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

• ClinicalTrials.gov Identifier: NCT01817855
• Recruitment Status: Completed
• First Posted: March 26, 2013
• Results First Posted: March 30, 2016
• Last Update Posted: March 30, 2016
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COPD; Healthy Subjects	Drug: AZD7624; Drug: Placebo to match	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Study Start Date: September 2013
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; 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; Multiple ascending doses (starting from 300 µg lung deposited dose up to 1200 µg) inhaled IMP via a nebulizer
Placebo Comparator: 2; 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; Multiple doses inhaled placebo via a nebulizer

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: Up to 24 days ]
   Summary of number of subjects who had at least one adverse event in any category (Safety analysis set)

Secondary Outcome Measures :

1. Summary of Pharmacokinetic Parameters (AUC(0-tau) ) [ Time Frame: 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 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.

2. Summary of Pharmacokinetic Parameters (Cmax) [ Time Frame: 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 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.

3. Summary of Pharmacokinetic Parameters (Cmin) [ Time Frame: 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 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United Kingdom

Research Site

London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Saeed Khan, MBBS, MRCP; Quintiles Drg Research Centre At Guys Hosipital, 6 Newcomen Street London SE1 1YR
• Study Chair: Naimish Patel, MD; AstraZeneca, Wilmington, US

More Information

Additional Information:

CSR Synopsis 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01817855
• Other Study ID Numbers: D2550C00002
• First Posted: March 26, 2013
• Results First Posted: March 30, 2016
• Last Update Posted: March 30, 2016
• Last Verified: February 2016

Keywords provided by AstraZeneca:

Phase 1,; Safety,; Tolerability,; Healthy,; COPD patients

Additional relevant MeSH terms:

AZD7624; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action