A double-blind, randomized, cross-over, placebocontrolled, 2-part study to compare the effect of exercise and high-dose salbutamol on maximal heart-rate in patients with COPD following therapeutic doses of inhaled QAB149 and salmeterol - ND
- Conditions
- MedDRA version: 6.1Level: PTClassification code 10009026COPD
- Registration Number
- EUCTR2007-001051-19-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
1. Male and female patients age 40 to 75 years of age with a diagnosis of COPD according to GOLD criteria and >10-pack year history of smoking, a postbronchodilator FEV1 < 90% of predicted and > 0.75 L, and a post-bronchodilator FEV1/FVC < 70% 2. At screening, reversibility to 400 mcg of salbutamol >5% and <12%, and <200mL. This criterion for reversibility must be demonstrated after a washout period of at least 6 h for short-acting bronchodilators, 48 h for long-acting beta-2-agonists and 72 h for anticholinergic agents 3. Female patients must be: EITHER: Of child bearing potential and must be using a double-barrier local contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom. Females using oral contraceptives may be included providing they use a barrier method of contraception in addition. OR: Postmenopausal women must have no regular menstrual bleeding for at least 1 years prior to inclusion. Menopause will be confirmed by a plasma FSH level of >40 IU/L. Postmenopausal women taking Hormone Replacement therapy (HRT) may be included. OR: Female patients must have been surgically sterilized at least 6 months prior to screening. Surgical sterilization procedures must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. 4. Use of only short-acting inhaled β2 agonists or short-acting inhaled anti-cholinergics as needed to relieve COPD symptoms is permitted. Patients taking corticosteroids may be included if they have been on a stable regimen for at least one month prior to screening. Patients taking long-acting inhaled muscarinic antagonists may participate, if they are switched to short-acting inhaled β2 agonists and/or short acting anticholinergics at least 48 hours prior to study participation. The risk of switching a patient's medication in this case should be considered. Dosing should not be within 6 hours of their last short acting inhaled β2 agonist administration. In this case dosing may be rescheduled once. 5. At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the patient has rested in a supine position for at least three (3) minutes, and again when required after three (3) minutes in the standing position. Vital signs for supine measurements should be within the following ranges (treated or untreated): oral body temperature between 35.0-37.5 ?C systolic blood pressure, 90-165 mm Hg diastolic blood pressure, 50-95 mm Hg pulse rate, 40 - 90 bpm All blood pressure measurements at other time-points should be assessed with the patient seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination. PLS SEE PROTOCOL
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
significant medical condition that in the opinion of the Investigator may compromise patient safety, patient compliance, interfere with evaluations, or preclude completion of the trial.. Exacerbations are defined as 1) an increase in inhaled steroids or oral steroids per se 2) use of antibiotics for a chest infection 3) hospitalization for a chest infection. Patients must be exacerbation free for at least 6 weeks prior to the screening visit. Any clinically significant medical abnormalities (excluding COPD) limiting ability to perform standardized exercise protocol on cycle ergometer will exclude the patient. For example, arthritis. 2. Treatments for COPD and allied conditions: The following medications should NOT be allowed unless they have been stabilized: Ketotifen, omalizumab, Antihistamines (excluding those in 3 below)-at least 5 days prior to screening Other excluded medications: All beta-blocking agents Cardiac anti-arrhythmics Class 1a ( e.g. disopyramide, procainamide, quinidine), Class 3 ( e.g. amiodarone, dofetilide, ibutilide, sotalol), terfenadine, astemizole, mizolastin and any drug with potential to significantly prolong the QT interval Tricyclic antidepressants and monoamine-oxidase inhibitors ( Selective serotonin uptake inhibitors e.g. fluoxetine may only be permitted if the patient's dose has been stable for at least one month prior to screening) 3. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 4. Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. 5. Significant illness within six weeks prior to dosing. 6. A past medical history of, or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome or a prolonged QT-interval at screening. 7. History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug. 8. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 9. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. PLS SEE PROTOCOL
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Primary objective(s) To determine the effect of exercise on maximal heart rate in patients with COPD following therapeutic doses of QAB149 and salmeterol To determine the effect of high-dose nebulized salbutamol on maximal heart rate in patients with COPD following therapeutic doses of QAB149 and salmeterol;Secondary Objective: Secondary objective(s) To evaluate the cardiovascular safety (BP, HR and QTc) of therapeutic doses of QAB149 and salmeterol To evaluate the effect of exercise on change in heart rate from pre-exercise in patients with COPD following therapeutic doses of QAB149 and salmeterol To evaluate the non-cardiovascular safety and tolerability (blood glucose and serum potassium) of therapeutic doses of QAB149 and salmeterol To evaluate the bronchodilator efficacy of therapeutic doses of QAB149 and salmeterol;Primary end point(s): Effect of exercise and high dose salbutamol on maximal heart rate
- Secondary Outcome Measures
Name Time Method