Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871

NCT02971293 | Completed Phase 2 Results

• 1 other identifier: D6640C00004
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a study to evaluate the effects of AZD8871 in patients with COPD. Adult male or female patients with moderate to severe COPD, who agree to be in this study, will receive 3 treatments, i.e. 2 different doses of AZD8871 and placebo (dummy medication containing no drug) at once a day for 2 weeks, in a random order. To make the comparison between AZD8871 and placebo as fair as possible, this study is "double blinded." This means that neither patient nor the study doctor will know in which order the 3 treatments will be given. This study will include patients who are between 40 and 80 years of age. In total there will be 42 patients participating in this study at two study centers in the United Kingdom and Germany. The study will have a total of 12 visits for each patient spanning for a period of 4 to 6 months. The study is anticipated to run for approximately 8 months and should not exceed 10 months.

Conditions

Chronic Obstructive Pulmonary Disease COPD

Keywords

AZD8871; long-acting muscarinic antagonist (LAMA); long-acting β2-agonist (LABA); inhaled long-acting bronchodilator; pharmacokinetics; safety; tolerability; efficacy; Phase IIa; Muscarinic receptor antagonist β2 adrenoceptor agonist (MABA)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)

  The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15

  On Day 15

Secondary Outcomes (26)

• Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)

  Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

• Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)

  Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

• Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)

  Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

• Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)

  Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

• AUClast of AZD8871 and Its Metabolites (Single Dose)

  Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

Study Arms (3)

AZD8871 100 µg

EXPERIMENTAL

The subjects will receive AZD8871 100 µg once daily, by dry powder inhaler (DPI) device. The treatment will be administered via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.

Drug: AZD8871 100 µg

Placebo

PLACEBO COMPARATOR

The placebo will be administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient will receive one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.

Drug: Placebo

AZD8871 600 µg

EXPERIMENTAL

The subjects will receive AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.

Drug: AZD8871 600 µg

Interventions

AZD8871 100 µg DRUG

The subjects will receive one dose of AZD8871 100 µg single dose DPI.

AZD8871 100 µg

AZD8871 600 µg DRUG

The subjects will receive AZD8871, 600 µg single dose DPI.

AZD8871 600 µg

Placebo DRUG

The subject will receive Placebo single dose DPI.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient who provided of informed consent prior to any study-specific procedures
• Male or female 40 to 80 years of age (both inclusive) at Screening (Visit 1). A female is eligible to enter and participate in the study if she is of non-childbearing potential.
• Note: A female is considered to be of non-childbearing potential if she meets one of the following criteria:
• Permanently or surgically sterilised, including hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy
• Post-menopausal; aged \<50 years and amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range of the local laboratory.
• Post-menopausal; aged ≥50 years and amenorrhoeic for 12 months or more, following cessation of all exogenous hormonal treatments.
• Male patient should use a condom and spermicide to prevent pregnancy and drug exposure of a partner, regardless of the gender or childbearing potential of the partner from the day of the first administration of the investigational product (IP) until 3 months after the last administration of the IP.
• COPD Diagnosis: Patient with an established clinical history of COPD for more than 1 year at Screening, according to the Global Initiative for Chronic Obstructive Lung Disease 2016 COPD guidelines.
• Tobacco Use: Patient is a current or former smoker with a history of ≥10 pack-years of cigarette smoking. A former smoker is defined as one who has stopped smoking for at least 6 months prior to Screening.
• Patient with post-bronchodilator FEV1/FVC (Forced vital capacity) ratio \<70% based on the value reached after inhalation of salbutamol (400 µg) at Visit 2. If criterion is not met, the test can be repeated at the latest, up to Day 14.
• Patient with post-bronchodilator FEV1 that must be ≥40% and \<80% predicted normal value and must also be \>750 mL at Visit 2. If criterion is not met, the test can be repeated at the latest, up to Day 14.
• Patient who fulfils reversibility criteria to salbutamol at Visit 2. Reversibility is defined as ≥12% and ≥200 mL increase in FEV1 after inhalation of 4 puffs of salbutamol. (400 µg). If criterion is not met, the test can be repeated at the latest, up to Day 14.
• Patient is willing and, in the opinion of the Investigator, able to change current COPD therapy as required by the protocol and willing to use ipratropium Four times a day (if needed, during run-in and wash-out periods) with or without Inhaled corticosteroid for maintenance therapy of COPD and as needed rescue salbutamol from Visit 1 up Visit 11.
• Patient is free from any clinically active disease other than COPD that may impact study outcome, as determined by medical history, physical examination, laboratory testing, and 12-lead ECG findings, at Screening.
• Patient is willing to remain at the study centre as required per protocol to complete all visit assessments.

You may not qualify if:

• Patient previously enrolled in the present study.
• Patient has significant diseases other than COPD, ie, disease or condition or an abnormality in laboratory, ECG, medical history or physical examination which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patient'spatient's ability to participate in the study.
• Childbearing potential female, pregnant or lactating.
• Patient who, in the opinion of the Investigator, has a current diagnosis of asthma.
• Patient has alpha-1 antitrypsin deficiency as the cause of COPD.
• Lung surgery for volume reduction or lung transplantation: Patient has undergone lung volume reduction surgery, lobectomy, or bronchoscopic lung volume reduction (endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, massive pulmonary embolism and airway implants) within 1 year of Screening (Visit 1).
• Patient is using nocturnal positive pressure (eg, continuous positive airway pressure or bi level positive airway pressure). Patient is using any non-invasive positive pressure ventilation device.
• Note: A patient using continuous positive airway pressure or bi level positive airway pressure for Sleep Apnoea Syndrome is allowed in the study.
• Patient has been hospitalised due to poorly controlled COPD within 3 months of Screening.
• Patient has acute worsening of COPD that requires treatment with corticosteroids or antibiotics in the 6 week interval prior to Screening (Visit 1), or during the Screening Period (between Visits 1 and 3).
• Patient has had lower respiratory tract infections that required antibiotics within 6 weeks prior to Screening.
• Patient cannot perform acceptable spirometry, ie, meet American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptability criteria.
• Patient has changed their smoking status (ie, start or stop smoking) or initiation of a smoking cessation program within 6 weeks prior to Screening.
• Patient has participated in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or who will enter the acute phase of a pulmonary rehabilitation program during the study. A patient in the maintenance phase of a pulmonary rehabilitation program is not to be excluded.
• Cardiac disease: Subject with significant cardiovascular disease cardiovascular instability. Patient with heart rate \<50 beats per minute. Patient has clinically significant uncontrolled hypertension as assessed by the investigator.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Berlin, 14050, Germany

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

AZD-8871

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Ioannis Psallidas, MD, PhD
• Organization: AstraZeneca

Information.centre@astrazeneca.com

1-877-240-9479

Study Officials

• Dave Singh, Prof

  Medicines Evaluation Unit, Manchester, United Kingdom

  PRINCIPAL INVESTIGATOR

• Rainard Fuhr, Dr

  PAREXEL International GmbH EPCU Berlin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 22, 2016
• Study Start: December 15, 2016
• Primary Completion: August 18, 2017
• Study Completion: August 18, 2017
• Last Updated: June 18, 2019
• Results First Posted: June 18, 2019

Record last verified: 2019-06

Locations

DE (1); GB (1)