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Pulmonary Disease, Chronic ObstructivePhase 2NCT02570165

Dose-Finding Study of Batefenterol (GSK961081) Via Dry Powder Inhaler in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Phase 2 study testing Batefenterol and Umeclidinium/ Vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 25 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Batefenterol is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule. This is a multicenter, randomized, placebo-controlled, double-blind, parallel group study primarily designed to assess the dose response, efficacy and safety of five dose regimens of batefenterol… Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
Batefenterol and Umeclidinium/ Vilanterol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
325 participants
Where
25 sitesin 3 countries
Study dates
6 Nov 2015to 6 Jul 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Type of subject: Outpatient
  • Informed Consent: A signed and dated written informed consent prior to study participation
  • Age: 40 years of age or older at Visit 1.
  • Gender: Male and female subjects are eligible to participate in the study. Female subjects are eligible to participate if 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 postmenopausal status prior to study enrolment.
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  • 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 <1 percent (%) rate of failure per year, as stated in the product label Intrauterine device or intrauterine system that meets <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 subjects 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.
  • Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.
  • Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years. 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 (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years). Note: pipe and cigar cannot be used to calculate pack-year history.
  • Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <=0.70 and a post-albuterol/salbutamol FEV1 >=30 and <=70% of predicted normal at Visit 1.
  • Note: Percent predicted will be calculated using the European Respiratory Society Global Lung Function Initiative reference equations.

Who cannot join

  • Asthma: Subjects with a current diagnosis of asthma. (subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
  • Other Respiratory Disorders: Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension unrelated to COPD, and interstitial lung disease. Allergic rhinitis is not exclusionary.
  • Other Diseases/Abnormalities: Any significant diseases (including uncontrolled hypertension, diabetes and thyroid disease) that in the opinion of the investigator or the study medical monitor would put the safety of the subject at risk through study participation, or which would affect study analyses if the diseases/condition exacerbated during the study.
  • Hepatitis: Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening Visit 1 or within 3 months prior to first dose of study treatment. (subjects with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) polymerase chain reaction (PCR) test is obtained).
  • Liver Disease: Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Cancer: A current malignancy or previous history of cancer in remission for <5 years prior to Visit 1 (localised basal cell or squamous cell carcinoma of the skin that has been resected is not exclusionary.) Any current or previous history of throat cancer.
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  • Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in the 6 months prior to Visit 1 the subject will not be eligible for the study.
  • Drug Allergy: A history of hypersensitivity or allergy to any beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or lactose/milk protein, which in the opinion of the investigator or GlaxoSmithKline (GSK) medical monitor contraindicates study participation.
  • Diseases Preventing Use of Anticholinergic: Medical diagnosis of narrow- angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholinergic.
  • 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: Subjects 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.
  • Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.
  • 12-lead ECG: An abnormal and clinically significant 12-lead electrocardiogram (ECG). 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 the criteria mentioned in the protocol.
  • Screening Labs: Clinically significant abnormal finding from clinical chemistry or hematology tests at Visit 1.
  • Medication Prior to Spirometry: Unable to with hold albuterol/salbutamol 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), antibiotics (for lower respiratory tract infection) (6 weeks), cytochrome P450 3A4 strong inhibitors and P-glycoprotein inhibitors (4 weeks), systemic, oral or parenteral corticosteroids (2 weeks), inhaled corticosteroids (ICS) or long-acting beta2- agonist (LABA)/ ICS combination products (2 weeks), phosphodiesterase 4 (PDE4) inhibitor (roflumilast) (2 weeks), LABA/ long acting muscarinic receptor antagonist (LAMA) combination (eg vilanterol /umeclidinium bromide) (2 weeks), Once-daily beta2-agonist ( eg Olodaterol and Indacaterol) (10 days), long acting muscarinic antagonists (eg tiotropium, aclidinium, glycopyrronium, umeclidinium) (7 days), theophyllines (48 h), oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 h), oral beta2-agonists long-acting (48 h), short-acting (12 h), inhaled long acting beta2-agonists (LABA, e.g. salmeterol, formoterol, indacaterol) (48 h), inhaled sodium cromoglycate or nedocromil sodium (24 h), inhaled short acting beta2-agonists (4 h), inhaled short-acting anticholinergics (4 h), inhaled short-acting anticholinergic/ short-acting beta2-agonist combination products (4 h), any other investigational medication (30 days or within 5 drug half-lives [whichever is longer]).
  • The complete list of excluded cytochrome P450 inhibitors and P-glycoprotein inhibitors will be provided in study reference manual (SRM).
  • Use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing.
  • Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 h a day. As-needed oxygen use (i.e. <=12 h per day) is not exclusionary.
  • Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol) via nebulized therapy.
  • Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
  • Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
  • Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
  • Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study
  • Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
  • Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a diary.

Trial locations and contacts

25 sites in 3 countries.

25 sites in 3 countries

United States9 sites

  • GSK Investigational Site

    Anderson, South Carolina, 29621

  • GSK Investigational Site

    Baltimore, Maryland, 21225

  • GSK Investigational Site

    Greenville, South Carolina, 29615

  • GSK Investigational Site

    Hialeah, Florida, 33013

  • GSK Investigational Site

    Medford, Oregon, 97504

  • GSK Investigational Site

    Simpsonville, South Carolina, 29681

  • GSK Investigational Site

    Spartanburg, South Carolina, 29303

  • GSK Investigational Site

    St Louis, Missouri, 63141-6361

  • GSK Investigational Site

    Union, South Carolina, 29379

Other trials in United States

Germany8 sites

  • GSK Investigational Site

    Berlin, 10119

  • GSK Investigational Site

    Berlin, 10717

  • GSK Investigational Site

    Berlin, 10787

  • GSK Investigational Site

    Großhansdorf, Schleswig-Holstein, 22927

  • GSK Investigational Site

    Hamburg, 22299

  • GSK Investigational Site

    Lübeck, Schleswig-Holstein, 23552

  • GSK Investigational Site

    Rüdersdorf, Brandenburg, 15562

  • GSK Investigational Site

    Wiesbaden, Hesse, 65187

Other trials in Germany

South Africa8 sites

  • GSK Investigational Site

    Bellville, 7530

  • GSK Investigational Site

    Bloemfontein, 9301

  • GSK Investigational Site

    Meyerspark/ Pretoria, 184

  • GSK Investigational Site

    Middelburg, Mpumalanga, 1050

  • GSK Investigational Site

    Mowbray, 7700

  • GSK Investigational Site

    Port Elizabeth, Eastern Cape, 6001

  • GSK Investigational Site

    Somerset West, 7130

  • GSK Investigational Site

    Thabazimbi

Other trials in South Africa

About this study

Official title: Study 201012: A Dose-Finding Study of Batefenterol (GSK961081) Via Dry Powder Inhaler in Patients With COPD

Batefenterol is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule. This is a multicenter, randomized, placebo-controlled, double-blind, parallel group study primarily designed to assess the dose response, efficacy and safety of five dose regimens of batefenterol administered via the dry powder inhaler (DPI) once-daily in the morning for 42 days in subjects with COPD. The information obtained from this study will be used to select the minimal, optimally effective and safe dose of batefenterol and also to evaluate the pharmacokinetic profile and established pharmacodynamic (PD) responses of batefenterol. These data will support for future studies with batefenterol in COPD subjects.

The study will consist of a pre-screening visit, screening visit; a run-in period (2 weeks), treatment period of 42 days and a follow-up visit 7 days post-treatment. The total duration of the study for each subject will be approximately 9 weeks. Approximately 460 subjects will be screened in order to randomize approximately 320 subjects, assuming that 280 subjects will complete the study. During treatment period, subjects will be randomized to one of the following treatments delivered via DPI once daily in the morning: Batefenterol 37.5 mcg, 75 mcg, 150 mcg, 300 mcg and 600 mcg, umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg and placebo. All subjects will receive supplemental albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study.

Being tested
Batefenterol, Umeclidinium/ Vilanterol, Placebo
Keywords
efficacy, dry powder inhaler, vilanterol, batefenterol
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BatefenterolDrug

    Batefenterol will be provided as dry white powder for inhalation via a DPI with 30 doses (2 strips with 30 blisters per strip). First strip will contain lactose and the second strip will contain batefenterol blended with lactose with a unit dose strength of 37.5 mcg, 75 mcg, 150 mcg, 300 mcg, or 600 mcg per blister

  • Umeclidinium/ VilanterolDrug

    Umeclidinium/Vilanterol will be provided as dry white powder for inhalation via a DPI with 30 doses (2 strips with 30 blisters per strip). First strip will contain umeclidinium blended with lactose and magnesium stearate with a unit dose strength of 62.5 mcg per blister and the second strip will contain vilanterol blended with lactose and magnesium stearate with a unit dose strength of 25 mcg per blister

  • PlaceboDrug

    Placebo will be provided as dry white powder for inhalation via a DPI with 30 doses (2 strips with 30 blisters per strip) containing lactose

Study groups in NCT02570165
Study groupRoleWhat they receive
Batefenterol 37.5 mcgExperimentalEach subject will receive batefenterol 37.5 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Batefenterol
Batefenterol 75 mcgExperimentalEach subject will receive batefenterol 75 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Batefenterol
Batefenterol 150 mcgExperimentalEach subject will receive batefenterol 150 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Batefenterol
Batefenterol 300 mcgExperimentalEach subject will receive batefenterol 300 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Batefenterol
Batefenterol 600 mcgExperimentalEach subject will receive batefenterol 600 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Batefenterol
UMEC/VI 62.5/25 mcgExperimentalEach subject will receive UMEC/VI 62.5/25 mcg (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Umeclidinium/ Vilanterol
PlaceboExperimentalEach subject will receive placebo (1 actuation) once daily via DPI in the morning for 42 days of treatment period.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose at Day 42

    FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath. Weighted-mean change from Baseline was the weighted-mean FEV1 on Day 42 minus Baseline where Baseline is defined as the average of Day1 pre-dose FEV1 measured at -30 minutes and 0 minutes. The 0-6 hour (Hr.) serial FEV1 was collected at Day 1 (Visit 2) and Day 42 (Visit 6). The weighted-mean was derived by calculating the area under the curve (AUC) of FEV1 over the 6 hour period, and then dividing it by the 6-hour time interval. Batefenterol dose for each individual was compared with placebo or UMEC/VI. The change from Baseline in FEV1 was statistically analyzed using Bayesian Emax modeling of the dose response curve. Intent-to-Treat (ITT) Population comprised of all participants randomized to treatment and who received at least one dose of study medication. Participants with FEV1 values available at Baseline and Day 42 were analyzed.

    Measured: Baseline and Day 42

Secondary outcomes (1)

  1. Change From Baseline in Trough FEV1 at Day 42

    Trough FEV1 at Day 42 is the mean volume of air that can be forced out in one second after taking a deep breath at the approximately 23 Hrs and 24 Hrs assessments after the last administration of study drug. Batefenterol dose for each individual was compared with placebo or UMEC/VI. Change from Baseline was calculated as trough FEV1 on Day 42 minus baseline, where Baseline is defined as the average of Day1 pre-dose FEV1 measured at -30 minutes and 0 minutes. The Maximum Likelihood Estimation (MLE) method of dose response modeling with Emax modeling without Bayesian priors was used. Participants with FEV1 values available at Baseline and Day 42 after 24 hrs after the last administration of study drug were analyzed.

    Measured: Baseline and Day 42

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2015 (estimated)
  2. Study start6 Nov 2015
  3. Primary completion6 Jul 2016
  4. Study completion6 Jul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
325 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02570165
Sponsor's protocol ID
201012
Other IDs
2015-001409-15, 2015
Status last verified
Jun 2019
First submitted
5 Oct 2015
Last updated
16 Jul 2019
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Crim C, Watkins ML, Bateman ED, Feldman GJ, Schenkenberger I, Kerwin EM, Crawford C, Pudi K, Ho S, Baidoo C, Castro-Santamaria R. Randomized dose-finding study of batefenterol via dry powder inhaler in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2019 Mar 8;14:615-629. doi: 10.2147/COPD.S190603. eCollection 2019.

    PubMed 30880951

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Batefenterol and Umeclidinium/ Vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 25 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Germany, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose at Day 42 (time frame: Baseline and Day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02570165, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2019.

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