Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Arcapta
Indacaterol 300 µg · 5 trials · 3 indications
The number of participants with newly occurring or worsening clinically notable vital sign: Pulse Rate in beats per minute (bpm) at anytime post baseline (BL) by treatment. Low Pulse Rate was defined as a pulse rate \<40 bpm or \<= to 50 bpm and a decrease from baseline \>= to 15 bpm. High Pulse Rate was defined as a pulse rate \>130 bpm or \>= to 120 bpm and an increase from baseline \>= to 15 bpm.
The number of participants with newly occurring or worsening clinically notable vital sign: Systolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Systolic Blood Pressure was defined as a systolic blood pressure measurement: \<75 mmHg or \<= to 90 mmHg and a decrease from baseline \>= to 20 mmHg. A High Systolic Blood Pressure was defined as a systolic blood pressure measurement: \>200 mmHg or \>= to 180 mmHg and an increase from baseline \>= to 20 mmHg.
The number of participants with newly occurring or worsening clinically notable vital sign: Diastolic blood pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: \<40 mmHg or \<= to 50 mmHg and a decrease from baseline \>= to 15 mmHg. A High Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: \>115 mmHg or \>= to 105 mmHg and an increase from baseline \>= to 15 mmHg.
The number of participants with newly occurring or worsening clinically notable QTc Interval value at anytime post baseline. The QTc interval is calculated using Fridericia's formula: QTc= QT/cube root RR. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves in milliseconds (ms). Notable QTc interval \>450 ms for males and \>470 ms for females. The maximum QTc increase from baseline at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and \>60 ms.
The least squares mean of the serum potassium in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate.
The least squares mean of the blood glucose in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate.
At the end of each 3 week treatment period, patients completed constant-load cycle ergometry testing at a work-rate of 75% of the Wmax determined at Screening. This work-rate was maintained until symptom limitation caused the patient to stop exercising. The time from the start of loaded pedaling until the patient stopped exercising was recorded.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of each treatment period. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Inspiratory capacity (IC) at peak time and at isotime were the primary pharmacodynamic (PD) variables of interest. IC was measured at two minute intervals during exercise. Isotime was defined as the time the subject was still exercising in the shortest of all sub-maximal exercise tests (3-minutes resting pedaling, 3-minutes unloaded pedaling and exercise with loaded pedaling). Peak time was defined as the last measurement taken in the exercise period. The primary analysis consisted of a linear mixed effects model with baseline IC measurement as covariate.
| Arm | Type | Description |
|---|---|---|
| Indacaterol 300 µg | EXPERIMENTAL | Indacaterol 300 μg once a day (o.d.) delivered via single dose dry powder inhaler (SDDPI). Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study. |
| Salmeterol 50 µg | ACTIVE_COMPARATOR | Salmeterol 50 μg twice a day (b.i.d.) delivered via Diskus®. Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study. |
| Indacaterol 300 μg followed by placebo | EXPERIMENTAL | Patients first received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning for 3 weeks. After a 3-week washout period, patients received placebo delivered od via a SDDPI in the morning for 3 weeks. 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. |
| Placebo followed by indacaterol 300 μg | EXPERIMENTAL | Patients first received placebo delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning for 3 weeks. After a 3-week washout period, patients received indacaterol 300 μg delivered od via a SDDPI in the morning for 3 weeks. 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. |
| Indacaterol 300 μg - placebo to indacaterol - salmeterol 50 μg | EXPERIMENTAL | In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| Placebo to indacaterol - salmeterol 50 μg - indacaterol 300 μg | EXPERIMENTAL | In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| Salmeterol 50 μg - indacaterol 300 μg - placebo to indacaterol | EXPERIMENTAL | In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| Placebo to indacaterol - indacaterol 300 μg - salmeterol 50 μg | EXPERIMENTAL | In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| Indacaterol 300 μg - salmeterol 50 μg - placebo to indacaterol | EXPERIMENTAL | In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| Salmeterol 50 μg - placebo to indacaterol - indacaterol 300 μg | EXPERIMENTAL | In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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. |
| 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. |
| 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. |
| 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. |
| Sequence 1: Indacaterol 300μg followed by Placebo | EXPERIMENTAL | In period I, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study. |
| Sequence 2 : Placebo followed by Indacaterol 300μg | EXPERIMENTAL | In period I, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study. |
| Name | Type | Description |
|---|---|---|
| Indacaterol 300 µg | DRUG | Indacaterol 300 µg once daily (od) via SDDPI |
| Salmeterol 50 µg | DRUG | Salmeterol 50 µg twice daily (bid) via Diskus® |
| Indacaterol 300 μg | DRUG | Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device. |
| Placebo | DRUG | Placebo was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device. |
| Placebo to indacaterol | DRUG | Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI). |
| Salmeterol 50 μg | DRUG | Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI). |
| Placebo to salmeterol | DRUG | Placebo to salmeterol was supplied as powder filled capsules together with the manufacturer's proprietary dry powder inhalation device. |
| Indacaterol 300μg | DRUG | 300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device |
Inclusion Criteria: 1\. Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines) and: * Smoking history of at least 20 pack-years * Post-bronchodilator FEV1 \<80% and ≥30% of the predicted normal value * Post-bronchodilato...
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| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Novartis AG Sponsored ADR | NVS | 5 | PHASE3 | QVM149, QMF149, Glycopyrronium bromide |
| GSK plc Sponsored ADR | GSK | 10 | PHASE3 | Trelegy Ellipta, Depemokimab, HFA-152a, GSK5784283, Ventolin |
| Teva Pharmaceutical Industries Limited Sponsored ADR | TEVA | 4 | PHASE3 | TEV-56248, ProAir (albuterol sulfate eMDPI), Budesonide/Formoterol SPIROMAX, Reslizumab |
| Sanofi SA Sponsored ADR | SNY | 8 | PHASE3 | Dupilumab, Lunsekimig |
| AstraZeneca PLC | AZN | 28 | PHASE3 | Benralizumab, Tezepelumab, Budesonide/formoterol, Albuterol/budesonide, PT007 |
| Pfizer Inc. | PFE | 4 | PHASE3 | Tilrekimig, PF-07275315, PF-08103402 |
| Generate Biomedicines, Inc. | GENB | 3 | PHASE3 | GB-0895 |
| Kymera Therapeutics, Inc. | KYMR | 1 | PHASE2 | KT-621 |
| Eli Lilly and Company | LLY | 1 | PHASE2 | Brenipatide |
| Incyte Corporation | INCY | 1 | PHASE2 | povorcitinib |
| Upstream Bio, Inc. | UPB | 1 | PHASE2 | Verekitug |
| Arrowhead Pharmaceuticals, Inc. | ARWR | 1 | PHASE2 | ARO-RAGE |
| Amgen Inc. | AMGN | 1 | PHASE1 | AMG 691 |
| Johnson & Johnson | JNJ | 1 | PHASE2 | JNJ-95597528 |
| Apogee Therapeutics, Inc. | APGE | 1 | PHASE1 | APG777 |
| Celldex Therapeutics, Inc. | CLDX | 1 | PHASE1 | CDX-622 |
Indacaterol 300 µg is an investigational small molecule developed by Novartis AG for respiratory conditions. It is being studied in asthma and chronic obstructive pulmonary disease (COPD). The 300 µg dose refers to the amount delivered per inhalation. It is not yet approved and remains in clinical development.
Indacaterol 300 µg is being studied for the treatment of chronic obstructive pulmonary disease (COPD). Clinical trials have enrolled patients with moderate to severe COPD, including studies of lung function, exercise endurance, and lung hyperinflation. It is also being investigated in asthma. The drug is investigational and has not been approved for any use.
Indacaterol 300 µg targets ADRB2, the beta-2 adrenergic receptor. It acts as an agonist at this receptor. ADRB2 agonism is the mechanism studied in the COPD trials, which assessed lung function and breathlessness outcomes in patients with the disease.
Indacaterol 300 µg is developed by Novartis AG, which trades under the ticker NVS. Novartis sponsored the clinical trials evaluating the drug in chronic obstructive pulmonary disease and asthma.
Indacaterol 300 µg is in Phase 3 development. Four clinical trials have been completed, including three Phase 3 studies and one Phase 2 study, with no active trials currently listed. The drug is investigational and has not been approved by the FDA.
Four completed trials have studied Indacaterol 300 µg. These include NCT00876694, a Phase 3 confirmatory COPD study in Japan; NCT00636961, a Phase 2 study of lung hyperinflation in Germany; NCT00622635, a Phase 3 crossover lung function study; and NCT00620022, a Phase 3 exercise endurance study. Total enrollment was 805 patients.