Batefenterol/Fluticasone Furoate in Treatment of Chronic Obstructive Pulmonary Disease

NCT02573870 | Completed Phase 2 Results

• 1 other identifier: 201546
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 10

Brief Summary

Batefenterol inhalation powder is currently under development as a fixed-dose combination with fluticasone furoate (FF) for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The present study will administer batefenterol/FF (300/100 micrograms \[mcg\]) for the first time to subjects with COPD, to investigate the safety and tolerability of the combination compared with placebo, and to evaluate the pharmacokinetics and pharmacodynamics profiles of the individual components when administered in combination. This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, parallel group study. Subjects will be randomized (2:1) to one of the following double-blind treatment groups: Batefenterol/FF 300/100 mcg inhalation powder once daily, or matching placebo inhalation powder once daily. Subjects will self-administer the study treatments once daily (QD) in the morning for 42 days via a multi-dose dry powder inhaler (DPI) which contains two blister strips. Additionally, an inhaled short acting beta2-receptor agonist, albuterol will be provided from screening to the end of the treatment period for all subjects to use as needed to relieve COPD symptoms. At the end of the treatment period, subjects can resume conventional therapy. The study will randomize approximately 60 subjects. The total duration of subject participation (from screening to follow-up) will be approximately 8 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD; DPI; Batefenterol; Fluticasone Furoate

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 0 to 4 Hours Post-dose Weighted Mean Heart Rate at Day 42, Derived From Electrocardiograms (ECGs)

  ECG measurements were taken in supine position after obtaining vital signs. Weighted mean was derived by calculating the area under the curve (AUC), and then dividing by the relevant time interval. Baseline was the pre-dose measurement on Day 1. Change from Baseline in 0 to 4 hours post-dose weighted mean heart rate was measured on Days 1, 28 and 42 and was analyzed using a mixed models repeated measures (MMRM) model. Intent-To-Treat (ITT) Population: all randomized participants who received at least one dose of study medication.

  Baseline and Day 42

Study Arms (2)

Batefenterol + Fluticasone Furoate

EXPERIMENTAL

Subjects will self-administer batefenterol/fluticasone furoate 300/100 micrograms inhalation powder once daily for 42 days. Albuterol will be provided from screening to Day 42, to use as needed for symptom relief.

Drug: Batefenterol + Fluticasone Furoate; Drug: Albuterol

Placebo

PLACEBO COMPARATOR

Subjects will self-administer matching placebo inhalation powder once daily for 42 days. Albuterol will be provided from screening to Day 42, to use as needed for symptom relief.

Drug: Placebo; Drug: Albuterol

Interventions

Batefenterol + Fluticasone Furoate DRUG

Batefenterol and Fluticasone Furoate (FF) will be provided as a fixed-dose combination in a dry powder inhaler (DPI), for oral inhalation once every morning, for 42 days. The DPI will consist of 2 strips of 30 blisters each, containing 300 microgram (mcg) batefenterol per blister in one strip and 100 mcg FF per blister in another strip. Both drugs will be available in a micronized form, blended with lactose monohydrate.

Batefenterol + Fluticasone Furoate

Placebo DRUG

Placebo will be provided in a DPI, for oral inhalation once every morning, for 42 days. The DPI will consist of 2 matching strips of 30 blisters each, with each blister containing lactose monohydrate and no active pharmaceutical ingredient.

Placebo

Albuterol DRUG

Albuterol inhalation will be provided as an open-label rescue medication to use as needed, to relieve chronic obstructive pulmonary disease (COPD) symptoms.

Batefenterol + Fluticasone Furoate; Placebo

Eligibility Criteria

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

You may qualify if:

• Type of subject: Outpatient.
• Informed Consent: Capable of giving signed informed consent, which includes compliance with pre-specified requirements and restrictions.
• Age and gender: Male and female subjects, 40 years of age or older at the time of signing the informed consent, are eligible to participate in the study.
• Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as:
• Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• Reproductive potential and agrees to follow one of the options listed below 30 days prior to the first dose of study medication and until at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study medication and completion of the follow-up visit. This list does not apply to females of reproductive potential with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis:
• Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label Oral Contraceptive, either combined or progestogen alone Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Chronic Obstructive Pulmonary Disease (COPD): An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
• COPD Disease severity: A post-albuterol forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of =\<0.70 and a post-albuterol FEV1 \>=30 and =\<80% of predicted normal values calculated using the European Respiratory Society Global Lung Function Initiative reference equations at Visit 1.
• Smoking history: Current or former cigarette smokers with a history of cigarette smoking of \>= 10 pack-years at Visit 1. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
• Number of pack years = (number of cigarettes per day / 20) x number of years smoked (for example, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years).
• Note: Pipe and cigar use cannot be used to calculate pack-year history.

You may not qualify if:

• Asthma: A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
• Poorly controlled COPD: defined as the occurrence of 'acute worsening of COPD that is managed with corticosteroid and/or antibiotics or that requires treatment prescribed by a physician in the 6 weeks prior to Screening (Visit 1)', or 'subjects who are hospitalized due to acute worsening of COPD within 12 weeks of Visit 1'.
• History of COPD exacerbation: subject who have had more than one exacerbation (moderate or severe) within the 12 months prior to Visit 1.
• Pneumonia and lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1; or subjects hospitalized due to pneumonia within 12 weeks of Visit 1.
• Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (for example, albuterol) via nebulized therapy.
• Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.
• Clinically significant abnormal laboratory finding at Visit 1.
• Liver Disease: Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid polymerase chain reaction test is obtained.
• Abnormal and clinically significant findings from 12-lead electrocardiogram (ECG) performed at Visit 1. Site investigators will be provided with ECG over-read conducted by a centralized independent cardiologist, to assist in evaluation of subject eligibility. For this study, an abnormal and clinically significant ECG that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following:
• Medication Prior to Spirometry: Unable to withhold albuterol for the 4 hour period required prior to spirometry testing at each study visit.
• Excluded Medications: Use of the following medications are not permitted within the defined time intervals prior to Visit 1 and throughout the study:
• Depot corticosteroids: 12 weeks Systemic, oral or parenteral corticosteroids: 6 weeks Antibiotics (for lower respiratory tract infection): 6 weeks 'Cytochrome P450 3A4' strong inhibitors and 'P-glycoprotein' inhibitor: 4 weeks Long acting beta-agonist (LABA)/inhaled corticosteroid (ICS) combination products : 4 weeks ICS : 4 weeks Phosphodiesterase 4 (PDE4) inhibitors (roflumilast): 1 week LABA/ Long-acting muscarinic antagonist (LAMA) combination (for example, vilanterol/umeclidinium bromide): 1 week Once-daily beta2-agonist (for example, Olodaterol and Indacaterol): 1 week LAMA (tiotropium, aclidinium, glycopyrronium, umeclidinium): 1 week Theophylline preparations: 48 hours Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton): 48 hours Oral beta2-agonists Long-acting: 48 hours Short-acting: 12 hours Inhaled LABA (for example, Salmeterol, formoterol): 48 hours Inhaled sodium cromoglycate or nedocromil sodium: 24 hours Inhaled short acting beta2-agonists: 4 hours Inhaled short-acting anticholinergics: 4 hours Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products: 4 hours Use of study provided albuterol is permitted during the study, except in the 4-hour period prior to spirometry testing
• Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
• Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta-2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) lactose/milk protein, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction, that, in the opinion of the study physician contraindicates study participation or use of an inhaled LAMA, LABA or ICS

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (10)

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

Hollywood, Florida, 33021, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28207, United States

Location

GSK Investigational Site

Gastonia, North Carolina, 28054, United States

Location

GSK Investigational Site

Grove City, Ohio, 43123, United States

Location

GSK Investigational Site

Easley, South Carolina, 29640, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Seneca, South Carolina, 29678, United States

Location

GSK Investigational Site

McKinney, Texas, 75069, United States

Location

Related Publications (1)

• Crim C, Gotfried M, Spangenthal S, Watkins M, Emmett A, Crawford C, Baidoo C, Castro-Santamaria R. A randomized, controlled, repeat-dose study of batefenterol/fluticasone furoate compared with placebo in the treatment of COPD. BMC Pulm Med. 2020 May 4;20(1):119. doi: 10.1186/s12890-020-1153-7.

  PMID: 32366249 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

batefenterol; fluticasone furoate; Albuterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 12, 2015
• Study Start: December 1, 2015
• Primary Completion: July 5, 2016
• Study Completion: July 5, 2016
• Last Updated: July 21, 2020
• Results First Posted: March 28, 2017

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (10)