Evaluation of the Pharmacokinetics and the Pharmacodynamics of Different Dry Powder Inhalation Formulations of AZD3199 in Patients With Asthma

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Multicentre, 6-way Crossover, Single-dose, Phase IIa Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Different Dry Powder Inhalation Formulations of AZD3199 Administered Via Single Inhalation Device Compared to AZD3199 Administered Via Turbuhaler™ Inhaler in Patients With Asthma

The purpose of this study is to evaluate the pharmacokinetics and pharmacodynamics of single doses of three different dry powder inhalation formulations of AZD3199 administered via Single Inhalation Device (SID) compared to AZD3199 administered via Turbuhaler™ Inhaler and compared to placebo in patients with persistent asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: AZD3199; Drug: AZD3199; Other: AZD3199 Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden
    • Research Site
  • Luleå, 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:

• Provision of signed and dated written informed consent prior to any study specific procedures
• Men or women, age ≥ 18 years. Women must be of non-childbearing potential or stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen contraceptive method throughout the study.
• Be a non-smoker or ex-smoker who has stopped smoking for >6 months prior to study start
• A history of asthma for at least 6 months.
• Body Mass Index (BMI) 19-30 kg/m2

Exclusion Criteria:

• Significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the result of the study, or the patient's ability to participate in the study
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to β2-agonists in general or to AZD3199 and/or excipients
• Prolonged QTcF > 450 msec or shortened QTcF <340 msec
• History of alcohol/drug abuse or excessive intake of alcohol as judged by the Investigator
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD3199 800 µg inhaled via single inhaler device (SID), single dose	Drug: AZD3199; Inhaled via single inhaler device (SID); Drug: AZD3199; Inhaled via Turbuhaler inhaler
Experimental: 2; AZD3199 880 µg inhaled via SID, single dose	Drug: AZD3199; Inhaled via single inhaler device (SID); Drug: AZD3199; Inhaled via Turbuhaler inhaler
Experimental: 3; AZD3199 1400 µg inhaled via SID, single dose	Drug: AZD3199; Inhaled via single inhaler device (SID); Drug: AZD3199; Inhaled via Turbuhaler inhaler
Experimental: 4; AZD3199 300 µg inhaled via Turbuhaler inhaler, single dose	Drug: AZD3199; Inhaled via single inhaler device (SID); Drug: AZD3199; Inhaled via Turbuhaler inhaler
Experimental: 5; AZD3199 1200 µg inhaled via Turbuhaler inhaler, single dose	Drug: AZD3199; Inhaled via single inhaler device (SID); Drug: AZD3199; Inhaled via Turbuhaler inhaler
Placebo Comparator: 6; Placebo inhaled via Turbuhaler inhaler and SID, single dose	Other: AZD3199 Placebo; Inhaled via Turbuhaler inhaler and SID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emax: Maximum Value of FEV1 for Every Treatment Visits	Peak effect (Emax) within 0-24 hours of FEV1, for treatment visits 2 to 7.	0-24 hrs
E22-26h: The Average of the FEV1 Values Between 22 and 26 h for Every Treatment Visit	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.	22-26 hrs.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tEmax: Time to Maximum Value of FEV1 for Every Treatment Visit	Time to peak effect (tEmax), within 0-24 hours of FEV1, for treatment visits 2 to 7.	0 - 24 hrs.
E5min: The Value of FEV1 at 5 Min for Every Treatment Visit.	Onset of effect (E5min), observed at 5 min. FEV1 for treatment visits 2 to 7.	FEV1 at 5 min
E0-24h: The Average of the FEV1 Values Between 0 and 24 h for Every Treatment Visit	Average effect over 0-24 hours of FEV1 (E0-24h), for treatment visits 2 to 7.	0 - 24 hrs
Emax: Maximum Value of Pulse for Every Treatment Visits	Peak effect (Emax) within 0-4 hours of pulse, for treatment visits 2 to 7.	0 - 4 hrs.
E0-4h: The Average of the Pulse Values Between 0 and 4 h for Every Treatment Visit	Average effect (E0-4h) of Pulse, for treatment visits 2 to 7.	0 - 4 hrs.
Cmax: Maximum Plasma Concentration	Maximum plasma concentration (Cmax) for AZD3199 doses	0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.
AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC),	Area under the plasma concentration-time curve from zero to infinity (AUC), for AZD3199 doses	0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.
Tmax:Time to Maximum Plasma Concentration	Time to maximum plasma concentration (tmax), for AZD3199 doses	0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.
t1/2 :Terminal Half-life	Terminal half-life (t1/2),for AZD3199 doses	0 - 120 hrs for first two treatment visit 2 and 3 and 0 - 48 hrs for other treatment visits.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: May 3, 2011
• First Submitted That Met QC Criteria: May 4, 2011
• First Posted (Estimate): May 5, 2011

Study Record Updates

• Last Update Posted (Estimate): March 5, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: lung function; Asthma; patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Agonists; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; AZD-3199
• Other Study ID Numbers: D0570C00011; 2011-000133-37 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No