Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

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

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

Study Overview

• Status: Completed
• Conditions: Asthma; Airway Obstruction
• Intervention / Treatment: Drug: AZD3199; Drug: Placebo; Drug: Formoterol

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark
    • Research Site
• Sweden
  • Gothenburg, Sweden
    • Research Site
  • Lulea, Sweden
    • Research Site
  • Lund, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Peak Effect Within 0 - 24 h Post-dose	Maximum FEV1 value	0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit.	Residual FEV1 24 h post-dose	22- 26 h post dose
S-potassium, Peak Effect Over 0 - 4 h Post-dose	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.	0, 15min, 30min,1h, 2h, 4h
S-potassium, Average Effect Over 0 - 4 h Post-dose	Average S-potassium concentration	0, 15min, 30min,1h, 2h, 4h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Effect at 5 Min Post-dose	FEV1 at 5 minutes	5min
FEV1 Average Effect Over 0 - 24 h Post-dose	FEV1 average effect over 24 h dosing interval	0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
FEV1 Average Effect Over 0 - 12 h Post-dose	FEV1 average effect over 12 h day-time period	0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h
FEV1 Average Effect Over 12 - 24 h Post-dose	FEV1 average effect over 12 h night-time period	12h, 14h, 18h, 22h, 24h
Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose	Maximum SBP value over 4 h	0, 30min, 2h, 4h
Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose	Average SBP value over 4 h	0, 30min, 2h, 4h
Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose	Minimum DBP value over 4 h	0, 30min, 2h, 4h
Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose	Average DBP value over 4 h	0, 30min, 2h, 4h
Pulse, Peak Effect Over 0 - 4 h Post-dose	Maximum pulse over 4 h	0, 30min, 2h, 4h
Pulse, Average Effect Over 0 - 4 h Post-dose	Average pulse over 4 h	0, 30min, 2h, 4h
Heart Rate, Peak Effect Over 0 - 4 h Post-dose	Maximum heart rate over 4 h	0, 30min, 2h, 4h
Heart Rate, Average Effect Over 0 - 4 h Post-dose	Average heart rate over 4 h	0, 30min, 2h, 4h
QTcB, Peak Effect Over 0 - 4 h Post-dose	Maximum QTc Bazett over 4 h	0, 30min, 2h, 4h
QTcB, Average Effect Over 0 - 4 h Post-dose	Average QTc Bazett over 4 h	0, 30min, 2h, 4h
Tremor, Peak Effect Over 0 - 4 h Post-dose	Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.	0, 15min, 30min, 1h, 2h, 4h
Tremor, Average Effect Over 0 - 4 h Post-dose	Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.	0, 15min, 30min, 1h, 2h, 4h
Palpitations, Peak Effect Over 0 - 4 h Post-dose	Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h	0, 15min, 30min, 1h, 2h, 4h
Palpitations, Average Effect Over 0 - 4 h Post-dose	Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h	0, 15min, 30min, 1h, 2h, 4h
Plasma AZD3199 Cmax	Maximum plasma concentration of AZD3199 measured	0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h
Plasma AZD3199 AUC0-24	Area under the plasma concentration curve from time 0 to 24 h post-dose	0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Bjermer L, Rosenborg J, Bengtsson T, Lotvall J. Comparison of the bronchodilator and systemic effects of AZD3199, an inhaled ultra-long-acting beta(2)-adrenoceptor agonist, with formoterol in patients with asthma. Ther Adv Respir Dis. 2013 Oct;7(5):264-71. doi: 10.1177/1753465813497527. Epub 2013 Aug 1.

Helpful Links

• Related Info
• D0570C00007 CSR Synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: August 15, 2008
• First Submitted That Met QC Criteria: August 15, 2008
• First Posted (Estimate): August 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 19, 2014
• Last Update Submitted That Met QC Criteria: May 8, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Asthma; efficacy; inhalation; airway obstruction; beta2-agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Airway Obstruction; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate; AZD-3199
• Other Study ID Numbers: D0570C00007; ToBe