Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01610037
First received: May 30, 2012
Last updated: May 9, 2016
Last verified: May 2016
Results First Received: February 1, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Chronic Obstructive Pulmonary Disease (COPD)
Interventions: Drug: QVA149
Drug: Tiotropium
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 2064 patients were screened, of whom 1216 patients were randomized to QVA149 110/50 µg o.d., tiotropium 18 µg o.d., or placebo. Of the 1216, one patient was randomized but not treated.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One patient of the 1216 was randomized but did not receive treatment

Reporting Groups
  Description
QVA149 110/50 µg capsules for inhalation, o.d
Tiotropium 18 μg capsules for inhalation, o.d
Placebo To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Participant Flow for 2 periods

Period 1:   All Patients
    QVA149     Tiotropium     Placebo  
STARTED     407     405     404  
Randomized Set (RAN)     407     405     404  
Full Analysis Set (FAS)     407     405     403  
COMPLETED     348     354     320  
NOT COMPLETED     59     51     84  
Adverse Event                 27                 22                 26  
Withdrawal by Subject                 12                 10                 20  
Unsatisfactory therapeutic effect                 9                 8                 27  
Death                 4                 2                 1  
Protocol deviation                 4                 3                 3  
Abnormal laboratory value                 1                 1                 0  
Administrative problems                 1                 4                 4  
Lost to Follow-up                 1                 0                 0  
Abnormal test procedure result(s)                 0                 1                 3  

Period 2:   Treatment and Follow up Period
    QVA149     Tiotropium     Placebo  
STARTED     407     405     404  
COMPLETED     382     377     378  
NOT COMPLETED     25     28     26  
Subject withdrew consent                 13                 14                 16  
Death                 10                 5                 4  
Administrative problems                 1                 3                 2  
Lost to Follow-up                 1                 6                 4  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The RAN included all randomized patients regardless of whether or not they actually received study medication.

Reporting Groups
  Description
QVA149 110/50 µg capsules for inhalation, o.d
Tiotropium 18 μg capsules for inhalation, o.d
Placebo To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d
Total Total of all reporting groups

Baseline Measures
    QVA149     Tiotropium     Placebo     Total  
Number of Participants  
[units: participants]
  407     405     404     1216  
Age  
[units: Years]
Mean (Standard Deviation)
  64.6  (7.89)     64.1  (8.57)     64.9  (7.95)     64.5  (8.14)  
Gender  
[units: Participants]
       
Female     119     105     94     318  
Male     288     300     310     898  



  Outcome Measures
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1.  Primary:   Number of Patients With Serious Adverse Events   [ Time Frame: Week 52 ]

2.  Secondary:   Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events.   [ Time Frame: 52 weeks ]

3.  Secondary:   Post-hoc Analysis: Percentage of Patients With Composite Endpoint of Cardiovascular Death and MACE   [ Time Frame: 52 weeks ]

4.  Secondary:   Change From Baseline in Pre-Dose Forced Expiratory Volume Over in Second (FEV1)   [ Time Frame: Day 22, 43, 85, 183, 274 and 364 ]

5.  Secondary:   Change From Baseline in Health Status as Measured by St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)   [ Time Frame: Measurment at day 364 ]

6.  Secondary:   Change From Baseline in Daily, Morning and Evening Symptom Scores   [ Time Frame: 52 weeks ]

7.  Secondary:   Change From Baseline in Percentage of Nights With ‘no Nighttime Awakenings   [ Time Frame: 52 weeks ]

8.  Secondary:   Change From Baseline in Percentage of no Daytime Symptoms   [ Time Frame: 52 weeks ]

9.  Secondary:   Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities.   [ Time Frame: 52 weeks ]

10.  Secondary:   Change From Baseline in 1 Hour Post-dose Forced Vital Capacity (FVC) Measurements   [ Time Frame: Day 1, 22, 43, 85, 183, 274 and 364 ]

11.  Secondary:   Time to Premature Discontinuation   [ Time Frame: Time varied from 5 - 407 days ]

12.  Secondary:   Change From Baseline in 1 Hour Post-dose FEV1 Measurements   [ Time Frame: Day 1, 22, 43, 85, 183, 274 and 364 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01610037     History of Changes
Other Study ID Numbers: CQVA149A2339
2012-002057-38 ( EudraCT Number )
Study First Received: May 30, 2012
Results First Received: February 1, 2016
Last Updated: May 9, 2016
Health Authority: Argentina: Administracion Nacional de Alimentos, Medicamentos y Tecnologia Medica (ANMAT)
Croatia: Ministry of Health
Dominican Republic: Consejo Nacional de Bioetica en Salud (CONABIOS)
Estonia: State Agency of Medicine
Hungary: Directorate General of National Institute of Pharmacy/ National Institute for Quality and Organisational Development in Healthcare and Medicines
India: Drugs Controller General of India
Ireland: Irish Medicines Board (IMB)
Israel: Israeli Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Latvia: State Agency of Medicines of Latvia
Mexico: Ministry of Health
Panama: Comite Nacional de Bioetica de la Investigacion con sede en Instituto Conmemorativo Gorgas de Estudios de la Salud (Ministry of Health)
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Serbia: Medicines and Medical Devices Agency of Serbia
Slovenia: Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices
Turkey: Ministry of Health - Turkish Medicines and Medical Devices Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Instituto Nacional de Higiene Rafael Rangel