Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 15.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Tiotropium HFA Breath Actuated Inhaler 4.5 mcg/actuation
Product Code: Tiotropium HFA BAI
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: TIOTROPIUM BROMIDE
CA
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent signed and dated by the subject before conducting any study related procedure 2. Male or female subjects 40 -80 years of age, as of the Screening Visit 3. Diagnosis of COPD as defined by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) Guidelines 4. A pre-bronchodilator Peak Inspiratory Flow (PIF) rate= 30 L/ min as measured with the In-CheckTM DIAL training device. 5. A measured post-bronchodilator (ipratropium bromide) FEV1 >30% and =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1 Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject’s last study related visit 2 History or current evidence of a clinically significant or uncontrolled disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neuropsychological, endocrine, gastrointestinal or pulmonary (other than COPD such as asthma, sarcoidosis, non-CF bronchiectasis , cystic fibrosis, bronchopulmonary dysplasia or a diagnosis of alpha 1-antitrypsin deficiency). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the endpoint analysis if the disease/condition exacerbated during the study 3 History of and/or current diagnosis of asthma 4 History of a life-threatening COPD exacerbation 5Thoracotomy with pulmonary resection 6 Current congestive heart failure, history or current evidence of myocardial infarction (within 3 yrs of the Screening Visit [SV]), or history or current evidence of ischemic heart disease, including a diagnosis on screening ECG 7 History or current evidence of clinically significant cardiac arrhythmia, including a diagnosis on screening ECG 8 Presence of angle-closure glaucoma 9 History of malignancy (excluding basal cell carcinoma) within the past 5 years, regardless of the clinical significance or current stability of the disease 10 Known history or any current evidence of renal impairment or urinary retention. This includes abnormal renal function test results at screening 11 Presence of symptomatic prostatic hyperplasia 12 History of silent infections, including positive tests for HIV1, HIV2, Hepatitis B, Hepatitis C, or tuberculosis 13 Occurrence of any upper or lower respiratory infection, including but not limited to the common cold and flu, sinusitis, tonsillitis, pneumonia, bronchitis, or an ear infection (including otitis media and externa) which is not resolved by 14 days prior to randomization 14 Occurrence of a COPD exacerbation which is not resolved by 14 days prior to randomization 15 Subjects who require oxygen therapy and in the investigator’s opinion, will be unable to abstain from the use of oxygen therapy during testing 16 Subjects who have started or stopped an exercise rehabilitation program within 4 weeks of SV 17 Known or suspected hypersensitivity or idiosyncratic reaction to tiotropium, or to any ingredients used in the study medication formulations 18 Severe allergy to milk protein 19 Significant adverse drug reactions, including allergy or hypersensitivity reactions, to atropine or any anticholinergic substance related pharmacologically to atropine 20 Use of any prohibited concomitant medications within the prescribed (per protocol) withdrawal periods prior to SV 21 Treatment with orally administered (excluding orally inhaled) ß-adrenergics 22 Treatment with ß–adrenergic receptor antagonists administered by any route. The single exception is that cardioselective ß1–adrenergic receptor antagonists are permitted provided that subjects have been on a stable dose for at least 1 week prior to SV and subjects are expected to be able to maintain the same dose throughout the study 23 Treatment with drugs commonly recognized to prolong the QTc interval 24 Treatment with any known CYP2D6 or CYP3A4 inhibitors within 30 days prior to SV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess and compare the pharmacokinetics (PK) of Tiotropium delivered via BAI (4.5 mcg or 9.0 mcg), SPIRIVA HandiHaler (18 mcg) and Respimat SMI (5.0 mcg) following repeat dosing for 7 days in subjects with COPD.;Secondary Objective: The secondary objectives of this study are: • To evaluate the efficacy of Tiotropium HFA inhalation aerosol delivered via BAI (4.5 mcg or 9.0 mcg) compared with Tiotropium bromide delivered via SPIRIVA HandiHaler (18 mcg tiotropium) and Respimat SMI (5.0 mcg tiotropium) in subjects with COPD following repeat dosing for 7 days. • To evaluate the safety and tolerability of Tiotropium HFA BAI ;Primary end point(s): Primary Pharmacokinetic Outcome Measures (on Day 7 following 7 days of repeat dosing): • Area under the plasma concentration-time curve on day 7 from time 0 to 24 hours (AUC0-24) for tiotropium • Maximum observed plasma concentration (Cmax) for tiotropium ;Timepoint(s) of evaluation of this end point: Day 7-Day 8, following 7 days repeat dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary Pharmacokinetic: Day 7, following 7 days repeat dosing Other Pharmacokinetic: Day 7 Efficacy: Day 8 (23-24 hours post-dosing on day 7) of each Treatment Period OR Day 7, as detailed above ;Secondary end point(s): Secondary Pharmacokinetic Outcome Measure (on Day 7 following 7 days of repeat dosing): • Area under the plasma concentration-time curve on day 7 from time 0 to the time of the last quantifiable concentration as measured up to 24 hrs (AUC 0-t) for tiotropium • Time at which the maximum plasma concentration was observed (tmax)for tiotropium Other Pharmacokinetic Outcomes: • The cumulative amount of urinary excretion of tiotropium, over 24 hours post-dose on Day 7. • The plasma and urine levels of tiotropium on Day 1, at the start of each dosing period/end of each washout period Efficacy The following efficacy endpoints will be assessed on Day 8 (23-24 hours post-dosing on day 7) of each Treatment Period: • Trough FEV1, defined as the average of the values at 23-24 hours post-Day 7 dose • Trough FVC, defined as the average of the values at 23-24 hours post-Day 7 dose The following efficacy endpoints will be assessed on Day 7 of each Treatment Period: • Time to onset of measured effect (>10% improvement in FEV1 from pre-dose baseline on Day 7) • Time to peak FEV1 • Forced expiratory volume in one second (FEV1) area under the curve for the time period 0 to 24 hours post-dose (FEV1 AUC(0-24h)) • Forced Vital Capacity (FVC) AUC(0-24h) • Peak FEV1 • Peak FVC The following efficacy-related endpoints will be assessed: Rescue medication use within 24 hours prior to study visit assessments and throughout the assessment period on Days 1 and 7 of each Treatment Period. Safety and Tolerability The following endpoints will be measured / recorded to evaluate safety and tolerability. • Serial FEV1 measures during 60 minutes post-dose on Day 1 of each Treatment Period (to assess p | — |
Countries
Germany
Contacts
Public ContactClinical Studies Phase I/II
CRS Clinical Research Services Mannheim GmbH
Outcome results
None listed