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Table 1 Summary Table of the glycopyrronium QTCF effects in the GLOW 1–6 trials (the GB in COPD airWays studies)[49]

From: A case report of QT prolongation with glycopyrronium bromide in a patient with chronic tamoxifen use

Aim of study; study size (N) Patient population Study intervention
Study comparator
QT prolongation
GLOW-1
Aim
 Efficacy, safety and tolerability of GB in moderate/severe COPD
Study type
 Randomized controlled trial double blind
Size
 n = 822
Inclusion criteria
 GOLD criteria—moderate to severe ≥40 years of age
 Smoking history of ≥10 pack-years
 Exclusion criteriaPost-bronchodilator FEV1 of <80 and ≥30 % of predicted FEV1/FVC ratio of <0.70
 Lower respiratory tract infection (RTI) within 6 weeks; concomitant pulmonary disease history of asthma or lung cancer
 Long QT syndrome: QTc >450 ms (males) or >470 (females)
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow—angle glaucoma
 History of alpha-1 antitrypsin
Intervention
 GB n = 552, completed 26 week trial n = 450
Comparator
 Placebo n = 270, completed 26 week trial n = 212
QTcF >500 ms
 GB: n = 0 (0 %)
Placebo: n = 0 (0 %)
 Increase of 30–60 ms
 GB: n = 59 (10.7 %)
Placebo n = 21 (7.9 %)
Increase of >60 ms
 GB: n = 6 (1.1 %)
 Placebo: n = 1 (0.4 %)
GLOW-2
Aim
 Efficacy, safety and tolerability of GB in moderate/severe COPD vs placebo vs tiotropium
Study type
 Randomized controlled trial (double blind)
Size
 n = 1066
Inclusion criteria
 Males and females ≥40 years of age
 Smoking history of ≥10 pack-years
 GOLD moderate-to-severe COPD
 Post-bronchodilator FEV1 ≥30 and <80 % of the predicted
 Post-broncho-dilator FEV1/FVC <0.70
Exclusion criteria
 Lower RTI 6 weeks prior
 Concomitant pulmonary disease
Intervention
 GB n = 529, completed 52 week trial n = 411
 Comparator
Placebo n = 269, completed 52 week trial n = 193
 Tiotropium n = 268 completed 52 week trial n = 206
QTcF >500 ms
 GB: n = 2 (0.4 %)
 Placebo: n = 2 (0.7 %)
 Tiotropium: n = 0 (0 %)
Increase of 30–60 ms:
 GB: n = 83 (15.8 %)
 Placebo: n = 39 (14.6 %)
 Tiotropium: n = 43 (16.2 %)
Increase of >60 ms
 GB: n = 1 (0.2 %)
 Placebo: n = 1 (0.4 %)
 Tiotropium: n = 0 (0 %)
  Pulmonary tuberculosis
  Bronchiectasis
  History of asthma
  Malignancy of any system
 Long QT syndrome or QTc >450 ms (males) or >470 (females)
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow-angle glaucoma
 History of a1-antitrypsin deficiency
 Active in pulmonary rehabilitation
 Contraindications for tiotropium or ipratropium or history of adverse reactions to inhaled anticholinergics
GLOW-3
Aim
Exercise tolerance with once daily GB
Study type
 Randomized Controlled Trial (Double blind)
Size
 n = 108
Inclusion criteria
 GOLD moderate to severe COPD
 Aged ≥ 40 years
 Smoking history ≥10 pack-years
 Post-bronchodilator FEV1 <80 %
 ≥40 % of predicted normal
 Post-bronchodilator FEV1/FVC of <70 %.
Exclusion criteria
 Lower RTI prior 6 weeks
 Oxygen for chronic hypoxemia
 Concomitant pulmonary disease
Intervention
 GB n = 55
Comparator
 Placebo n = 53
QTcF—not measured
  Pulmonary tuberculosis
  Bronchiectasis
  History of asthma
  Malignancy of any system
 Long QT syndrome QTc >450 ms for males or >470 ms for females,
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow-angle glaucoma
 Alpha-1 anti- trypsin deficiency
 Adverse reactions to inhaled anticholinergic agents, long- and short-acting alpha-agonists or
 Sympathomimetic amines
 Active pulmonary rehabilitation
GLOW-4
Aim
Efficacy, safety and tolerability of GB in moderate/severe COPD vs tiotropium in the Japanese Population
Study type
 Randomized controlled trial (Double blind)
Size
 n = 163
Inclusion criteria
 GOLD moderate-to-severe COPD
 Males and females ≥40 years of age
 Smoking history of ≥10 pack-years GOLD moderate-to-severe COPD
 Post-bronchodilator FEV1 ≥30 and
 <80 % of the predicted Post-broncho-dilator FEV1/FVC <0.70
Exclusion criteria
 Lower RTI prior 6 weeks
 Oxygen for chronic hypoxemia
 Concomitant pulmonary disease
Intervention
 GB n = 123
Comparator
 Placebo n = 40
QTcF—not measured
  Pulmonary tuberculosis
  Bronchiectasis
  History of asthma
  Malignancy of any system
 Long QT syndrome QTc >450 ms for males or >470 ms for females,
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow-angle glaucoma
 Alpha-1 anti- trypsin deficiency
 Adverse reactions to inhaled anticholinergic agents, long- and short-acting alpha-agonists or sympathomimetic amines
 Active pulmonary rehabilitation
GLOW-5
Aim
Efficacy, safety and tolerability of GB in moderate/severe COPD vs once daily tiotropium
Study type
 Randomized controlled trial (double blind)
Size
 n = 657
Inclusion criteria
GOLD moderate-to-severe COPD
 Males and females ≥40 yrs of age
 Smoking history of ≥10 pack-yrs
 GOLD moderate-to-severe COPD
 Post-bronchodilator FEV1 ≥30 % and <80 % of the predicted Post-broncho-dilator FEV1/FVC <0.70
Exclusion criteria
 Lower RTI prior 6 weeks
 Oxygen for chronic hypoxemia
 Concomitant pulmonary disease
Intervention
 GB n = 327, completed 12 week trial n = 314
Comparator
 Tiotropium n = 320, completed 12 week trial n = 316
QTcF >480 ms
 GB: n = 2 (0.64) %
 Tiotropium: n = 0 (0 %)
QTcF increase 30–60 ms:
 GB: n = 11 (3.4 %)
 Tiotropium: n = 10 (3 %)
  Pulmonary tuberculosis
  Bronchiectasis
  History of asthma
  Malignancy of any system
 Long QT syndrome QTc > 450 ms for males or > 470 ms for females,
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow-angle glaucoma
 Alpha-1 anti- trypsin deficiency
 Adverse reactions to inhaled anticholinergic agents, long- and short-acting alpha-agonists or sympathomimetic amines
 Active pulmonary rehabilitation
GLOW-6
Aim
Efficacy, safety and tolerability of GB and indacaterol vs indacaterol alone in moderate/severe COPD
Study type
 Randomized controlled trial (double blind)
Size
 n = 449
Inclusion criteria
 GOLD moderate-to-severe COPD
 Males and females ≥ 40 yrs of age
 Smoking history of ≥ 10 pack-yrs
 GOLD moderate-to-severe COPD
 Post-bronchodilator FEV1 ≥ 30 % and < 80 % of the predicted Post-broncho-dilator FEV1/FVC < 0.70
Exclusion criteria
 Lower RTI prior 6 weeks
 Oxygen for chronic hypoxemia
 Concomitant pulmonary disease
Intervention
 GB + Indacaterol n = 226
Completed 12 week trial n = 212
Comparator
 Indacaterol n = 223 completed 12 week trial n = 210
QTcF >500 ms:
 GB +Ind: n = 0 (0 %)
 Ind: n = 0 (0 %)
QTcF increase 30–60 ms:
 GB + Ind: n = 14 (6.5 %)
 Ind: n = 9 (4.2 %)
  Pulmonary tuberculosis
  Bronchiectasis
  History of asthma
  Malignancy of any system
 Long QT syndrome QTc > 450 ms for males or > 470 ms for females,
 Symptomatic prostatic hyperplasia
 Bladder-neck obstruction
 Moderate/severe renal impairment
 Urinary retention
 Narrow-angle glaucoma
 Alpha-1 anti- trypsin deficiency
 Adverse reactions to inhaled anticholinergic agents, long- and short-acting alpha-agonists or sympathomimetic amines
 Active pulmonary rehabilitation
 Atrial fibrillation
 NYHA III or IV symptoms
  1. FEV 1 forced expiratory volume in 1 second, FVC forced vital capacity, RTI respiratory tract infection