A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases.

NCT03645434 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D6640C00006
• Study Type: interventional
• Target: 73
• Locations: 2 countries
• Sites: 5

Brief Summary

This study will evaluate the efficacy and safety data of AZD8871 in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will determine the 24-hour efficacy (lung function) profile of AZD8871 600 μg relative to placebo dry powder inhaler (DPI) based on trough forced expiratory volume in 1 second (FEV1) following repeated dosing (2 weeks). Anoro® Ellipta® (umeclidinium/vilanterol) once daily is included as an active control. This study aims at providing a novel approach to the treatment of COPD with greater efficacy than single-mechanism bronchodilators, equivalent to long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) administered as free- or fixed-dose combination therapies, with an equivalent or superior safety and tolerability profile.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Moderate to severe COPD; Muscarinic receptor antagonist; β2 adrenoceptor agonist (MABA); Long-acting muscarinic antagonist (LAMA); Long-acting β2-agonist (LABA); Inhaled long-acting bronchodilator; Small airways disease (obstructive bronchiolitis); Parenchymal destruction (emphysema),

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Trough FEV1 at Day 15

  To evaluate the efficacy of inhaled AZD8871 600 μg in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

  Day 15

• Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) at Day 1 to Day 8, Day 9 to Day 14, Day 1 to Day 14

  To evaluate the efficacy of inhaled AZD8871 600 μg in patients with moderate to severe COPD. At each visit, patients are asked to evaluate the impact of COPD on their wellbeing and daily life on a 6-point Likert scale ranging from 0 to 5, with higher scores indicating a higher impact of COPD. The CAT is expressed as a total score, which is a sum of the 8 questions, ranging from 0 to 40.

  Day 1 to Day 8, Day 9 to Day 14, Day 1 to Day 14

Secondary Outcomes (18)

• FEV1 AUC(0-4)/4h (Area Under the Curve for the Change in FEV1 From Baseline to 4h, Normalised by the Time Window)

  At Day 1, Day 8, and Day 14

• FEV1 AUC(0-8)/8h (Area Under the Curve for the Change in FEV1 From Baseline to 8h, Normalised by the Time Window)

  Day 1 and Day 14

• FEV1 AUC(0-12)/12h (Area Under the Curve for the Change in FEV1 From Baseline to 12h, Normalised by the Time Window)

  Day 1 and Day 14

• FEV1 AUC(0-24)/24h (Area Under the Curve for the Change in FEV1 From Baseline to 24h, Normalised by the Time Window)

  Day 1 and Day 14

• Change From Baseline in Trough FEV1 on Day 2 and Day 8.

  Day 2 and Day 8.

Study Arms (6)

Treatment sequence A

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follow: Treatment period 1: AZD8871 600 µg and Anoro® Ellipta® matching placebo. Treatment period 2: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg. Treatment period 3: Matching placebo of AZD8871 and Anoro® Ellipta®

Drug: AZD8871; Drug: Anoro® Ellipta®

Treatment sequence B

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follows: Treatment period 1: AZD8871 600 µg and Anoro® Ellipta® matching placebo. Treatment period 2: Matching placebo of AZD8871 and Anoro® Ellipta® Treatment period 3: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg.

Drug: AZD8871; Drug: Anoro® Ellipta®

Treatment sequence C

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follows: Treatment period 1: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg. Treatment period 2: AZD8871 600 µg and Anoro® Ellipta® matching placebo. Treatment period 3: Matching placebo of AZD8871 and Anoro® Ellipta®

Drug: AZD8871; Drug: Anoro® Ellipta®

Treatment sequence D

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follow: Treatment period 1: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg. Treatment period 2: Matching placebo of AZD8871 and Anoro® Ellipta® Treatment period 3: AZD8871 600 µg and Anoro® Ellipta® matching placebo.

Drug: AZD8871; Drug: Anoro® Ellipta®

Treatment sequence E

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follow: Treatment period 1: Matching placebo of AZD8871 and Anoro® Ellipta® Treatment period 2: AZD8871 600 µg and Anoro® Ellipta® matching placebo. Treatment period 3: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg.

Drug: AZD8871; Drug: Anoro® Ellipta®

Treatment sequence F

EXPERIMENTAL

Randomized patients will receive multiple oral dose of inhalation powder via DPI as follow: Treatment period 1: Matching placebo of AZD8871 and Anoro® Ellipta® Treatment period 2: AZD8871 matching placebo and Anoro® Ellipta® 55 μg / 22 μg. Treatment period 3: AZD8871 600 µg and Anoro® Ellipta® matching placebo.

Drug: AZD8871; Drug: Anoro® Ellipta®

Interventions

AZD8871 DRUG

Randomized patients will receive 14 repeated daily doses of AZD8871 600 µg inhalation powder via DPI.

Treatment sequence A; Treatment sequence B; Treatment sequence C; Treatment sequence D; Treatment sequence E; Treatment sequence F

Anoro® Ellipta® DRUG

Randomized patients will receive 14 repeated daily doses of Anoro® Ellipta® (55 µg/22 µg) inhalation powder via DPI.

Also known as: Anoro® - Umeclidinium/Vilanterol, Ellipta® - Device

Treatment sequence A; Treatment sequence B; Treatment sequence C; Treatment sequence D; Treatment sequence E; Treatment sequence F

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written ICF prior to any study-specific procedures, sampling, and analyses.
• Patient must be 40 to 85 years male and/or females of non-childbearing potential who are not pregnant/lactating at the time of signing the ICF (Screening; Visit 1).
• Patient with an established clinical history of moderate to severe COPD for more than 1 year at Screening, according to the GOLD COPD guidelines.
• Patient who is a current or former smoker (defined as one who has stopped smoking for at least 6 months prior to Screening) with a history of ≥10 pack-years of cigarette smoking \[Number of pack-years=(number of cigarettes per day/20)\* number of years smoked (eg, 1 pack-year=20 cigarettes smoked per day for 1 year)\].
• Patient with post-bronchodilator FEV1/forced vital capacity (FVC) 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 at Visit 2. 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 following the approved dosage and regimen (during run-in and wash-out periods) with or without ICS for maintenance therapy of COPD and rescue medication salbutamol (as needed) from Visit 1 to Visit 11.
• Patient must be able to read, speak and understand local language, and be willing to remain at the study centre as required per-protocol to complete all visit assessments.
• Body mass index (BMI) \<40 kg/m2 at the time of Screening.
• Female patients must be of non-childbearing potential defined as:
• 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 patients 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 IP until 3 months after the last administration of the IP. In addition to a condom with spermicide, a second highly effective method of contraception (oral, intravaginal or transdermal hormonal contraceptives, intrauterine device, intrauterine hormone-releasing system, or sexual abstinence until 3 months after the last administration of the IP) should be used with female partners of childbearing potential. Double barrier methods (a combination of male condom with either a cap, diaphragm or sponge with spermicide) are not considered to be highly effective methods of contraception. Male patients with a pregnant partner should use a condom and spermicide.

You may not qualify if:

• Patient has significant diseases other than COPD, (ie, clinically relevant disease or condition or an abnormality in prior ECGs, medical history or physical examinations) 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's ability to participate in the study.
• 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 who had 2 or more exacerbations of COPD (moderate or severe in intensity) within the last year prior to Screening (see Section 7.1 for definition of exacerbation of COPD).
• Patient has been hospitalised due to poorly controlled COPD within 3 months of the Screening period.
• Patient has acute worsening of COPD that requires treatment with corticosteroids or antibiotics in the 6 week interval prior to or during the Screening period.
• Patient has had lower respiratory tract infection(s) that required antibiotics within 6 weeks prior to the Screening period.
• Patient has significant cardiovascular disease that may be vulnerable to cardiovascular instability. Note: Some examples of clinically significant cardiovascular conditions are:
• Myocardial infarction within the 6 months prior to Screening Visit (Visit 1).
• Unstable angina or unstable arrhythmia which has required changes in the pharmacological therapy or other intervention within 12 months prior to Screening (Visit 1), or newly diagnosed arrhythmia within the previous 3 months prior to Screening (Visit 1).
• Second degree atrio-ventricular block.
• Use of pacemaker.
• Hospitalisation within 12 months prior to Screening (Visit 1) for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV per the "New York Heart Association".
• Patient with a QT interval corrected using Fridericia's formula (QTcF) value \>450 ms for male and \>470 ms for female or an ECG that is not suitable for QT measurements (eg, poorly defined termination of the T wave).

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (5)

Research Site

Berlin, 14050, Germany

Location

Research Site

Grosshansdof, 22927, Germany

Location

Research Site

Wiesbaden, 65187, Germany

Location

Research Site

London, HA1 3UJ, United Kingdom

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Singh D, Beier J, Astbury C, Belvisi MG, Da Silva CA, Jauhiainen A, Jimenez E, Lei A, Necander S, Smith JA, Wahlby Hamren U, Xin W, Psallidas I. The novel bronchodilator navafenterol: a phase 2a, multicentre, randomised, double-blind, placebo-controlled crossover trial in COPD. Eur Respir J. 2022 Apr 7;59(4):2100972. doi: 10.1183/13993003.00972-2021. Print 2022 Apr.

  PMID: 34503985 DERIVED

Related Links

• Redacted SAP.
• Redacted CSP.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Interventions

AZD-8871; vilanterol

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: AstraZeneca AB
• Organization: AstraZeneca AB

clinicaltrialtransparency@astrazeneca.com

1-877-400-4656

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study will be performed in a double-blind manner. Each investigational product (IP) and its placebo will be supplied in identical packaging to enable double-blind conditions.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 24, 2018
• Study Start: October 10, 2018
• Primary Completion: August 7, 2019
• Study Completion: August 7, 2019
• Last Updated: December 17, 2020
• Results First Posted: December 17, 2020

Record last verified: 2020-11

Locations

DE (3); GB (2)