Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as NVA237 (glycopyrronium bromide), Glycopyrronium bromide
NVA237 · 15 trials · 4 indications
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23hours 15min and 23 hours 45min post dosing. ANCOVA model: Trough FEV1 = treatment + baseline FEV1 + baseline Inhaled corticosteroid (ICS) use (Yes/No) + FEV1 reversibility components + baseline smoking status + region + center (region). This analysis excluded values within 6 hours of rescue medication use or 7 days of systemic corticosteroid use.
Baseline FEV1 was defined as the average of the -45 min and -15 min FEV1 values taken on day 1 prior to the first dose of study medication. Trough FEV1 was defined as the mean of the post-dose 23 h 15 min and the 23 h 45 min FEV1 values. FEV1 was measured using central spirometry according to ATS/ERS standardization. Trough FEV1 was analyzed using a MIXED model for the full analysis set population. The model contained treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation of short acting bronchodilator, FEV1 45 min post inhalation of short acting bronchodilator and baseline inhaled corticosteroids (ICS) use as covariates.
SMETT is an exercise procedure where the patient cycles at 80% of the maximum workload (Wmax )value achieved at the Incremental exercise test. During this test, the patient will cycle at a constant load. Exercise endurance time was from commencement of loaded pedaling to stopping exercise. The analysis-of covariance model included the sequence, period, and treatment as fixed factors, the baseline value as covariate and the patient as a random effect.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included baseline FEV1 measurement, baseline inhaled corticosteroid use (Yes/No), FEV1 prior to inhalation of short-acting β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured by spirometry.
To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared to placebo in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post -dose) following 1 week of treatment in the respective treatment period. Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 15 min and 23h 45 min post dose.
Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change is FEV1 from predose (day 1) to the readings taken 0-24 hours post dose on day 14. The variable was analyzed with an analysis-of-covariance model which included baseline FEV1 value as a covariate.
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing.
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Blood samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Plasma, Analyte: NVA237
Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237
Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237
Samples will be collected at various time points on each visit day; Compound: NVA237 100ug, Matrix: Urine, Analyte: NVA237
| Arm | Type | Description |
|---|---|---|
| NVA237 | EXPERIMENTAL | NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks |
| Placebo | PLACEBO_COMPARATOR | Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks. |
| NVA237 dose 1 | EXPERIMENTAL | NVA237 dose 1 |
| Long-acting beta 2-agonist (LABA) | ACTIVE_COMPARATOR | QAB149 |
| Tiotropium | ACTIVE_COMPARATOR | Tiotropium 18 μg once a day and placebo to NVA237 once a day during 85 days. Salbutamol/albuterol was provided as rescue medication. |
| NVA237 followed by Placebo | EXPERIMENTAL | Period 1: 50 μg NVA237 via NEOHALER inhaler device for 21 days Period 2: Matching placebo via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study. |
| Placebo followed by NVA237 | EXPERIMENTAL | Period 1: Matching placebo of NVA237 via NEOHALER inhaler device for 21 days Period 2: 50 μg NVA237 via NEOHALER inhaler device for 21 days The washout period ran for 14 to 28 days between treatment periods. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. Salbutamol (albuterol) was used as rescue medication throughout the study. |
| Glycopyrronium bromide | EXPERIMENTAL | Glycopyrronium bromide 50µg delivered once daily via Single Dose Dry Powder Inhaler (SDDPI). At visit 1 all patients were provided with a short acting β2-agonist (salbutamol/albuterol) which they were instructed to use throughout the study as rescue medication. |
| Glycopyrronium bromide 50 μg | EXPERIMENTAL | Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 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 to glycopyrronium bromide | PLACEBO_COMPARATOR | Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 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. |
| Tiotropium 18 μg | ACTIVE_COMPARATOR | Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 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. |
| Glycopyrronium 25μg | EXPERIMENTAL | Glycopyrronium 25μg for two weeks |
| Glycopyrronium 12.5μg | EXPERIMENTAL | Glycopyrronium 12.5μg for two weeks |
| 1(NVA237 50 ug/NVA237 25 ug/placebo) | OTHER | Treatment sequence: NVA 237 50 ug, 25 ug and placebo |
| 2(NVA237 50 ug/placebo/NVA237 25 ug) | OTHER | Treatment sequence: NVA 237 50 ug, placebo and 25 ug |
| 3 (NVA237 25 ug/NVA237 50 ug/placebo) | OTHER | Treatment sequence: NVA237 25 ug, 50 ug and placebo |
| 4 (NVA237 25 ug/placebo/NVA237 50 ug) | OTHER | Treatment sequence: NVA 237 25 ug, placebo and 50 ug |
| 5 (placebo/NVA237 50 ug/ NVA237 25 ug) | OTHER | Treatment sequence: Placebo, NVA237 50 ug and 25 ug |
| 6 (placebo/ NVA237 25 ug/NVA237 50 ug) | OTHER | Treatment sequence: placebo, NVA237 25 ug and 50 ug |
| Placebo then NVA237 50μg | PLACEBO_COMPARATOR | Placebo 50 μg capsules followed by NVA237 50 μg capsules for inhalation once daily with Concept 1 device. |
| NVA237 50μg then placebo | EXPERIMENTAL | NVA237 50 μg capsules followed by matching placebo 50 μg capsules for inhalation once daily with Concept 1 device. |
| NVA237 12.5 µg | EXPERIMENTAL | 12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. |
| NVA237 25 µg | EXPERIMENTAL | 25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. |
| NVA237 50 µg | EXPERIMENTAL | 50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. |
| NVA237 100 µg | EXPERIMENTAL | 100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. |
| Tiotropium 18 µg | ACTIVE_COMPARATOR | 18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence. |
| Healthy volunteers | EXPERIMENTAL | control group receiving 100 μg NVA237 |
| Mild renal impairment | EXPERIMENTAL | (eGFR 50-80 mL/min/1.73m2) receiving 100 μg NVA237 |
| Moderate renal impairment | EXPERIMENTAL | (eGFR 30-49 mL/min/1.73m2) receiving 100 μg NVA237 |
| Severe renal impairment | EXPERIMENTAL | (eGFR \<30 mL/min1.73m2) receiving 100 μg NVA237 |
| End-stage subjects requiring dialysis (ESRD) | EXPERIMENTAL | receiving 100 μg NVA237 |
| 1 | EXPERIMENTAL | NVA237 |
| 2 | EXPERIMENTAL | NVA237 |
| 3 | EXPERIMENTAL | NVA237 |
| 4 | EXPERIMENTAL | NVA237 |
| 5 | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| NVA237 | DRUG | NVA237 (glycopyrronium bromide) as a powder for inhalation in single-dose capsules. |
| Placebo | DRUG | Placebo powder for inhalation in single-dose capsules (matching those for NVA237). |
| Long-acting beta 2-agonist (LABA) | DRUG | QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI |
| Tiotropium | DRUG | Tiotropium 18 μg once a day delivered via HandiHaler® device |
| Placebo to tiotropium | DRUG | Placebo to tiotropium 18 μg o.d. once a day delivered via HandiHaler® device. |
| Placebo to NVA237 | DRUG | Placebo to NVA237 50 μg once a day delivered via SDDPI |
| salbutamol/albuterol | DRUG | salbutamol/albuterol given as a rescue medication via inhaler when needed |
| Glycopyrronium bromide | DRUG | Glycopyrronium bromide 50µg was supplied as inhalation capsules for use via a Single Dose Dry Powder Inhaler (SDDPI) |
| Placebo to glycopyrronium bromide | DRUG | Placebo to glycopyrronium bromide was supplied in powder-filled capsules together with a single-dose dry-powder inhaler (SDDPI) device. |
| Glycopyrronium bromide 25ug | DRUG | 25μg Glycopyrronium bromide capsules for oral inhalation via Breezhaler |
| Glycopyrronium bromide 12.5ug | DRUG | 12.5ug Glycopyrronium bromide capsules for oral inhalation via Breezhaler |
| NVA237 (glycopyrronium bromide) | DRUG | In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose |
Inclusion criteria: 1. Patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with airflow obstruction of level 2 and 3 according to the current Global initiative for chronic Obstructive Lung Disease (GOLD) strategy (2011). 2. Patients with Forced Expiratory Volume in one se...
NVA237 is being studied for asthma, chronic obstructive pulmonary disease (COPD), and renal impairment. It is an investigational small molecule developed by Novartis AG. The clinical program includes trials in patients with asthma and COPD, with a combined enrollment of about 2,975 participants across completed studies.
NVA237 is a small molecule, and its development focuses on respiratory conditions including asthma and COPD. The program includes bronchodilator studies, such as NCT03137784, which evaluated bronchodilator effects and safety of glycopyrronium bromide in asthma. It has also been studied in COPD efficacy and long-term safety trials.
NVA237 is developed by Novartis AG, which trades under the ticker NVS. Novartis has sponsored the clinical program, including Phase 2 and Phase 3 studies in asthma and COPD. The trials have been conducted across multiple countries, including the United States, Belgium, Germany, Japan, Latvia, and Lithuania.
NVA237 is in Phase 2 development. The program includes completed Phase 2 and Phase 3 trials, but no active trials are currently listed. It is an investigational therapy and has not been approved by the FDA for any indication based on the available development information.
NVA237 has been evaluated in completed trials including NCT03137784, a Phase 2 asthma study; NCT01715298 and NCT01709864, Phase 3 COPD efficacy studies; and NCT01697696, a Phase 3 long-term safety study in COPD. All ten trials are completed, with no active studies ongoing.
Yes, NVA237 is also known as glycopyrronium bromide. The two names refer to the same investigational small molecule. Clinical trial titles use both NVA237 and glycopyrronium bromide, such as the Phase 2 asthma study NCT03137784, which evaluated glycopyrronium bromide at 25 ug and 50 ug once daily.