Table 1 Summary Table of the glycopyrronium QTCF effects in the GLOW 1–6 trials (the GB in COPD airWays studies)[4–9]
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 |