Efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: effect of baseline disease severity and age; pooled analysis of GOLDEN 3 and GOLDEN 4

Figures & data

Figure 1 GOLDEN 3 and GOLDEN 4 study designs: 12-week, randomized, double-blind, placebo-controlled, parallel group, multicenter, efficacy and safety studies.

Notes: Data from Kerwin et al.¹⁹
Abbreviations: BID, twice daily; CS, closed system; ICS, inhaled corticosteroid; LABA, long-acting beta₂-agonist.

Table 1 Patient demographics by post-bronchodilator baseline FEV₁% predicted (ITT population)

FEV1% predicted	Placebo		GLY 25 μg BID		GLY 50 μg BID
	<50% (N=177)	≥50% (N=253)	<50% (N=185)	≥50% (N=245)	<50% (N=193)	≥50% (N=239)
Baseline FEV1, median (range), L	0.930 (0.510–2.045)	1.520 (0.710–3.145)	0.965 (0.475–2.220)	1.493 (0.605–3.225)	0.940 (0.490–2.205)	1.595 (0.690–3.260)
High CV risk	113 (63.8)	165 (65.2)	122 (65.9)	153 (62.4)	119 (61.7)	156 (65.3)
Background LABA use	70 (39.5)	62 (24.5)	74 (40.0)	60 (24.5)	77 (39.9)	58 (24.3)
Age
<65 years	87 (49.2)	133 (52.6)	91 (49.2)	139 (56.7)	113 (58.5)	141 (59.0)
≥65 years	90 (50.8)	120 (47.4)	94 (50.8)	106 (43.3)	80 (41.5)	98 (41.0)
≥75 yearsa	19 (10.7)	22 (8.7)	17 (9.2)	30 (12.2)	18 (9.3)	20 (8.4)

Notes: Data are presented as N (%) unless otherwise stated.

a Subset of the ≥65 years subgroup.

Abbreviations: ITT, intent-to-treat; GLY, glycopyrrolate inhalation solution; BID, twice daily; CV, cardiovascular; LABA, long-acting beta₂-agonist.

Table 2 Patient demographics by age (ITT population)

Age, years	Placebo			GLY 25 μg BID			GLY 50 μg BID
	<65 (N=220)	≥65 (N=210)	≥75a (N=41)	<65 (N=231)	≥65 (N=200)	≥75a (N=47)	<65 (N=254)	≥65 (N=178)	≥75a (N=38)
Baseline FEV1, median (range), L	1.380 (0.545–3.145)	1.190 (0.510–2.435)	1.075 (0.535–2.060)	1.415 (0.530–3.225)	1.130 (0.475–2.760)	1.215 (0.530–1.785)	1.323 (0.490–3.260)	1.165 (0.580–2.645)	1.140 (0.625–2.630)
High CV risk	121 (55.0)	157 (74.8)	36 (87.8)	121 (52.4)	154 (77.0)	34 (72.3)	140 (55.1)	135 (75.8)	30 (78.9)
Background LABA use	50 (22.7)	82 (39.0)	20 (48.8)	66 (28.6)	69 (34.5)	15 (31.9)	74 (29.1)	61 (34.3)	14 (36.8)
Post-bronchodilator FEV1% predictedb
<50%	87 (39.5)	90 (42.9)	19 (46.3)	91 (39.4)	94 (47.0)	17 (36.2)	113 (44.5)	80 (44.9)	18 (47.4)
≥50%	133 (60.5)	120 (57.1)	22 (53.7)	139 (60.2)	106 (53.0)	30 (63.8)	141 (55.5)	98 (55.1)	20 (52.6)

Notes: Data are presented as N (%) unless otherwise stated.

a Subset of the ≥65 years subgroup.

b One post-bronchodilator FEV₁ measurement was missing for a patient aged ≥65 years in the GLY 25 μg BID group.

Abbreviations: ITT, intent-to-treat; GLY, glycopyrrolate inhalation solution; BID, twice daily; CV, cardiovascular; LABA, long-acting beta₂-agonist.

Figure 2 LS mean change from baseline in trough FEV₁ by (A) baseline FEV₁% predicted and (B) age.

Notes: *P<0.05 vs placebo; **P<0.01 vs placebo; ***P<0.001 vs placebo. ^aSubset of the ≥65 years subgroup.
Abbreviations: LS, least squares; SE, standard error; GLY, glycopyrrolate inhalation solution; BID, twice daily.

Figure 3 LS mean SGRQ total score by (A) baseline FEV₁% predicted and (B) age.

Notes: *P<0.05 vs placebo; **P<0.01 vs placebo. ^aSubset of the ≥65 years subgroup.
Abbreviations: LS, least squares; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; GLY, glycopyrrolate inhalation solution; BID, twice daily; MCID, minimum clinically important difference.

Figure 4 SGRQ responder (≥4-unit reduction in SGRQ total score) rates by (A) baseline FEV₁% predicted and (B) age.

Notes: *P<0.05 vs placebo. ^aSubset of the ≥65 years subgroup.
Abbreviations: SGRQ, St George’s Respiratory Questionnaire; GLY, glycopyrrolate inhalation solution; BID, twice daily.

Table 3 TEAEs^ and serious TEAEs by baseline FEV₁% predicted subgroup (safety population)

Preferred term, %	FEV1% predicted <50%			FEV1% predicted ≥50%
	Placebo	GLY		Placebo	GLY
	(N=177)	25 μg BID (N=185)	50 μg BID (N=193)	(N=253)	25 μg BID (N=245)	50 μg BID (N=239)
Any TEAE	49.2	40.0	54.4	54.5	46.1	47.7
Cough	9.6	5.4	8.8	7.5	8.2	9.2
COPD worsening	9.6	7.6	11.4	7.9	5.7	6.3
Dyspnea	4.0	8.1	6.2	2.4	2.4	0.8
Urinary tract infection	1.1	2.2	4.1	1.6	2.0	1.7
Upper respiratory tract infection	1.1	1.1	4.7	0.8	1.6	2.5
Headache	2.8	0.5	1.6	2.0	2.4	2.1
Chest discomfort	2.3	1.1	1.6	2.0	1.2	0.4
Edema peripheral	1.1	1.1	3.1	0.8	0.8	1.3
Arthralgia	0.6	0.5	1.0	1.6	0.8	2.9
Any serious TEAEs	6.8	3.8	5.2	4.7	2.4	3.3

Note:

^ ≥2% incidence in any treatment group in the overall safety population.

Abbreviations: TEAE, treatment-emergent adverse event; GLY, glycopyrrolate inhalation solution; BID, twice daily.

Table 4 TEAEs^ and serious TEAEs by age (safety population)

Preferred term, %	Age <65 years			Age ≥65 years			Age ≥75 yearsa
	Placebo	GLY		Placebo	GLY		Placebo	GLY
	(N=220)	25 μg BID (N=231)	50 μg BID (N=254)	(N=210)	25 μg BID (N=200)	50 μg BID (N=178)	(N=41)	25 μg BID (N=47)	50 μg BID (N=38)
Any TEAEs	51.4	40.7	47.6	53.3	46.5	55.1	46.3	42.6	52.6
Cough	8.2	5.6	8.3	8.6	8.5	10.1	7.3	10.6	5.3
COPD worsening	8.6	7.4	8.7	8.6	5.5	8.4	4.9	4.3	2.6
Dyspnea	2.7	3.5	1.6	3.3	6.5	5.6	0	6.4	2.6
Urinary tract infection	0.9	2.2	2.0	1.9	2.0	3.9	2.4	4.3	0
Upper respiratory tract infection	1.4	0.9	3.9	0.5	2.0	2.8	0	2.1	2.6
Headache	3.2	0.4	1.2	1.4	3.0	2.8	0	6.4	0
Chest discomfort	1.4	1.3	0.8	2.9	1.0	1.1	2.4	0	2.6
Edema peripheral	0.9	0.9	2.8	1.0	1.0	1.1	4.9	0	0
Arthralgia	0.9	0.4	2.0	1.4	1.0	2.2	0	0	0
Any serious TEAEs	4.1	2.6	3.9	7.1	3.5	4.5	7.3	0	5.3

Notes:

^ ≥2% incidence in any treatment group in the overall safety population.

a Subset of the ≥65 years subgroup.

Abbreviations: TEAE, treatment-emergent adverse event; GLY, glycopyrrolate inhalation solution; BID, twice daily.

Table 5 MACE by FEV₁% predicted subgroup (safety population)

MACE category, N (%) [IR]	FEV1% predicted <50%			FEV1% predicted ≥50%
	Placebo	GLY		Placebo	GLY
	(N=177)	25 μg BID (N=185)	50 μg BID (N=193)	(N=253)	25 μg BID (N=245)	50 μg BID (N=239)
MACE	0	0	1 (0.5) [17.1]	2 (0.8) [27.4]	0	2 (0.8) [28.5]
CV death	0	0	1 (0.5) [17.1]	0	0	0
Non-fatal MI	0	0	0	2 (0.8) [27.4]	0	1 (0.4) [14.3]
Non-fatal stroke	0	0	0	0	0	1 (0.4) [14.3]

Abbreviations: MACE, major adverse cardiovascular events; IR, incidence rate per 1,000 patient-years; GLY, glycopyrrolate inhalation solution; BID, twice daily; CV, cardiovascular; MI, myocardial infarction.

Table 6 MACE by age subgroup (safety population)

MACE category, N (%) [IR]	Age <65 years			Age ≥65 years			Age ≥75 yearsa
	Placebo	GLY		Placebo	GLY		Placebo	GLY
	(N=220)	25 μg BID (N=231)	50 μg BID (N=254)	(N=210)	25 μg BID (N=200)	50 μg BID (N=178)	(N=41)	25 μg BID (N=47)	50 μg BID (N=38)
MACE	0	0	2 (0.8) [26.7]	2 (1.0) [33.8]	0	1 (0.6) [18.6]	1 (2.4) [82.0]	0	1 (2.6) [84.7]
CV death	0	0	1 (0.4) [13.4]	0	0	0	0	0	0
Non-fatal MI	0	0	1 (0.4) [13.4]	2 (1.0) [33.8]	0	0	1 (2.4) [82.0]	0	0
Non-fatal stroke	0	0	0	0	0	1 (0.6) [18.6]	0	0	1 (2.6) [84.7]

Note:

a Subset of the ≥65 years subgroup.

Abbreviations: MACE, major adverse cardiovascular events; IR, incidence rate per 1,000 patient-years; GLY, glycopyrrolate inhalation solution; BID, twice daily; CV, cardiovascular; MI, myocardial infarction.

KerwinEDonohueJFGoodinTTosielloRWheelerAFergusonGTEfficacy and safety of glycopyrrolate/eFlow® CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trialsRespir Med201713223825028838685

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