Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Serevent Diskus
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: SALMETEROL
CAS Number: 94749-08-3
Other descriptive name: SALMETEROL XINAFOATE
Concentration unit
Sponsors
GlaxoSmithKline GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product that may impact subject eligibility is provided in the current Prescribing Information for Serevent® Diskus® (50 µg). Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Subjects with COPD of GOLD Class II or III with a post-bronchodilator spirometry forced expiratory volume in one second (FEV1) 40 and =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study (for detailed information on prohibited medications see also Protocol page 22, Table 1): 1. Women who are pregnant or lactating. 2. Subjects not willing or unable to sign the informed consent before study start. 3. Subjects with a current diagnosis of asthma. 4. Subjects with a-1 antitrypsin deficiency as the underlying cause of COPD. 5. Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. 6. Subjects with lung volume reduction surgery within the 12 months prior to Screening. 7. Subjects who have been hospitalized due to poorly controlled COPD within 6 weeks prior to the Screening Visit. 8. Subjects with poorly controlled COPD, defined as the occurrence of an exacerbation managed with systemic corticosteroids or antibiotics prescribed by a physician 6 weeks prior to the Screening Visit. 9. Frequent exacerbations necessitating the therapy with inhaled glucocorticosteroids according to the GOLD guideline. 10. COPD with nasal intermittent positive pressure ventilation (NIPPV). 11. Treatment with drugs having direct sympathomimetic activity (e.g. theophylline, moxonidine, clonidine). 12. Oral medication with beta2-sympathomimetics. 13. Inhaled therapy with sodium cromoglycate or nedocromil sodium. 14. Treatment with systemic, oral or parenteral (intra-articular) corticosteroids. 15. Treatment with strong cytochrome P450 3A4 inhibitors. 16. Treatment with any other investigational drug. 17. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen use = 12 hours per day is not exclusionary. 18. Medication prior to spirometry: Subjects who are medically unable to withhold their SABA for the 6-hour period required prior to spirometry testing at each study visit. 19. Subjects with clinically significant sleep apnoea that is uncontrolled. 20. Unstable angina pectoris or signs and history of left heart failure with a left ventricular ejection fraction 3 antihypertensive drugs. 22. Clinically evident polyneuropathy. 23. Diabetes mellitus necessitating any insulin therapy. 24. Severe concomitant disease (likely to reduce life expectancy to less than 3 years). 25. Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant neurological, psychiatric, renal, hepatic, immunological, endocrine or haematological abnormality that is uncontrolled.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate a decrease in muscle sympathetic nerve activity (MSNA) evaluated by microneurography as bursts/100 heart beats after acute administration of salmeterol in COPD subjects.;Secondary Objective: The secondary objectives are: • To evaluate if changes in MSNA after acute administration of salmeterol in COPD subjects are correlated with changes in FEV1, heart rate variability (HRV) or baroreflexes. • To evaluate changes in MSNA from Baseline after 4 weeks of salmeterol treatment in COPD subjects. • To evaluate if changes in MSNA from Baseline after 4 weeks of salmeterol treatment in COPD subjects are correlated with changes in FEV1, HRV or baroreflexes. • To assess safety and tolerability of treatment with salmeterol. • To evaluate a reduction in arterial stiffness. ;Primary end point(s): • Effect (i.e. the immediate change before versus after 1 inhalation at Visit 1) of inhaled salmeterol on MSNA evaluated as burst/100 heart beats relative to placebo. ;Timepoint(s) of evaluation of this end point: Muscle sympathetic nerve activity (MSNA) will be measured at visit 1 (week 0) and visit 2 (week 4 +/- 4 days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in MSNA (evaluated by microneurography as bursts/100 heart beats) from Baseline after 4 weeks of salmeterol treatment (Visit 2) • Changes in HRV (in the time and frequency domain) from Baseline after acute administration of salmeterol and after 4 weeks of salmeterol treatment (Visit 2) • Changes in spontaneous baroreflex sensitivity from Baseline after acute administration of salmeterol and after 4 weeks of salmeterol treatment (Visit 2) • Changes in FEV1 from Baseline after acute administration of salmeterol and after 4 weeks of salmeterol treatment (Visit 2) • VC, FRC (helium and body), TLC and RV • Resting ventilation (respiration rate and tidal volume) • Plasma norepinephrine, epinephrine and Brain Natriuretic Peptide (BNP) • Rate of subjects with diastolic dysfunction on echocardiography;Timepoint(s) of evaluation of this end point: Visit 1 and Visit 2: all of the secondary endpoints will be measured; additionally, the subjects will be contacted by phone two weeks after visit 1 to document signs and symptoms of COPD, concomitant medication, (serious) adverse events, compliance check (study medication and rescue medication). | — |
Countries
Germany
Contacts
Public ContactCTA project lead
GlaxoSmithKline GmbH & Co. KG
Outcome results
None listed