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: February 21, 2014
Last verified: February 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
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

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: February 21, 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
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014