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The purpose of this study is to evaluate the dose-response of different doses of CHF 5259 pMDI on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target subject population.
This is a phase II, multicenter, randomized, double-blind, placebo and active controlled dose-ranging 6-arm parallel group study to identify the optimal dose of CHF 5259 pMDI (pressurized metered dose inhaler) with respect to lung function as well as other clinical efficacy and safety outcomes.
After a 2 week run-in period under rescue albuterol and background inhaled corticosteroid (ICS) as needed, patients were randomized to one of the 6 study treatment groups. Following randomization, subjects were assessed after 3 weeks and 6 weeks of study treatment at the study center. A follow-up phone was performed a week after the last visit.
During the study, daily symptoms, rescue and background medication use and compliance with the study drug were recorded in a subject diary. Treatment-Emergent Adverse Events (TEAEs) were assessed and recorded throughout the study. At screening and subsequent visits, subjects underwent physical and vital signs examinations, spirometry measurements, and 12-lead electrocardiogram (ECG). Symptoms and chronic obstructive pulmonary disease (COPD) health status were assessed through validated questionnaires. Routine hematology, blood chemistry, and pregnancy testing were performed before enrollment and at end of study. 24-hour (24-H) digital recording of ECGs (Holter) was performed before and after the first dose and just before the last dose of study treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | CHF 5259 pMDI 6.25 μg, 1 inhalation twice daily (bid); (total daily dose [TDD] of CHF 5259 12.5 μg) |
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| Treatment B | Experimental | CHF 5259 pMDI 12.5 μg, 1 inhalation bid; (TDD of CHF 5259: 25 μg) |
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| Treatment C | Experimental | CHF 5259 pMDI 12.5 μg, 2 inhalations bid; (TDD of CHF 5259: 50 μg) |
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| Treatment D | Experimental | CHF 5259 pMDI 25 μg, 2 inhalations bid; (TDD of CHF 5259: 100 μg) |
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| Treatment E | Placebo Comparator | Placebo, 2 inhalations of CHF 5259 pMDI-matched Placebo bid; |
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| Treatment F | Active Comparator | Tiotropium (TIO) 18 μg, SPIRIVA® HandiHaler®, 2 inhalations once daily (od) of the content of 1 capsule; (TDD of TIO: 18 μg) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CHF 5259 | Drug | Dose Response: Test one of four different doses of CHF 5259 |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6 | Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; | Baseline, Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1 | Change from baseline in FEV1 AUC(0-12h), normalized by time, on Day 1. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Edward Kerwin, MD | Crisor LLC c/o Clinical Research Institute of Southern Oregon, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chiesi Investigational Site | Birmingham | Alabama | 35244 | United States | ||
| Chiesi Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23245604 | Background | Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De Leon FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0. |
| Label | URL |
|---|---|
| From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment A | CHF 5259 pMDI Dose 1, 12.5 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| FG001 | Treatment B | CHF 5259 pMDI Dose 2, 25 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 9, 2018 | Apr 9, 2021 |
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|
| Placebo | Drug | Placebo Control |
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| Tiotropium Bromide 18 µg Inhalation Capsule | Drug | Active Control |
|
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| Baseline, Day 1 |
| Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6 | Change from baseline in FEV1 AUC(0-4h), normalized by time on Day 1 of treatment (Week 0). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 and at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-4h)=Mean FEV1 after inhalation, measured at prespecified times for up to 4-h observation period (0-4h), normalized by time; | Baseline, Day 1, Week 6 |
| Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6 | Change from baseline in FEV1 peak(0-4h) (L) on Day 1 and at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; Peak(0-4h)=Maximum FEV1 between 0 and 4 h. | Baseline, Day 1, Week 6 |
| Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6 | Change from baseline in FVC AUC(0-12h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-12h)=Mean FVC after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; | Baseline, Day 1, Week 6 |
| Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6 | Change from baseline in FVC AUC(0-4h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-4)=Mean FVC after inhalation, measured at prespecified times for up to 4-h observation period (0-4 h), normalized by time; | Baseline, Day 1, Week 6 |
| Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6 | Change from baseline in FVC peak(0-4h) (L) on Day 1 and at the end of treatment at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; Peak(0-4h)=Maximum FEV1 between 0 and 4 h. | Baseline, Day 1, Week 6 |
| Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1 | Time to onset of action is defined as the time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥100 mL. | Day 1 |
| Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1 | Number of patients achieving onset of action was defined as a change from baseline in post-dose FEV1 ≥100 mL on Day 1. These are the patients who contributed to the results, reported as median and 95% CI for 'time to onset of action' presented in Outcome Measure 8, above. | Day 1 |
| Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6 | Change from baseline in FEV1 at treatment visit 3 (Week 3) and treatment visit 4 (Week 6) of treatment. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; | Baseline, Week 3, Week 6 |
| Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6 | Change from baseline in IC at treatment Visit 3 (Week 3) and treatment Visit 4 (Week 6). Spirometry was used to measure IC and was performed according to internationally accepted standards. Definitions: Baseline: value of the measurement recorded at 45 mins pre-dose at Visit 2 (Week 0); IC=Inspiratory capacity; | Baseline, Week 3, Week 6 |
| Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6 | Number of subjects achieving TDI focal score ≥1, at treatment visit 3 (Week 3) and at treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement); total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index; | Baseline, Week 3, Week 6 |
| Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6 | Transitional Dyspnea Index (TDI) focal score at treatment visit 3 (Week 3) and treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement), with a total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index; | Baseline, Week 3, Week 6 |
| Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period | Evaluate the number of rescue medication-free days compared with baseline. Results are shown as percentage (%) of rescue medication-free days; an increased value indicates improvement from baseline. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3, Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0). | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
| Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period | Evaluate the change from baseline in average use of rescue medication (number of puffs/day) during the inter-visit periods and the entire treatment period. Results are shown as number of puffs/day; a decrease (implies improvement) from baseline in average use of rescue medication. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3 (Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0); | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
| Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period | Change from baseline in average EXACT-Respiratory Symptom (E-RS) total score during inter-visit periods and the entire treatment period E-RS in COPD uses 11 respiratory symptom items from the 14-item EXAcerbations of COPD tool (EXACT). E-RS total score quantifies respiratory symptom severity on a scale ranging from 0 to 40. Higher E-RS total scores indicate more severe symptoms and a declining total score indicates health improvement. E-RS questionnaire was completed by the patient each evening (e-diary). Definitions: For details on baseline, inter-visit periods, and the entire treatment period, please refer to outcome measure #15. | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
| Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | Vital signs -- Systolic blood pressure (SBP), Diastolic blood pressure (DBP) were measured at prespecified times, using a 12-Lead single ECGs were recorded at all study visits (pre-dose at V1 (Week -2) and V3 (Week 3), as well as at pre-dose and 1.5 hours post-dose at Visit 2 (Week 0) and Visit 4 (Week 6). Results are shown by treatment group, as change from baseline (in mmHg) for representative timepoints. Definitions: Baseline=Values recorded pre-dose (Visit 2, Week 0); Day 1=Day of the first dose of randomized study drug (Visit 2, Week 0); | Baseline, Day 1, Week 6 |
| Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR) | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Heart rate (HR) Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5m, +55m, and at +2.5 h. | Baseline, Day 1, Week 6 |
| Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - PR Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Baseline, Day 1, Week 6 |
| Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - QRS Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Baseline, Day 1, Week 6 |
| Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF) | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Fridericia-corrected QT interval (QTcF). Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Baseline, Day 1, Week 6 |
| 24-hour Holter ECG - Prolonged QTcF - Male Subjects | 24-hour Holter ECG - Prolonged QTcF - Male subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Baseline, Day 1, Week 6 |
| 24-hour Holter ECG - Prolonged QTcF - Female Subjects | 24-hour Holter ECG - Prolonged QTcF - Female subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Baseline, Day 1, Week 6 |
| 24-hour Holter ECG - Prolonged QTcF - Change From Baseline | 24-hour Holter ECG - Prolonged QTcF - Change from baseline. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. Results are presented as the number of subjects who had a change from baseline in QTcF of: > 30 msec, > 60 msec, and no prolongation (by > 30 msec or > 60 msec). | Baseline, Day 1, Week 6 |
| Dothan |
| Alabama |
| 36305 |
| United States |
| Chiesi Investigational Site | Montgomery | Alabama | 36106 | United States |
| Chiesi Investigational Site | Flagstaff | Arizona | 86001 | United States |
| Chiesi Investigational Site | Glendale | Arizona | 85306 | United States |
| Chiesi Investigational Site | Phoenix | Arizona | 85006 | United States |
| Chiesi Investigational Site | Phoenix | Arizona | 85014 | United States |
| Chiesi Investigational Site | Phoenix | Arizona | 85018 | United States |
| Chiesi Investigational Site | Surprise | Arizona | 85374 | United States |
| Chiesi Investigational Site | Tempe | Arizona | 85283 | United States |
| Chiesi Investigational Site | Tucson | Arizona | 85710 | United States |
| Chiesi Investigational Site | Anaheim | California | 92801 | United States |
| Chiesi Investigational Site | Escondido | California | 92025 | United States |
| Chiesi Investigational Site | Fullerton | California | 92835 | United States |
| Clinical Trials Research | Lincoln | California | 95648 | United States |
| Chiesi Investigational Site | Long Beach | California | 90806 | United States |
| Chiesi Investigational Site | Los Angeles | California | 90017 | United States |
| Chiesi Investigational Site | Los Angeles | California | 90036 | United States |
| Chiesi Investigational Site | Los Angeles | California | 90048 | United States |
| Chiesi Investigational Site | Newport Beach | California | 92663 | United States |
| Chiesi Investigational Site | San Diego | California | 92120 | United States |
| Chiesi Investigational Site | Tustin | California | 92780 | United States |
| Chiesi Investigational Site | Westminster | California | 92683 | United States |
| Chiesi Investigational Site | Boulder | Colorado | 80301 | United States |
| Chiesi Investigational Site | Centennial | Colorado | 80112 | United States |
| Chiesi Investigational Site | Denver | Colorado | 80230 | United States |
| Chiesi Investigational Site | Lafayette | Colorado | 80026 | United States |
| Chiesi Investigational Site | Brandon | Florida | 33511 | United States |
| Chiesi Investigational Site | Clearwater | Florida | 33765 | United States |
| Chiesi Investigational Site | Daytona Beach | Florida | 32117 | United States |
| Chiesi Investigational Site | Edgewater | Florida | 32132 | United States |
| Chiesi Investigational Site | Hialeah | Florida | 33012 | United States |
| Chiesi Investigational Site | Kissimmee | Florida | 34741 | United States |
| Chiesi Investigational Site | Miami | Florida | 33144 | United States |
| Chiesi Investigational Site | Miami | Florida | 33165 | United States |
| Chiesi Investigational Site | Miami | Florida | 33176 | United States |
| Chiesi Investigational Site | Miami | Florida | 33186 | United States |
| Chiesi Investigational Site | Orlando | Florida | 32825 | United States |
| Chiesi Investigational Site | Panama City | Florida | 32405 | United States |
| Chiesi Investigational Site | Blue Ridge | Georgia | 30513 | United States |
| Chiesi Investigational Site | Dacula | Georgia | 30019 | United States |
| Chiesi Investigational Site | Duluth | Georgia | 30096 | United States |
| Chiesi Investigational Site | Lawrenceville | Georgia | 30046 | United States |
| Chiesi Investigational Site | Marietta | Georgia | 30060 | United States |
| Chiesi Investigational Site | Savannah | Georgia | 31405 | United States |
| Chiesi Investigational Site | Chicago | Illinois | 60607 | United States |
| Chiesi Investigational Site | Evansville | Indiana | 47714 | United States |
| Chiesi Investigational Site | Valparaiso | Indiana | 46383 | United States |
| Chiesi Investigational Site | Louisville | Kentucky | 40215 | United States |
| Chiesi Investigational Site | Louisville | Kentucky | 40218 | United States |
| Chiesi Investigational Site | Crowley | Louisiana | 70526 | United States |
| Chiesi Investigational Site | Lake Charles | Louisiana | 70601 | United States |
| Chiesi Investigational Site | Lutherville | Maryland | 21093 | United States |
| Chiesi Investigational Site | Fall River | Massachusetts | 02720 | United States |
| Chiesi Investigational Site | Fall River | Massachusetts | 02721 | United States |
| Chiesi Investigational Site | Ann Arbor | Michigan | 48106 | United States |
| Chiesi Investigational Site | Farmington Hills | Michigan | 48336 | United States |
| Chiesi Investigational Site | Minneapolis | Minnesota | 55402 | United States |
| Chiesi Investigational Site | Saint Charles | Missouri | 63301 | United States |
| Chiesi Investigational Site | St Louis | Missouri | 63141 | United States |
| Chiesi Investigational Site | Missoula | Montana | 59808 | United States |
| Chiesi Investigational Site | Omaha | Nebraska | 68114 | United States |
| Chiesi Investigational Site | Las Vegas | Nevada | 89119 | United States |
| Chiesi Investigational Site | Summit | New Jersey | 07901 | United States |
| Chiesi Investigational Site | Albuquerque | New Mexico | 87108 | United States |
| Chiesi Investigational Site | The Bronx | New York | 10455 | United States |
| Chiesi Investigational Site | Charlotte | North Carolina | 28207 | United States |
| Chiesi Investigational Site | Gastonia | North Carolina | 28054 | United States |
| Chiesi Investigational Site | Hendersonville | North Carolina | 28739 | United States |
| Chiesi Investigational Site | Mooresville | North Carolina | 28117 | United States |
| Chiesi Investigational Site | Raleigh | North Carolina | 27607 | United States |
| Chiesi Investigational Site | Shelby | North Carolina | 28150 | United States |
| Chiesi Investigational Site | Wilmington | North Carolina | 28401 | United States |
| Chiesi Investigational Site | Winston-Salem | North Carolina | 27103 | United States |
| Chiesi Investigational Site | Cincinnati | Ohio | 45242 | United States |
| Chiesi Investigational Site | Columbus | Ohio | 43213 | United States |
| Chiesi Investigational Site | Columbus | Ohio | 43215 | United States |
| Clinical Research Solutions | Dayton | Ohio | 45409 | United States |
| Chiesi Investigational Site | Grove City | Ohio | 43123 | United States |
| Chiesi Investigational Site | Edmond | Oklahoma | 73034 | United States |
| Chiesi Investigational Site | Oklahoma City | Oklahoma | 73103 | United States |
| Chiesi Investigational Site | Medford | Oregon | 97504 | United States |
| Chiesi Investigational Site | Portland | Oregon | 97202 | United States |
| Chiesi Investigational Site | Philadelphia | Pennsylvania | 19140 | United States |
| Chiesi Investigational Site | East Providence | Rhode Island | 02914 | United States |
| Chiesi Investigational Site | Anderson | South Carolina | 29621 | United States |
| Chiesi Investigational Site | Charleston | South Carolina | 29406 | United States |
| Chiesi Investigational Site | Easley | South Carolina | 29640 | United States |
| Chiesi Investigational Site | Fort Mill | South Carolina | 29707 | United States |
| Chiesi Investigational Site | Gaffney | South Carolina | 29340 | United States |
| Chiesi Investigational Site | Greenville | South Carolina | 29615 | United States |
| Chiesi Investigational Site | Mt. Pleasant | South Carolina | 29464 | United States |
| Chiesi Investigational Site | Orangeburg | South Carolina | 29118 | United States |
| Chiesi Investigational Site | Rock Hill | South Carolina | 29732 | United States |
| Chiesi Investigational Site | Seneca | South Carolina | 29678 | United States |
| Chiesi Investigational Site | Spartanburg | South Carolina | 29303 | United States |
| Chiesi Investigational Site | Union | South Carolina | 29379 | United States |
| Chiesi Investigational Site | Rapid City | South Dakota | 57702 | United States |
| Chiesi Investigational Site | Franklin | Tennessee | 37067 | United States |
| Chiesi Investigational Site | Jackson | Tennessee | 38305 | United States |
| Chiesi Investigational Site | Knoxville | Tennessee | 37909 | United States |
| Chiesi Investigational Site | Tullahoma | Tennessee | 37388 | United States |
| Chiesi Investigational Site | Boerne | Texas | 78006 | United States |
| Chiesi Investigational Site | Cypress | Texas | 77429 | United States |
| Chiesi Investigational Site | New Braunfels | Texas | 78130 | United States |
| Chiesi Investigational Site | Sherman | Texas | 75092 | United States |
| Chiesi Investigational Site | Tomball | Texas | 77375 | United States |
| Chiesi Investigational Site | South Burlington | Vermont | 05403 | United States |
| Chiesi Investigational Site | Richmond | Virginia | 23225 | United States |
| Chiesi Investigational Site | Everett | Washington | 98208 | United States |
| Chiesi Investigational Site | Richland | Washington | 99352 | United States |
| Chiesi Investigational Site | Tacoma | Washington | 98405 | United States |
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| Glycopyrronium bromide | View source |
| American Thoracic Society: Baseline Dyspnea Index (BDI) \& Transition Dyspnea Index (TDI). | View source |
| American Thoracic Society: COPD Assessment Test (CAT). | View source |
| FG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| FG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| FG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| FG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
| COMPLETED |
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| NOT COMPLETED |
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Eligible patients male or female, aged ≥ 40 years with a diagnosis of COPD at least 12 months before the screening visit, who were current smokers or ex-smokers who had quit smoking at least 6 months prior to the screening visit, with a smoking history of at least 10 pack-years. Study inclusion and exclusion criteria are presented in the study protocol section.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment A | CHF 5259 pMDI, 6.25 μg, 1 inhalation bid; 12.5 μg TDD CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259 |
| BG001 | Treatment B | CHF 5259 pMDI 12.5 μg, 1 inhalation bid; 25 μg TDD CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259 |
| BG002 | Treatment C | CHF 5259 pMDI 12.5 μg, 2 inhalations bid; 50 μg TDD CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259 |
| BG003 | Treatment D | CHF 5259 pMDI 25 μg, 2 inhalations bid; 100 μg TDD CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259 |
| BG004 | Treatment E | Placebo 2 inhalations of CHF 5259 pMDI-matched Placebo bid Placebo: Placebo Control |
| BG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 μg, SPIRIVA® HandiHaler®, 2 inhalations od of the content of 1 capsule; 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Time since first diagnosis of COPD | Median | Full Range | months |
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| Age at first diagnosis of COPD | Mean | Standard Deviation | years |
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| COPD medication category at study entry | Count of Participants | Participants |
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| Smoking habits | Count of Participants | Participants |
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| Duration of smoking | Mean | Standard Deviation | years |
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| Number of pack-years | A pack-year is a term used to describe the approximate number of cigarettes a person has smoked over time. 1 One pack-year equals 20 manufactured cigarettes smoked per day for one year. | Median | Full Range | pack-years |
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| FEV1 (L) at baseline | Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath during the first second (FEV1). | Mean | Standard Deviation | litres |
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| FVC at baseline | Forced vital capacity (FVC) is the maximal volume of gas that can be exhaled from full inhalation by exhaling as forcefully and rapidly as possible. | Mean | Standard Deviation | litres |
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| IC at baseline | Inspiratory capacity (IC) is the amount of air taken in during a deep breath, without hesitation, after a normal, relaxed expiration. IC is decreased in obstructive lung diseases. | Mean | Standard Deviation | litres |
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| BDI focal scores at randomization | Baseline Dyspnea Index (BDI): a validated, interviewer-administered rating of severity of dyspnea. It provides a multidimensional measurement of dyspnea evoked in activities of daily living, in symptomatic individuals during the last 2 weeks. BDI consists of 24 items (3 domains: Functional Impairment, Magnitude of Task, and Magnitude of Effort), each rated on a 5-point scale from 0 (very severe impairment) to 4 (no impairment), with a total score ranging from 0-12. Only patients with a BDI focal score ≤10 at screening, and at randomization were eligible for enrolment into the current trial. | Mean | Standard Deviation | scores on a scale |
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| CAT total score at randomization | COPD Assessment Test (CAT) is a patient-completed validated questionnaire. It measures the global impact of COPD on a patient's life in an objective way and monitors changes over time. CAT consists of eight items scored on a scale of 1 to 5, with a total score range of 0-40; a higher score denotes a more severe impact of COPD on a patient's life. Only patients with a CAT score ≥10 at screening and at randomisation were eligible for enrolment into the current trial. | Mean | Standard Deviation | scores on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6 | Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Week 6 |
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| Secondary | Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1 | Change from baseline in FEV1 AUC(0-12h), normalized by time, on Day 1. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1 |
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| Secondary | Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6 | Change from baseline in FEV1 AUC(0-4h), normalized by time on Day 1 of treatment (Week 0). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 and at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-4h)=Mean FEV1 after inhalation, measured at prespecified times for up to 4-h observation period (0-4h), normalized by time; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6 | Change from baseline in FEV1 peak(0-4h) (L) on Day 1 and at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; Peak(0-4h)=Maximum FEV1 between 0 and 4 h. | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6 | Change from baseline in FVC AUC(0-12h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-12h)=Mean FVC after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6 | Change from baseline in FVC AUC(0-4h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-4)=Mean FVC after inhalation, measured at prespecified times for up to 4-h observation period (0-4 h), normalized by time; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6 | Change from baseline in FVC peak(0-4h) (L) on Day 1 and at the end of treatment at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; Peak(0-4h)=Maximum FEV1 between 0 and 4 h. | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Day 1, Week 6 |
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| Secondary | Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1 | Time to onset of action is defined as the time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥100 mL. | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Mean | 95% Confidence Interval | minutes | Day 1 |
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| Secondary | Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1 | Number of patients achieving onset of action was defined as a change from baseline in post-dose FEV1 ≥100 mL on Day 1. These are the patients who contributed to the results, reported as median and 95% CI for 'time to onset of action' presented in Outcome Measure 8, above. | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Count of Participants | Participants | Day 1 |
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| Secondary | Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6 | Change from baseline in FEV1 at treatment visit 3 (Week 3) and treatment visit 4 (Week 6) of treatment. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; | Intention to treat All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Week 3, Week 6 |
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| Secondary | Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6 | Change from baseline in IC at treatment Visit 3 (Week 3) and treatment Visit 4 (Week 6). Spirometry was used to measure IC and was performed according to internationally accepted standards. Definitions: Baseline: value of the measurement recorded at 45 mins pre-dose at Visit 2 (Week 0); IC=Inspiratory capacity; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Litres | Baseline, Week 3, Week 6 |
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| Secondary | Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6 | Number of subjects achieving TDI focal score ≥1, at treatment visit 3 (Week 3) and at treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement); total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Count of Participants | Participants | Baseline, Week 3, Week 6 |
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| Secondary | Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6 | Transitional Dyspnea Index (TDI) focal score at treatment visit 3 (Week 3) and treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement), with a total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index; | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Week 3, Week 6 |
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| Secondary | Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period | Evaluate the number of rescue medication-free days compared with baseline. Results are shown as percentage (%) of rescue medication-free days; an increased value indicates improvement from baseline. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3, Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0). | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | % of of rescue medication-free days | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
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| Secondary | Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period | Evaluate the change from baseline in average use of rescue medication (number of puffs/day) during the inter-visit periods and the entire treatment period. Results are shown as number of puffs/day; a decrease (implies improvement) from baseline in average use of rescue medication. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3 (Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0); | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | Number of puffs/day | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
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| Secondary | Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period | Change from baseline in average EXACT-Respiratory Symptom (E-RS) total score during inter-visit periods and the entire treatment period E-RS in COPD uses 11 respiratory symptom items from the 14-item EXAcerbations of COPD tool (EXACT). E-RS total score quantifies respiratory symptom severity on a scale ranging from 0 to 40. Higher E-RS total scores indicate more severe symptoms and a declining total score indicates health improvement. E-RS questionnaire was completed by the patient each evening (e-diary). Definitions: For details on baseline, inter-visit periods, and the entire treatment period, please refer to outcome measure #15. | Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables). | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period |
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| Secondary | Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | Vital signs -- Systolic blood pressure (SBP), Diastolic blood pressure (DBP) were measured at prespecified times, using a 12-Lead single ECGs were recorded at all study visits (pre-dose at V1 (Week -2) and V3 (Week 3), as well as at pre-dose and 1.5 hours post-dose at Visit 2 (Week 0) and Visit 4 (Week 6). Results are shown by treatment group, as change from baseline (in mmHg) for representative timepoints. Definitions: Baseline=Values recorded pre-dose (Visit 2, Week 0); Day 1=Day of the first dose of randomized study drug (Visit 2, Week 0); | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Mean | Full Range | mmHg | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR) | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Heart rate (HR) Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5m, +55m, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Mean | Full Range | bpm | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - PR Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Mean | Full Range | msec | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - QRS Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Mean | Full Range | msec | Baseline, Day 1, Week 6 |
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| Secondary | Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF) | Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Fridericia-corrected QT interval (QTcF). Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Mean | Full Range | msec | Baseline, Day 1, Week 6 |
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| Secondary | 24-hour Holter ECG - Prolonged QTcF - Male Subjects | 24-hour Holter ECG - Prolonged QTcF - Male subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline, Day 1, Week 6 |
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| Secondary | 24-hour Holter ECG - Prolonged QTcF - Female Subjects | 24-hour Holter ECG - Prolonged QTcF - Female subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline, Day 1, Week 6 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 24-hour Holter ECG - Prolonged QTcF - Change From Baseline | 24-hour Holter ECG - Prolonged QTcF - Change from baseline. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. Results are presented as the number of subjects who had a change from baseline in QTcF of: > 30 msec, > 60 msec, and no prolongation (by > 30 msec or > 60 msec). | Safety population: All randomized patients who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline, Day 1, Week 6 |
|
From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | CHF 5259 pMDI Dose 1, 12.5 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 | 0 | 121 | 2 | 121 | 16 | 121 |
| EG001 | Treatment B | CHF 5259 pMDI Dose 2, 25 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 | 0 | 123 | 5 | 123 | 14 | 123 |
| EG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 | 0 | 121 | 1 | 121 | 8 | 121 |
| EG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 | 0 | 123 | 1 | 123 | 15 | 123 |
| EG004 | Treatment E | Placebo Control Placebo: Placebo Control | 0 | 121 | 1 | 121 | 11 | 121 |
| EG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule | 0 | 123 | 1 | 123 | 9 | 123 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Prostate cancer stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
Chiesi can publish and/or present any results of this study at scientific meetings, and to submit the clinical trial data to national and international Regulatory Authorities. Chiesi reserves the right to use such data for industrial purposes. Investigators will inform Chiesi before using the results of the study for publication or presentation, and agree to provide the Sponsor with a copy of the proposed presentation. Data from individual study sites must not be published separately.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Transparency | Chiesi Farmaceutici S.p.A. | + 39 0521 2791 | clinicaltrials_info@chiesi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 20, 2018 | Apr 9, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| D001239 | Inhalation |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D015656 | Respiratory Mechanics |
| D012119 | Respiration |
| D012143 | Respiratory Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
Not provided
Not provided
| 65-84 years |
|
| > 85 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Inhaled ICS and LABA (free combination) |
|
| Inhaled ICS/LABA (fixed combination) |
|
| Inhaled ICS and LAMA |
|
| Inhaled ICS+LABA+LAMA (free or fixed combination) |
|
| Inhaled LABA/LAMA (fixed combination) |
|
| Ex-smoker |
|
| Comparison treatment groups were: Treatment B (CHF 5259 pMDI 25 μg TDD) versus Treatment E (Placebo). Statistical analysis for was performed as described for the statistical analysis 1 for this outcome measure. Adjusted for multiplicity based on the parametric simulation method by Edwards and Berry. | Mixed Models Analysis | <0.001 | Mean Difference (Final Values) | 0.116 | 2-Sided | 95 | 0.051 | 0.181 | Superiority |
| Comparison treatment groups were: Treatment C (CHF 5259 pMDI 50 μg TDD) versus Treatment E (Placebo). Statistical analysis for was performed as described for the statistical analysis 1 for this outcome measure. Adjusted for multiplicity based on the parametric simulation method by Edwards and Berry. | Mixed Models Analysis | <0.001 | Mean Difference (Final Values) | 0.151 | 2-Sided | 95 | 0.086 | 0.216 | Superiority |
| Comparison treatment groups were: Treatment D (CHF 5259 pMDI 100 μg TDD) versus Treatment E (Placebo). Statistical analysis for was performed as described for the statistical analysis 1 for this outcome measure. Adjusted for multiplicity based on the parametric simulation method by Edwards and Berry. | Mixed Models Analysis | <0.001 | Mean Difference (Final Values) | 0.145 | 2-Sided | 95 | 0.081 | 0.209 | Superiority |
| Comparison treatment groups were: Treatment F (Tiotropium 18 μg TDD) versus Treatment E (Placebo). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | <0.001 | Mean Difference (Final Values) | 0.211 | 2-Sided | 95 | 0.159 | 0.263 | Superiority |
| Comparison treatment groups were: Treatment B (CHF 5259 pMDI 25 μg TDD) versus Treatment A (CHF 5259 pMDI 12.5 μg TDD). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.066 | Mean Difference (Final Values) | 0.048 | 2-Sided | 95 | -0.003 | 0.100 | Superiority |
| Comparison treatment groups were: Treatment C (CHF 5259 pMDI 50 μg TDD) versus Treatment A (CHF 5259 pMDI 12.5 μg TDD). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.002 | Mean Difference (Final Values) | 0.083 | 2-Sided | 95 | 0.031 | 0.135 | Superiority |
| Comparison treatment groups were: Treatment D (CHF 5259 pMDI 100 μg TDD) versus Treatment A (CHF 5259 pMDI 12.5 μg TDD). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.003 | Mean Difference (Final Values) | 0.077 | 2-Sided | 95 | 0.026 | 0.128 | Superiority |
| Comparison treatment groups were: Treatment C (CHF 5259 pMDI 50 μg TDD) versus Treatment B (CHF 5259 pMDI 25 μg TDD. Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.189 | Mean Difference (Final Values) | 0.035 | 2-Sided | 95 | -0.017 | 0.087 | Superiority |
| Comparison treatment groups were: Treatment D (CHF 5259 pMDI 100 μg TDD) versus Treatment B (CHF 5259 pMDI 25 μg TDD). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.273 | Mean Difference (Final Values) | 0.029 | 2-Sided | 95 | -0.023 | 0.080 | Superiority |
| Comparison treatment groups were: Treatment D (CHF 5259 pMDI 100 μg TDD) versus Treatment C (CHF 5259 pMDI 50 μg TDD). Analyzed using a linear mixed model for repeated measures (MMRM) including treatment, visit, treatment by visit interaction, US regions (Midwest, Northeast, South and West)" and smoking status at screening as fixed effects, and the baseline value and baseline by visit interaction as covariates. | Mixed Models Analysis | 0.813 | Mean Difference (Final Values) | -0.006 | 2-Sided | 95 | -0.058 | 0.045 | Superiority |
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| Treatment D |
CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
CHF 5259 pMDI Dose 2, 25 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
CHF 5259 pMDI Dose 2, 25 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| Treatment B |
CHF 5259 pMDI Dose 2, 25 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG002 | Treatment C | CHF 5259 pMDI Dose 3, 50 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| Treatment D |
CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| Treatment D |
CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
|
|
| OG003 | Treatment D | CHF 5259 pMDI Dose 4, 100 μg TDD CHF 5259 Dose Response: Test one of four different doses of CHF 5259 |
| OG004 | Treatment E | Placebo Control Placebo: Placebo Control |
| OG005 | Treatment F | Tiotropium Bromide inhalation powder, 18 µg TDD Tiotropium Bromide Active Control, 18 µg Inhalation Capsule |
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| Actual value > 480 msec |
|
| Actual value > 500 msec |
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| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
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| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 480 msec |
|
| Actual value > 500 msec |
|
| No prolongation (> 450 msec or > 480 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Actual value > 500 msec |
|
| No prolongation (> 470 msec or > 500 msec) |
|
| Change from baseline: > 60 msec |
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| No change from baseline (> 30 msec or > 60 msec) |
|
| Change from baseline: > 60 msec |
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| No change from baseline (> 30 msec or > 60 msec) |
|
| Change from baseline: > 60 msec |
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| No change from baseline (> 30 msec or > 60 msec) |
|
| Change from baseline: > 60 msec |
|
| No change from baseline (> 30 msec or > 60 msec) |
|
| Change from baseline: > 60 msec |
|
| No change from baseline (> 30 msec or > 60 msec) |
|
| Change from baseline: > 60 msec |
|
| No change from baseline (> 30 msec or > 60 msec) |
|