Phase 2 Completed N=323 Randomized Double-blind Treatment

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

Pulmonary Disease, Chronic Obstructive

Source: ClinicalTrials.gov NCT02570165 ↗

Enrolled (actual)

323

Serious AEs

1.6%

Results posted

Mar 2017

Primary outcomePrimary: Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose at Day 42 — -9.90; 181.20; 221.68; 251.87 Milliliters (mL)

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 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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose at Day 42	-9.90; 181.20; 221.68; 251.87; 271.47; 282.94	—
SECONDARY Change From Baseline in Trough FEV1 at Day 42	-35.7; 146.5; 160.8; 168.9; 173.2; 175.4	—

Eligibility Criteria

Inclusion Criteria

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.

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 =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 =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.

Exclusion Criteria

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 excl

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Data sourced from ClinicalTrials.gov (NCT02570165). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.