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

Novartis

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: Salmeterol 50 μg; Drug: Placebo to salmeterol; Drug: Indacaterol 300 μg; Drug: Placebo to indacaterol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00529529

CQAB149B2338

Details and patient eligibility

About

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.

Enrollment: 805 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.

2. 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.

Exclusion criteria

1. 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.
2. 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.
3. Patients who suffer from chronic obstructive pulmonary disease (COPD) as diagnosed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2006).
4. 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.
5. 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.
6. 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.
7. 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).
8. 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.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

805 participants in 3 patient groups

Indacaterol 300 μg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to salmeterol

Drug: Placebo to indacaterol

Drug: Indacaterol 300 μg

Indacaterol 600 μg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to salmeterol

Drug: Indacaterol 300 μg

Salmeterol 50 μg

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to indacaterol

Drug: Salmeterol 50 μg