Effect of SGRQ-Defined Chronic Bronchitis at Baseline on Treatment Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate

Figures & data

Table 1 Patient Distribution by CB Status at Baseline

Patients, n (%)	Total N=1293	Placebo N=430	GLY 25 μg BID N=431	GLY 50 μg BID N=432
CB	842 (65.1)	273 (63.5)	281 (65.2)	288 (66.7)
Non-CB	451 (34.9)	157 (36.5)	150 (34.8)	144 (33.3)

Abbreviations: BID, twice daily; CB, chronic bronchitis; GLY, nebulized glycopyrrolate.

Table 2 Baseline Demographics and Disease Characteristics, by CB at Baseline

Parameter	CB			Non-CB
	Placebo N=273	GLY 25 μg BID N=281	GLY 50 μg BID N=288	Placebo N=157	GLY 25 μg BID N=150	GLY 50 μg BID N=144
Age, years, median (range)	63.0 (42–83)	62.0 (40–83)	62.0 (40–85)	68.0 (41–84)	66.0 (42–81)	63.0 (41–87)
Female, n (%)	121 (44.3)	122 (43.4)	113 (39.2)	74 (47.1)	67 (44.7)	72.0 (50.0)
BMI, kg/m^2, median (range)	28.8 (16.3–71.6)	26.9 (14.7–53.4)	27.2 (16.2–55.8)	27.5 (18.3–52.7)	28.2 (16.9–53.1)	27.97 (17.7–51.0)
Current smoker, n (%)	171 (62.6)	188 (66.9)	174 (60.4)	47 (29.9)	52 (34.7)	52 (36.1)
Pack years, median (range)	48.0 (10–240)	45.0 (10–192)	45.5 (10–147)	45.0 (13–129)	47.0 (11–132)	45.5 (10–214)
Background LABA, n (%)	81 (29.7)	85 (30.2)	93 (32.3)	51 (32.5)	50 (33.3)	42 (29.2)
Background ICS, n (%)	77 (28.2)	78 (27.8)	84 (29.2)	50 (31.8)	48 (32.0)	38 (26.4)
COPD exacerbation within past 12 months, n (%)	58 (21.2)	55 (19.6)	48 (16.7)	35 (22.3)	29 (19.3)	25 (17.4)
FEV1 (L), median (range)	1.27 (0.54–3.15)	1.28 (0.48–3.23)	1.28 (0.49–3.14)	1.27 (0.51–2.59)	1.21 (0.57–2.92)	1.23 (0.57–3.26)
Post-bronchodilator FEV1, n (%)
<30% predicted	14 (5.1)	20 (7.1)	26 (9.0)	10 (6.4)	9 (6.0)	9 (6.3)
≥30% predicted and <50% predicted	99 (36.3)	95 (33.8)	99 (34.4)	54 (34.4)	61 (40.9)	59 (41.0)
≥50% predicted	160 (58.6)	166 (59.1)	163 (56.6)	93 (59.2)	79 (53.0)	76 (52.8)
Baseline SGRQ total score, median (range)	52.42 (4.04–98.21)	54.55 (11.54–95.94)	54.44 (7.86–90.25)	38.03 (1.13–84.52)	38.78 (0–80.81)	42.55 (0–86.15)
Activity	72.33 (0–100)	72.33 (0–100)	72.63 (0–100)	60.27 (0–100)	59.46 (0–100)	64.84 (0–100)
Symptoms	70.95 (27.48–100)	74.23 (24.44–100)	72.66 (24.55–97.7)	42.79 (0–89.74)	44.41 (0–85.04)	43.62 (0–91.09)
Impacts	37.4 (0–98.88)	38.61 (1.63–96.83)	38.25 (1.63–85.89)	24.39 (0–83.54)	26.68 (0–79.39)	26.72 (0–81.01)
Baseline EXACT-RS total score, median (range)	14.0 (0–34.71)	14.86 (0.14–32.43)	13.14 (1.6–36.14)	8.0 (0–30.86)	7.93 (0–28.0)	9.43 (0–28.0)
Breathlessness	6.85 (0–15.43)	7.07 (0–15.83)	6.29 (0–16.0)	5.0 (0–15.43)	4.64 (0–15.0)	5.86 (0–14.6)
Cough and sputum	4.14 (0–10.0)	4.43 (0–10.0)	4.14 (0.57–10.0)	1.36 (0–7.0)	1.67 (0–6.71)	1.71 (0–7.71)
Chest symptoms	3.0 (0–9.43)	3.16 (0–9.29)	2.86 (0–10.29)	1.57 (0–10.29)	1.08 (0–8.57)	1.20 (0–8.0)

Abbreviations: BID, twice daily; BMI, body mass index; CB, chronic bronchitis; COPD, chronic obstructive pulmonary disease; EXACT-RS, EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; GLY, glycopyrrolate; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; SGRQ, St George’s Respiratory Questionnaire.

Figure 1 Pooled analysis of (A) trough FEV₁ (mL) at 12 Weeks by CB at baseline, and (B) change from baseline in FEV₁ (mL) with time in the CB and (C) non-CB groups with GLY 25 μg BID and placebo (ITT population). **p<0.01; ****p<0.0001 for GLY 25 μg BID vs placebo.

Note: The n values represent the number of patients who have on-treatment change from baseline in trough FEV₁ data at the corresponding treatment week.

Abbreviations: BID, twice daily; CB, chronic bronchitis; FEV₁, forced expiratory volume in 1 second; GLY, nebulized glycopyrrolate; ITT, intent-to-treat; LS, least squares; SE, standard error.

Figure 2 Pooled analysis of (A) SGRQ total scores and (B) responder rates at 12 weeks with GLY 25 μg BID and placebo, by baseline CB status. *p<0.05; ***p<0.001 for GLY 25 μg BID vs placebo.

Note: The n values represent the number of patients who have on-treatment change from baseline in SGRQ scores at Week 12.

Abbreviations: BID, twice daily; CI, confidence interval; CB, chronic bronchitis; GLY, nebulized glycopyrrolate; LS, least squares; OR, odds ratio; SE, standard error; SGRQ, St George’s respiratory questionnaire.

Figure 3 Pooled analysis of placebo-adjusted change from baseline in EXACT-RS total and domain scores at 12 weeks with GLY 25 μg BID, by CB group (ITT population). *p<0.05 for GLY 25 μg BID vs placebo.

Note: The n values represent the number of patients with on-treatment change from baseline in EXACT-RS scores at Week 12.

Abbreviations: BID, twice daily; CB, chronic bronchitis; EXACT-RS, EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms; GLY, nebulized glycopyrrolate; ITT, intent-to-treat; LS, least squares; SE, standard error.

Table 3 Summary of AEs, SAEs, and AEs Leading to Treatment Discontinuation, Including Individual AEs with Incidence ≥3% with Placebo or GLY 25 μg BID, by Baseline CB Status (Safety Population)

Preferred Term, n (%)	CB		Non-CB
	Placebo N=273	GLY 25 µg BID N=281	Placebo N=157	GLY 25 µg BID N=150
Any AE	139 (50.9)	119 (42.3)	86 (54.8)	68 (45.3)
Worsening of COPD	26 (9.5)	19 (6.8)	11 (7.0)	9 (6.0)
Cough	18 (6.6)	20 (7.1)	18 (11.5)	10 (6.7)
Dyspnea	9 (3.3)	15 (5.3)	4 (2.5)	6 (4.0)
Wheezing	2 (0.7)	1 (0.4)	3 (1.9)	5 (3.3)
Any SAE	16 (5.9)	9 (3.2)	8 (5.1)	4 (2.7)
AEs leading to study treatment withdrawal	21 (7.7)	14 (5.0)	19 (12.1)	8 (5.3)

Abbreviations: AE, adverse event; BID, twice daily; CB, chronic bronchitis; COPD, chronic obstructive pulmonary disease; GLY, glycopyrrolate; SAE, serious adverse event.