Chronic Obstructive Pulmonary Disease MedDRA version: 21.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Spiolto® Respimat®
Product Name: Spiolto® Respimat®
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Tiotropiumbromid
CAS Number: 411207-31-3
Other descriptive name: TIOTROPI
Sponsors
Fraunhofer Society
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent. 2. Male and female subjects, aged = 40 years. Women will be considered for inclusion if they are: Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing. Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit). Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the first dose of study medication until at least 72 hours after treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap). 3. Subjects with stable COPD according to the current GOLD guidelines (GOLD 2018). 4. Subjects with airflow limitation indicated by a post-bronchodilator FEV1 135% predicted as measured at Visit 1, before intake of salbutamol. 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 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1.Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, lung function or ECG at screening visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject’s ability to participate in the study. 2.Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease (including but not confined to aneurysm, hypokalemia, decompensated heart failure or hypertrophic obstructive cardiomyopathy), malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease (including but not confined to thyrotoxicosis) or pulmonary disease other than COPD (including but not confined to tuberculosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, interstitial lung disease or lung fibrosis). 3.Use of other investigational drug (approved or unapproved) at the time of enrolment, or within 30 days or 5 half-lives prior to Visit 1, whichever is longer. 4.History of drug or alcohol abuse. 5.Risk of non-compliance with study procedures. 6.Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study. 7.History of an acute respiratory infection four weeks prior to Visit 1 and between Visit 1 and 3. These patients will not be eligible, but will be permitted to rescreened 4 weeks after the resolution of the respiratory tract infection. 8.Subjects with conditions contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: •anticholinergics •long and short acting beta-2 agonists •sympathomimetic amines 9.Subjects with a history of long QT syndrome or whose QTcF (Fridericia method) measured at Visit 1 is prolonged (>450 ms for males and >470 ms for females). These subjects should not be re-screened. 10.Subjects who have clinically significant cardiovascular abnormalities, which could interfere with the assessment of the study treatment (such as but not limited to cardiac arrhythmias, heart failure with left ventricular ejection fraction 160 mmHg and/or mean sitting diastolic blood pressure > 90 mmHg at Visit 1. These subjects will be permitted to be re-screened after initiation or intensification of an antihypertensive therapy and achieving a controlled disease status. 15.History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 16.Subjects with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or severe renal impairment (GFR = 50 mL/min/1.73 m2) inclu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the change from baseline in left ventricular end-diastolic volume (LVEDV) index evaluated by MRI in mL/m2 after single dose administration of Spiolto® Respimat® versus nebulized saline in hyperinflated COPD patients.;Secondary Objective: To determine the change from baseline in •LVEDV evaluated by MRI in mL/m2 after multiple dose administration of Spiolto® Respimat® compared with single dose administration. •muscle sympathetic nerve activity evaluated by microneurography as bursts/ 100 heart beats after single dose administration of Spiolto® Respimat® versus nebulized saline. •residual volume and other lung function parameters such as FEV1, FVC, IC, TLC, specific airway resistance, FRC and forced expiratory flows after single dose of Spiolto® Respimat® versus nebulized saline and after multiple dose administration of Spiolto® Respimat® compared with single dose administration •exhaled particle numbers per volume after single dose of Spiolto® Respimat® versus nebulized saline. •exhaled particle numbers per volume after multiple dose administration of Spiolto® Respimat® compared with single dose administration. ;Primary end point(s): To determine the change from baseline in left ventricular end-diastolic volume index evaluated by MRI in mL/m2 after single dose administration of Spiolto® Respimat® versus nebulized saline in hyperinflated COPD patients.;Timepoint(s) of evaluation of this end point: Visit number 2, 3, 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the change from baseline in • LVEDV evaluated by MRI in mL/m2 after multiple dose administration of Spiolto® Respimat® compared with single dose administration. • muscle sympathetic nerve activity evaluated by microneurography as bursts/ 100 heart beats after single dose administration of Spiolto® Respimat® versus nebulized saline. • residual volume and other lung function parameters such as FEV1, FVC, IC, TLC, specific airway resistance, FRC and forced expiratory flows after single dose of Spiolto® Respimat® versus nebulized saline and after multiple dose administration of Spiolto® Respimat® compared with single dose administration • exhaled particle numbers per volume after single dose of Spiolto® Respimat® versus nebulized saline. • exhaled particle numbers per volume after multiple dose administration of Spiolto® Respimat® compared with single dose administration.;Timepoint(s) of evaluation of this end point: Visit number 2, 3, 4, 5 | — |
Countries
Germany
Contacts
Public ContactJens Hohlfeld
Fraunhofer-Institute for Toxicology and Experimental Medicine ITEM
Outcome results
None listed