To Assess the Safety, Tolerability, and Pharmacokinetics of AZD7624 in Healthy Volunteers and COPD Patients

Study Overview
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Brief Summary
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This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD7624 in healthy subjects and patients with chronic obstructive pulmonary disease.

Detailed Description
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A Phase I, Randomized, DoubleBlind Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Inhaled Doses (MAD) of AZD7624 to Healthy Subjects and Patients with COPD

Official Title
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A Phase I, Randomized, DoubleBlind Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Inhaled Doses (MAD) of AZD7624 to Healthy Subjects and Patients With COPD

Conditions
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COPD, Healthy Subjects

Intervention / Treatment
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* Drug: AZD7624
* Drug: Placebo to match


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. Provision of signed and dated, written informed consent prior to any study specific procedures Plasma myoglobin and CK not above the upper reference range of the analysing laboratory at Day -1 Male and/or female patients with COPD aged above18 years with suitable veins for cannulation or repeated venipuncture. Clinical diagnosis of COPD for more than 1 year at Visit 1, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines Exclusion Criteria: Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the IP Receipt of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study that included drug treatment within at least 3 months of the first administration of the IP in this study Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Groups 1-4 multiple ascending doses of AZD7624 Healthy subjects will participate in groups 1-3. In each group 6 subjects will receive AZD7624 and 2 will receive matching placebo. COPD patients will participate in group 4. In this group, 8 patients will receive AZD7624 and 2 patients will receive matching placebo. | Drug: AZD7624<br>* Multiple ascending doses (starting from 300 µg lung deposited dose up to 1200 µg) inhaled IMP via a nebulizer<br>|
| Placebo Comparator: 2<br>Groups 1-4 multiple ascending doses of placebo Healthy subjects will participate in groups 1-3. In each group 6 subjects will receive AZD7624 and 2 will receive matching placebo. COPD patients will participate in group 4. In this group, 8 patients will receive AZD7624 and 2 will receive matching placebo. | Drug: Placebo to match<br>* Multiple doses inhaled placebo via a nebulizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Summary of number of subjects who had at least one adverse event in any category (Safety analysis set) | Up to 24 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Pharmacokinetic Parameters (AUC(0-tau) ) | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. *AUC(0-tau) = AUC(0-last) where for cohorts 2,3,4,5 and 6 tau=24 hours and for cohort 1, tau=12 hours . Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | 
| Summary of Pharmacokinetic Parameters (Cmax) | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | 
| Summary of Pharmacokinetic Parameters (Cmin) | Summary of pharmacokinetic parameters of AZD7624 after multiple once daily dose administration in cohorts 4,5,6 and multiple twice daily administration in cohorts 1,2 and 3, on Days 7, 8 or 9. Results are presented for cohort 1,2,3,4,5 with SPIRA device and for cohort 6 with ADI device (test device). Number of Participants Analyzed is based on the available data for the used device and for the day that PK measurements were taken. | PK concentration was measured at 0, 15min, 30min, 45min, 1hr, 2hr, 4hr, 6hr, 9hr, 12hr, 18hr and 24hr post dose on Day 7 for cohort 6, Day 8 for cohorts 1,4 and 5 and on Day 9 for cohorts 2 and 3. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1,, Safety,, Tolerability,, Healthy,, COPD patients