Clinical Study Results

Improved breathing for up to 12 hours with twice-daily LONHALA MAGNAIR

for people with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

LONHALA MAGNAIR was studied in two 12-week, randomized, double-blind, placebo-controlled, parallel-group confirmatory studies (Study 1 and Study 2) to evaluate the efficacy of LONHALA MAGNAIR vs placebo in patients with COPD. The primary efficacy end point was the change from baseline trough FEV1 at Day 84 compared with placebo.1

Secondary end points were to perform serial spirometric evaluations throughout the 12-hour dosing intervals in a subset of subjects on Day 1 and Day 84, and to measure improvement in health-related quality of life using the St. George's Respiratory Questionnaire (SGRQ).1,2

Significant improvement in trough FEV1 at Week 12

LS mean change from baseline in trough FEV1 at Week 12 in two 12-week, randomized, double-blind, placebo-controlled, parallel-group confirmatory studies (Study 1 and Study 2) to evaluate the efficacy of LONHALA MAGNAIR vs placebo in patients with COPD. Both studies were conducted with LONHALA MAGNAIR 25 mcg and 50 mcg twice daily and placebo twice daily. The LONHALA MAGNAIR 25 mcg arm vs placebo arm is displayed here (the 50 mcg dosage strength did not provide significant additional benefit and is not presented here or approved for use). The primary efficacy end point was the change from baseline in trough FEV1 at Day 84 compared with placebo.

Trough FEV1 at Week 12
(all collected and on-treatment)
1-4

 

Trough FEV1 is the mean of FEV1 at 45 min and 15 min before the morning dose.3

The on-treatment population was defined as a population that included only data collected while the subjects were taking the study drug.

  • The all collected data (primary analysis) shown represent patients who discontinued LONHALA MAGNAIR but completed study visits and may have been taking other COPD therapies5

 

Significant improvement in trough FEV1 vs placebo, regardless of LABA background therapy4,5

of subjects were on background LABA therapy5

Approximately 30% of subjects were on background LABA therapy. Patients on background LABA therapy taking 25 mcg of LONHALA MAGNAIR had an FEV1 baseline of 1.2464 L, with a mean placebo-adjusted trough improvement of 0.0991 L at 12 weeks. Patients not on background LABA therapy taking 25 mcg of LONHALA MAGNAIR had an FEV1 baseline of 1.3576 L, with a mean placebo-adjusted trough improvement of 0.0916 L at 12 weeks.

The most common adverse events reported in ≥2% of patients taking LONHALA MAGNAIR, and occurring more frequently than in patients taking placebo, were dyspnea (4.9% vs 3.0%) and urinary tract infection (2.1% vs 1.4%).


Improved lung function maintained over time

12-week studies: LS mean change from baseline trough FEV1 over time at Week 12 in two pooled 12-week, randomized, double-blind, placebo-controlled, parallel-group confirmatory studies (Study 1 and Study 2) to evaluate the efficacy of LONHALA MAGNAIR vs placebo in patients with COPD. Both studies were conducted with LONHALA MAGNAIR 25 mcg and 50 mcg twice daily and placebo twice daily. The LONHALA MAGNAIR 25 mcg arm vs placebo arm is displayed here (the 50 mcg dosage strength did not provide significant additional benefit and is not presented here or approved for use). The primary efficacy end point was the change from baseline in trough FEV1 at Day 84 compared with placebo.

Significant and clinically important improvement in lung function was maintained through 12 weeks vs placebo4,5

LONHALA MAGNAIR should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD or used as rescue therapy for acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting beta2-agonist.

FEV1=forced expiratory volume in 1 second; LABA=long-acting beta2-agonist; LS=least squares.

 

Sustained bronchodilation over 12 hours on Day 1

Mean change from baseline in FEV1 over time on Day 1 in a substudy population in a 12-week, randomized, double-blind, placebo-controlled, parallel-group, confirmatory study (Study 1) to evaluate the efficacy of LONHALA MAGNAIR vs placebo in patients with COPD. The study was conducted with LONHALA MAGNAIR 25 mcg and 50 mcg twice daily and placebo twice daily. The LONHALA MAGNAIR 25 mcg arm vs placebo arm is displayed here (the 50 mcg dosage strength is not approved for use). The primary efficacy end point was the change from baseline in trough FEV1 at Day 84 compared with placebo.

Serial spirometric evaluations throughout the 12-hour dosing interval were performed in a subset of subjects on Day 1 and Day 84.

FEV1 on Day 1
(all collected substudy population)
1,2

FEV1=forced expiratory volume in 1 second.

Dosed twice daily, morning and evening, for up to 24 hours of symptom control1


As with other inhaled medicines, LONHALA MAGNAIR can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with LONHALA MAGNAIR, it should be treated immediately with an inhaled, short-acting bronchodilator; LONHALA MAGNAIR should be discontinued immediately and alternative therapy instituted.

St. George’s Respiratory Questionnaire (SGRQ) measures the impact of COPD on health-related quality of life

Improvement in SGRQ is based on the total score and not the individual subcomponents.

 

Meaningful improvement is defined as ≥4 point decrease in SGRQ total score1


Health-related quality of life was measured using SGRQ total score in two 12-week, randomized, double-blind, placebo-controlled, parallel-group confirmatory studies (Study 1 and Study 2) to evaluate the efficacy of LONHALA MAGNAIR vs placebo in patients with COPD. SGRQ is a disease-specific, 50-item, patient-reported outcomes instrument designed to measure symptoms, activities, and impacts on daily life in patients with obstructive airway disease.

Meaningful improvement in health-related quality of life as measured by SGRQ total score

>40% of patients reported a meaningful improvement of ≥4 points in SGRQ total score regardless of background LABA therapy for both all collected and on-treatment analyses vs placebo (>29%)1

~30% of subjects were on background LABA therapy

Percentage of patients with a meaningful improvement in SGRQ total score1,5

 

Approximately 30% of subjects were on background LABA therapy. Patients on background LABA therapy taking 25 mcg of LONHALA MAGNAIR had an FEV1 baseline of 1.2464 L, with a mean placebo-adjusted trough improvement of 0.0991 L at 12 weeks. Patients not on background LABA therapy taking 25 mcg of LONHALA MAGNAIR had an FEV1 baseline of 1.3576 L, with a mean placebo-adjusted trough improvement of 0.0916 L at 12 weeks.

Results are derived from post hoc subanalyses.


Immediate hypersensitivity reactions have been reported with LONHALA MAGNAIR. If signs occur, discontinue LONHALA MAGNAIR immediately and institute alternative therapy.

LONHALA MAGNAIR should be used with caution in patients with narrow-angle glaucoma and in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema) and of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Patients should be instructed to consult a physician immediately should any of these signs or symptoms develop.

FEV1=forced expiratory volume in 1 second; LABA=long-acting beta2-agonist.

LONHALA MAGNAIR Safety Profile

Efficacy and safety were assessed in two 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trials in subjects with moderate to very severe COPD. Subjects were randomized using a 1:1:1 ratio to 1 of 3 treatments: placebo BID, LONHALA MAGNAIR 25 mcg BID, and glycopyrrolate 50 mcg BID. Safety end points included the number and percentage of subjects with treatment-emergent adverse events (TEAEs) and serious AEs, and the number and percentage of subjects who discountinued treatment due to TEAEs.4,6

Pooled analysis of two 12-week trials

  • The safety of LONHALA MAGNAIR was evaluated in two 12-week, randomized, double-blind, placebo-controlled, parallel group, confirmatory studies, and a 48-week,  long-term, open-label safety clinical trial

Adverse reactions with ≥2% incidence and higher than placebo1

 

  • The incidence of discontinuation due to adverse reactions was greater for placebo (9.3%) than for LONHALA MAGNAIR (5.1%)6

48-week, long-term, open-label safety clinical trial1

  • Adverse reactions reported in a randomized, open-label, active-controlled, parallel-group, 48-week, long-term safety trial (N=620) were consistent with those observed in the 12-week studies (Study 1 and Study 2)
    • Additional adverse reactions with LONHALA MAGNAIR (50 mcg BID) that occurred at a frequency greater than those seen in either active treatment dose in the pooled 12-week studies and ≥2% were diarrhea, edema peripheral, bronchitis, nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, urinary tract infection, back pain, headache, COPD, cough, dyspnea, oropharyngeal pain, and hypertension

BID=twice daily.


 

References:

  1. LONHALA MAGNAIR  [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; 2018.
  2. Data on file. Glycopyrrolate Inhalation Solution Protocol Sun101-301 Clinical Study Report. NCT identifier:02347761. Sunovion Pharmaceuticals Inc.
  3. Data on file. Glycopyrrolate Inhalation Solution Protocol Sun101-302 Clinical Study Report. NCT identifier:02347774. Sunovion Pharmaceuticals Inc. 
  4. Kerwin E, Donohue JF, Goodin T, et al. Efficacy and safety of glycopyrrolate/eFlow® CS (nebulized glycopyrrolate) in moderate-to-severe COPD: results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trials. Respir Med. 2017;132:238–250.
  5. Data on file. Integrated Summary of Efficacy. 11-117. Sunovion Pharmaceuticals Inc.
  6. Data on file. Integrated Summary of Safety. 156. Sunovion Pharmaceuticals Inc.

Important Safety Information & Indication 

Important Safety Information
 

LONHALA MAGNAIR is contraindicated in patients with a hypersensitivity to glycopyrrolate or to any of the ingredients.

LONHALA MAGNAIR should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD or used as rescue therapy for acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting beta2-agonist.

As with other inhaled medicines, LONHALA MAGNAIR can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with LONHALA MAGNAIR, it should be treated immediately with an inhaled, short-acting bronchodilator; LONHALA MAGNAIR should be discontinued immediately and alternative therapy instituted.

Immediate hypersensitivity reactions have been reported with LONHALA MAGNAIR. If signs occur, discontinue LONHALA MAGNAIR immediately and institute alternative therapy.

LONHALA MAGNAIR should be used with caution in patients with narrow-angle glaucoma and in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema) and of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Patients should be instructed to consult a physician immediately should any of these signs or symptoms develop.

The most common adverse events reported in ≥2% of patients taking LONHALA MAGNAIR, and occurring more frequently than in patients taking placebo, were dyspnea (4.9% vs 3.0%) and urinary tract infection (2.1% vs 1.4%).

LONHALA solution is for oral inhalation only and should not be injected or swallowed. LONHALA vials should only be administered with MAGNAIR.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional information, please see full Prescribing Information and Patient Information for LONHALA MAGNAIR at www.sunovionprofile.com/lonhala-magnair.


Indication
 

LONHALA® MAGNAIR® (glycopyrrolate) is an anticholinergic indicated for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.