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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: AZD3199
* Drug: AZD3199
* Other: AZD3199 Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, patients, lung function