] [ Designated as safety issue: No ]
    Area under the plasma concentration curve from time 0 to 24 h post-dose


Enrollment: 37
Study Start Date: August 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Oxis
Active Comparator: crossover dose 6
Formoterol 36 microgram
Drug: Formoterol
Dry powder for inhalation, single dose
Other Name: Oxis

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00736489

Locations
Denmark
Research Site
Hvidovre, Denmark
Sweden
Research Site
Gothenburg, Sweden
Research Site
Lulea, Sweden
Research Site
Lund, Sweden
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Prof Leif Bjermer, MD, PhD University Hospital in Lund, Sweden
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00736489     History of Changes
Other Study ID Numbers: D0570C00007, ToBe
Study First Received: August 15, 2008
Results First Received: November 30, 2010
Last Updated: May 8, 2014
Health Authority: Sweden: Regional Ethical Review Board
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency

Keywords provided by AstraZeneca:
Asthma
airway obstruction
beta2-agonist
efficacy
inhalation

Additional relevant MeSH terms:
Airway Obstruction
Asthma
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Formoterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014