Efficacy and Safety Study of Two Dose Levels of AZD2115 in Subjects With Moderate to Severe COPD

A Randomized, Double Blind, Chronic Dosing (14 Days), Three Period, Placebo Controlled, Cross Over, Multi Center Study to Assess Efficacy and Safety of Two Dose Levels of AZD2115 MDI in Subjects With Moderate to Severe COPD

This is a phase IIa dose-ranging, randomized, double-blind, chronic-dosing (14 Days), three-period, placebo-controlled, multi-center, cross-over study to assess the efficacy and safety of two dose levels of a dual pharmacology molecule with the combined properties of a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA); (AZD2115) delivered by a metered-dose inhaler (MDI) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: AZD2115 Dose 1; Drug: AZD 2115, Dose 2; Drug: Placebo MDI

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Clearwater, Florida, United States
      • Pearl Therapeutics Study Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Pearl Therapeutics Study Site
    • Spartanburg, South Carolina, United States
      • Pearl Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic Obstructive Pulmonary Disease Diagnosis: Subjects with an established clinical history of COPD for more than 1 year at Screening, according to the COPD GOLD guidelines.
• Current or former smokers with a history of ≥10 pack years of cigarette smoking.
• Post-bronchodilator FEV1/FVC ratio of <70%.
• Pre-bronchodilator FEV1 must be <80% predicted
• Women of non-child bearing potential (ie., physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or women of child bearing potential, has a negative serum pregnancy test at Screening and agrees to acceptable contraceptive methods for the duration of the study.

Exclusion Criteria:

• Pregnancy: Women who are pregnant or lactating.
• Significant diseases other than COPD, ie., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study.
• Primary diagnosis of asthma.
• Alpha-1 antitrypsin deficiency as the cause of COPD
• Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea.
• Poorly controlled COPD (hospitalization due to poorly controlled COPD within 3 months of Screening or requiring treatment with corticosteroids or antibiotics in the 6 week interval prior to Screening or during Screening.
• Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of Randomization.
• Clinically significant abnormal ECG.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD2115 Dose 1; AZD 2115, Dose 1 administered as two inhalations BID	Drug: AZD2115 Dose 1; AZD 2115, Dose 1 administered as two inhalations BID
Experimental: AZD 2115 Dose 2; AZD 2115, Dose 2 administered as two inhalations BID	Drug: AZD 2115, Dose 2; AZD 2115, Dose 2 administered as two inhalations BID
Placebo Comparator: Placebo MDI; Placebo MDI administered as two inhalations BID	Drug: Placebo MDI; Placebo MDI administered as two inhalations BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12) relative to baseline	14 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in morning pre dose trough FEV1	14 Days
Peak change in FEV1	14 Days
Forced vital capacity (FVC) AUC0-12 relative to baseline	14 Days
Peak change in FEV1	Day 1
Change from baseline in 12-hour post dose trough FEV1	14 Days
Time to onset of action	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Cmax, AUC0-12, AUC0-t, tmax, Apparent elimination half-life (t1/2), Apparent volume of distribution (Vd/F), Apparent total body clearance (CL/F)	Day 1 through Day 15
Safety	Safety will be assessed by adverse events (AEs), physical examination findings, dry mouth and tremor assessments, paradoxical bronchospasm, vital signs, electrocardiogram (ECG), and laboratory assessments.	Day1 through Day 15

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Shahid Siddiqui, MD, Pearl Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 9, 2014

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AZD2115 D3060C00006