Safety of Indacaterol in Patients (≥ 12 Years) With Moderate to Severe Persistent Asthma

NCT00529529 | Completed Phase 3 Results

• 1 other identifier: CQAB149B2338
• Study Type: interventional
• Target: 805
• Locations: 12 countries
• Sites: 126

Brief Summary

This study was designed to assess the safety of indacaterol (300 µg and 600 µg (2 x 300 μg capsules) once daily \[od\]), compared with salmeterol (50 μg twice a day \[b.i.d.\]), over 26 weeks, in patients with moderate to severe persistent asthma.

Conditions

Asthma

Keywords

asthma; QAB149; indacaterol

Outcome Measures

Primary Outcomes (15)

• Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study

  Adverse events include asthma exacerbations. An asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with rescue oral or intravenous (IV) corticosteroids. Asthma worsening that required treatment with inhaled or nebulized short-acting β2-agonists or an increase in inhaled corticosteroids only was not considered an asthma exacerbation.

  Baseline (Day 1) to end of study (Week 26)

• Systolic Blood Pressure 1 Hour Post-dose at Day 1

  Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and forced expiratory volume in 1 second (FEV1) pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Day 1

• Systolic Blood Pressure 1 Hour Post-dose at Week 12

  Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• Diastolic Blood Pressure 1 Hour Post-dose at Day 1

  Diastolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. Phase V Korotkoff sounds were used for determination of diastolic pressure. The analysis included baseline diastolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Day 1

• Diastolic Blood Pressure 1 Hour Post-dose at Week 12

  Diastolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. Phase V Korotkoff sounds were used for determination of diastolic pressure. The analysis included baseline diastolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1

  The QTc interval (in milliseconds, ms) is calculated from electrocardiogram (ECG) data collected 1 hour post-dose using Fridericia's formula: QTc = QT/RR\^0.33. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves. ECGs included all 12 standard leads and a Lead II rhythm strip of at least 10-second duration. All results were sent to a central laboratory for review by a cardiologist. The analysis included baseline QTc interval and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Day 1

• Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12

  The QTc interval (in milliseconds, ms) is calculated from electrocardiogram (ECG) data collected 1 hour post-dose using Fridericia's formula: QTc = QT/RR\^0.33. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves. ECGs included all 12 standard leads and a Lead II rhythm strip of at least 10-second duration. All results were sent to a central laboratory for review by a cardiologist. The analysis included baseline QTc interval and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21

  The QTc interval (in milliseconds, ms) is calculated from electrocardiogram (ECG) data collected 1 hour post-dose using Fridericia's formula: QTc = QT/RR\^0.33. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves. ECGs included all 12 standard leads and a Lead II rhythm strip of at least 10-second duration. All results were sent to a central laboratory for review by a cardiologist. The analysis included baseline QTc interval and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 21

• 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12

  Continuous 24 hour electrocardiography (Holter monitoring) was conducted in a subset of patients at designated study centers, and was used to calculate the mean heart rate (in beats per minute, bpm). Patients returned the Holter monitor recorder to the clinic the morning after the 24 hour recording was complete. The results of Holter monitoring were processed centrally. The analysis included baseline 24 hour mean heart rate and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26

  Continuous 24 hour electrocardiography (Holter monitoring) was conducted in a subset of patients at designated study centers, and was used to calculate the mean heart rate (in beats per minute, bpm). Patients returned the Holter monitor recorder to the clinic the morning after the 24 hour recording was complete. The results of Holter monitoring were processed centrally. The analysis included baseline 24 hour mean heart rate and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 26

• Serum Potassium 1 Hour Post-dose at Day 1

  Serum potassium (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline serum potassium and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Day 1

• Serum Potassium 1 Hour Post-dose at Week 12

  Serum potassium (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline serum potassium and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• Blood Glucose 1 Hour Post-dose at Day 1

  Blood glucose (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline blood glucose and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Day 1

• Blood Glucose 1 Hour Post-dose at Week 12

  Blood glucose (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline blood glucose and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

  Week 12

• Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study

  A clinically significant asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with systemic corticosteroids. This includes events recorded on the asthma exacerbation clinical report form (CRF) page and events recorded on the adverse events CRF page with "asthma" as a key word in the preferred term.

  Baseline (Day 1) to end of study (Week 26)

Secondary Outcomes (2)

• Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85

  24 hours post-dose at Week 12 + 1 day, Day 85

• Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study

  Baseline (Day 1) to end of study (Week 26)

Study Arms (3)

Indacaterol 300 μg

EXPERIMENTAL

Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 07:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol 300 μg; Drug: Placebo to indacaterol; Drug: Placebo to salmeterol

Indacaterol 600 μg

EXPERIMENTAL

Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 07:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol 300 μg; Drug: Placebo to salmeterol

Salmeterol 50 μg

ACTIVE COMPARATOR

Patients received salmeterol 50 μg delivered via the salmeterol proprietary dry powder inhalation device bis in die (bid, twice daily), once in the morning (between 07:00 and 11:00 AM) and once in the evening (between 7:00 and 11:00 PM). In addition to salmeterol 50 μg, patients received 2 indacaterol placebo inhalations in the morning. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Salmeterol 50 μg; Drug: Placebo to indacaterol

Interventions

Indacaterol 300 μg DRUG

Indacaterol was supplied as powder filled capsules together with a single dose dry powder inhaler (SDDPI).

Indacaterol 300 μg; Indacaterol 600 μg

Salmeterol 50 μg DRUG

Salmeterol was supplied as powder filled capsules together with the manufacturer's proprietary dry powder inhalation device.

Salmeterol 50 μg

Placebo to indacaterol DRUG

Placebo to indacaterol was supplied as powder filled capsules together with a single dose dry powder inhaler (SDDPI).

Indacaterol 300 μg; Salmeterol 50 μg

Placebo to salmeterol DRUG

Placebo to salmeterol was supplied as powder filled capsules together with the manufacturer's proprietary dry powder inhalation device.

Indacaterol 300 μg; Indacaterol 600 μg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged ≥ 12 years (or ≥ 18 years depending upon regulatory and/or Institutional Review Board/Independent Ethics Committee/Research Ethics Board \[IRB/IEC/REB\] approval) who have signed an informed consent form.
• Patients with moderate to severe persistent asthma, diagnosed according to the Global Initiative for Asthma (GINA) guidelines (Updated 2006) and who additionally meet the following criteria:
• Patients who have used treatment with a bronchodilator, either regularly or on-demand, and who had used a daily dose of at least 100 μg beclomethasone dipropionate (or equivalent) for at least 1 month prior to screening.
• Patients whose forced expiratory volume in 1 second (FEV1) is ≥ 50% of the predicted normal value.
• Patients with documented (in the previous 6 months) or who demonstrate (prior to randomization) a ≥ 12% and at least 200 ml increase in FEV1, after inhaling 200 μg salbutamol.

You may not qualify if:

• Pregnant or nursing (lactating) women and women of child-bearing potential UNLESS they meet pre-specified definitions of post-menopausal or are using pre-specified acceptable methods of contraception.
• Patients who have used tobacco products within the 12 month period prior to screening, or who have a smoking history of greater than 10 pack years.
• Patients who suffer from chronic obstructive pulmonary disease (COPD) as diagnosed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2006).
• Patients who have had emergency room treatment for an acute asthma attack in the 6 weeks prior to screening or who have been hospitalized for an acute asthma attack in the 6 months prior to screening, or at any time between screening and Week 1.
• Patients with diabetes Type I or those with uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or glycosylated hemoglobin (HbA1C) \> 8.0% measured at screening.
• Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition or a clinically relevant laboratory abnormality that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.
• Patients with a history of long QT syndrome, or whose QTc interval (Bazett's formula) is prolonged to \> 450 ms (males) or \> 470 ms (females).
• Certain medications for asthma and allied conditions such as long-acting bronchodilators must not be used prior to screening and for a pre-specified minimum washout period.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (126)

Novartis Investigator Site

Glendale, Arizona, 85306, United States

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Phoenix, Arizona, 85306, United States

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Encinitas, California, 92024, United States

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Huntington Beach, California, 92647, United States

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Long Beach, California, 90806, United States

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Long Beach, California, 90808, United States

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Los Angeles, California, 90025, United States

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Oakland, California, 94609, United States

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Orange, California, 92868, United States

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Palmdale, California, 93551, United States

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San Diego, California, 92120, United States

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San Diego, California, 92123, United States

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Walnut Creek, California, 94598, United States

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Denver, Colorado, 80206, United States

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Denver, Colorado, 80230, United States

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Englewood, Colorado, 80112, United States

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Lakewood, Colorado, 80401, United States

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Brandon, Florida, 33511, United States

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Largo, Florida, 33770, United States

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Miami, Florida, 33143, United States

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Panama City, Florida, 32405, United States

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Pensacola, Florida, 32503, United States

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Pensacola, Florida, 32514, United States

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Tamarac, Florida, 33321, United States

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Albany, Georgia, 31707, United States

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Stockbridge, Georgia, 30281, United States

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Overland Park, Kansas, 66210, United States

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Overland Park, Kansas, 66215, United States

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Topeka, Kansas, 66606, United States

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Florence, Kentucky, 41017, United States

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Baltimore, Maryland, 21236, United States

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Wheaton, Maryland, 20902, United States

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North Dartmouth, Massachusetts, 02747, United States

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Ann Arbor, Michigan, 48106, United States

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Ypsilanti, Michigan, 48197, United States

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Springfield, Missouri, 65807, United States

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St Louis, Missouri, 63141, United States

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Omaha, Nebraska, 68130, United States

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Omaha, Nebraska, 68131, United States

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Northfield, New Jersey, 08225, United States

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Rockville Centre, New York, 11570, United States

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Charlotte, North Carolina, 28207, United States

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High Point, North Carolina, 27262, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45252, United States

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Toledo, Ohio, 43617, United States

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Edmond, Oklahoma, 73003, United States

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Oklahoma City, Oklahoma, 73120, United States

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Greenville, South Carolina, 29615, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77024, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77054, United States

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Houston, Texas, 77070, United States

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Kirkland, Washington, 98034, United States

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Seattle, Washington, 98105, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Rosario, Argentina

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San Miguel de Tucumán, Argentina

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Halifax, Canada

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London, Canada

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Mississauga, Canada

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Montreal, Canada

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Ste-Foy, Canada

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Brno, Czechia

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Prague, Czechia

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Prague, Czechia

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Brest, France

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Castelnau-le-Lez, France

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Chauny, France

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Paris, France

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Tarbes, France

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Vandœuvre-lès-Nancy, France

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Berlin, Germany

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Bochum, Germany

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Borstel, Germany

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Geesthacht, Germany

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Hamburg, Germany

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Kiel, Germany

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Leipzig, Germany

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Lübeck, Germany

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Mainz, Germany

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Marburg, Germany

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Neumünster, Germany

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Neuss, Germany

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Schwetzingen, Germany

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Wiesloch, Germany

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Wittem, Germany

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Debrecen, Hungary

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Nyíregyháza, Hungary

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Sopron, Hungary

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Szombathely, Hungary

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Tatabánya, Hungary

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Brescia, Italy

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Catania, Italy

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Modena, Italy

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Parma, Italy

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Pietra Ligure, Italy

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Pisa, Italy

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Terni, Italy

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Torino, Italy

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Trieste, Italy

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Lima, Peru

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Bardejov, Slovakia

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Bratislava, Slovakia

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Košice, Slovakia

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Nitra, Slovakia

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Trenčín, Slovakia

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Alicante, Spain

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Barcelona, Spain

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Begonte, Spain

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Cadiz, Spain

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Cáceres, Spain

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Granollers, Spain

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Hostalets de Balenyà, Spain

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Illescas, Spain

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L'Hospitalet de Llobregat, Spain

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Mataró, Spain

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Oviedo, Spain

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Seville, Spain

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Valencia, Spain

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Ankara, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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MeSH Terms

Conditions

Asthma

Interventions

indacaterol; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2007
• First Posted: September 14, 2007
• Study Start: September 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 29, 2011
• Results First Posted: August 19, 2011

Record last verified: 2011-08

Locations

FR (6); DE (15); IT (9); US (56); TU (4); HU (5); CZ (3); SL (5); CA (5); AR (4); ES (13); PE (1)