A Study to Evaluate the Efficacy and Safety of Losmapimod in Subjects with COPD who Frequently Exacerbate.

Phase 1

• Conditions: Chronic Obstructive Pulmonary Disease; MedDRA version: 17.0Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-002992-27-ES
• Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-16
• Last Update Posted: 5 September 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. COPD diagnosis and severity:
-Subjects with a clinical history of COPD (established by a physician) in
accordance with the following definition by the American Thoracic
Society/European Respiratory Society [Celli, 2004], for at least 6 months prior to enrolment.
-Subjects must have evidence of airflow obstruction, defined as postbronchodilator FEV1 equal to or less than 80% of predicted normal value
calculated using NHANES III reference equation at Visit 1 [Hankinson, 1999;
Hankinson, 2010] and a FEV1 / FVC ratio <=70% at Screening (Visit 1).
Note: Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the subject has self-administered 4 inhalations (i.e., total 400/360mcg) of salbutamol/albuterol via a Metered Dose Inhaler (MDI) (use of spacer optional). The study-provided central spirometry equipment will calculate the FEV1/FVC ratio and FEV1 percent predicted values.
2. Exacerbation History: A documented history (e.g., medical record verification) in the 12 months prior to Visit 1 of ? 2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalisation or extended observation in a hospital emergency room or outpatient centre.
Note: Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.
3. Existing COPD maintenance treatment: Subject must be receiving daily
maintenance treatment for their COPD for at least 3 months prior to Screening.
Notes: Subjects receiving only PRN COPD medications are not eligible for inclusion in the study. All subjects will continue on their current SoC COPD medications throughout the entire duration of the study.
4. Tobacco use: Subjects with a current or prior history of ?10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. One pack year = 20 cigarettes smoked per day for 1 year or the equivalent. Number of pack years = (number of cigarettes per day/20) x number of years smoked.
5. Sex: Male or female subjects aged ?40 years at Screening (Visit 1).
A female subject is eligible to participate if she is of non-child bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory] or if of child-bearing potential is using a highly effective method for avoidance of pregnancy (refer to Section 4.3.1) from 30 days before the first dose, for the duration of dosing
and until 2 weeks post last-dose.
6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
7. QTc <450msec or QTc <480msec for subjects with bundle branch block
The QTc is the QT interval corrected for heart rate according to either Bazett?s formula (QTcB), Fridericia?s formula (QTcF), or another method, machine or manual overread.
-For eligibility and withdrawal, ideally the same QT correction formula will be used for all subjects. However, because this is not always possible, the same QT correction formula must be used for each individual sub

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Eosinophils: >2.0% blood eosinophils at Screening (Visit 1)
2. Concomitant medication:
- COPD Medication: Subjects currently on chronic treatment with macrolides
or Roflumilast; Long term oxygen therapy (LTOT) or nocturnal oxygentherapy required for greater than 12 hours a day. Oxygen PRN use (i.e. <=12 hours per day) is not exclusionary.
- MATE1 inhibitors: cimetidine, pyrimethamine, trimethoprim (short course treatment with trimethoprim is allowed).
- Other medications: Chronic maintenance therapy with anti-Tumor Necrosis Factor (anti-TNF), anti-Interleukin-1 (anti-IL1), PDE4 inhibitors, or any other immunosuppressive therapy (not including steroids) within 60 days prior to dosing .
- Any other investigational drug within 30 days or 5 half lives, whichever is
longer prior to Screening Visit.
3. Other respiratory disorders: Subjects with asthma (as primary diagnosis) lung cancer, bronchiectasis, active sarcoidosis, active lung fibrosis, cystic fibrosis, idiopathic pulmonary hypertension, active interstitial lung diseases or other active pulmonary diseases. Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD.
4. Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device.
5. Subjects who require a non-invasive positive pressure ventilation (NIPPV) device (Note: Use of NIV in hospital as part of the medical management of an acute exacerbation is permitted.)
6. Lung resection: Subjects who have undergone previous lung reduction surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction).
7. COPD stability: Less than 30 days prior to Visit 1 have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation.
8. Evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD on chest X-ray (posteroanterior with lateral) or CT scan (historic data up to 1 year may be used).
9. 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.
10. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
11. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
12. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Subjects that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).
13. Other diseases/abnormalities: History or current evidence of clinically significant or uncontrolled cardiovascular, pulmonary, metabolic, neurological, endocrine (including uncontrolled diabetes or thyroid disease), renal, hepatic, haematological (including agranulocytosis) or gastrointestinal conditions that are uncontrolled on permitted therapy and in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial or which would
affect the efficacy or safety analysis if the disease/condition exacerbated during the study
14. Viral infections: Presence of hepatitis B sur

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified