Clinically Important Deterioration Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Treated with Nebulized Glycopyrrolate: A Post Hoc Analysis of Pooled Data from Two Randomized, Double-Blind, Placebo-Controlled Studies

Figures & data

Figure 1 GOLDEN 3 and GOLDEN 4 study design.

Notes: ^aFlexible, between 1 and 7 days. ^bContacted by telephone 5 to 7 days after the last study visit.
Abbreviations: CV, cardiovascular; GOLDEN, Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer; LABA, long-acting beta agonist.

Table 1 Baseline Demographic and Clinical Characteristics of the Pooled GOLDEN 3 and GOLDEN 4 ITT Study Cohorts

Characteristics^a	Placebo BID	GLY 25 mcg BID	GLY 50 mcg BID
Patients, n	430	431	432
Age, mean (SD)	63.7 (8.8)	63.3 (8.7)	62.6 (8.6)
Female, n (%)	195 (45.3)	189 (43.9)	185 (42.8)
Race, n (%)
Caucasian	388 (90.2)	385 (89.3)	386 (89.4)
Black or African American	39 (9.1)	42 (9.7)	44 (10.2)
Smoking status, n (%)
Current	218 (50.7)	240 (55.7)	226 (52.3)
Former	212 (49.3)	191 (44.3)	206 (47.7)
High cardiovascular risk: Yes, n (%)^b	278 (64.7)	275 (63.8)	275 (63.7)
LABA use: Yes, n (%)^c	132 (30.7)	135 (31.3)	135 (31.3)
ICS use: Yes, n (%)	127 (29.5)	126 (29.2)	122 (28.2)
Had a COPD exacerbation in the past 12 months: Yes, n (%)^d	93 (21.6)	84 (19.5)	73 (16.9)
Post-bronchodilator FEV1, L, mean (SD)	1.521 (0.5)	1.514 (0.5)	1.533 (0.5)
Post-bronchodilator FEV1, n (%)
<30% predicted (GOLD 4)	24 (5.6)	29 (6.7)	35 (8.1)
≥30% to <50% predicted (GOLD 3)	153 (35.6)	156 (36.2)	158 (36.6)
≥50% to <80% predicted (GOLD 2)	253 (58.8)	245 (56.8)	239 (55.3)
Total SGRQ score, mean (SD)	48.0 (17.5)	49.2 (18.7)	49.2 (18.5)
Completed study, n (%)	379 (88.1)	396 (91.9)	400 (92.6)

Notes: ^aBaseline data were collected in Week 0 (Visit 2). ^bDefined as a clinical diagnosis of one or more of the following conditions: hypertension, ischemic heart disease, cerebrovascular disease, peripheral arterial disease, clinically significant arrhythmia, or heart failure. ^cLimited by protocol to approximately 30%. ^dCOPD exacerbation or worsening, defined as an increase in clinician-assessed COPD symptoms (eg, dyspnea, cough, sputum volume, or sputum purulence) during ≥2 consecutive days, and classified as mild (self-managed, with increased short-acting bronchodilator and/or ICS use), moderate (treated with antibiotics and/or systemic corticosteroids) or severe (requiring hospitalization). Any event occurring within 30 days of a prior event was considered a continuation of the index event.

Abbreviations: BID, twice daily; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second; GLY, glycopyrrolate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GOLDEN, Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer; ICS, inhaled corticosteroids; ITT, intent-to-treat; LABA, long-acting beta-agonist; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire.

Table 2 Proportions of Subjects Meeting Criteria for CID at Treatment Week 12

CID Criteria	Placebo BID		GLY
			25 mcg BID		50 mcg BID
	CID n/Total N	CID, %	CID n/Total N	CID, %	CID n/Total N	CID, %
Any CID endpoint	200/391	51.2%	136/398	34.2%	152/402	37.8%
≥100-mL decrease in baseline post-bronchodilator trough FEV1	88/380	23.2%	48/393	12.2%	56/399	14.0%
≥4-unit increase in SGRQ total score	115/357	32.2%	72/368	19.6%	92/373	24.7%
HCRU-related moderate or severe exacerbation^a	40/430	9.3%	33/431	7.7%	39/432	9.0%

Notes: ^aDefined as an increase in clinician-assessed COPD symptoms (eg, dyspnea, cough, sputum volume, or sputum purulence) during at least two consecutive days, and classified as “moderate” (treated with clinic visit with or without antibiotics or oral corticosteroids but no hospitalization) or “severe” (requiring overnight stay in a hospital or emergency room).

Abbreviations: BID, twice daily; CID, clinically important deterioration; FEV₁, forced expiratory volume in one second; GLY, glycopyrrolate; HCRU, healthcare resource utilization; LABA, long-acting beta-agonist; SGRQ, St. George’s Respiratory Questionnaire.

Figure 2 Risk (adjusted odds ratio)^a of CID at week 12 of treatment with GLY (25 mcg BID and 50 mcg BID) compared to placebo.

Notes: ^aOdds ratio (GLY/placebo), adjusted for high cardiovascular risk, LABA use, baseline FEV1, baseline SGRQ total score, and 12-month prior history of exacerbations. ^bDefined as an increase in clinician-assessed COPD symptoms (eg, dyspnea, cough, sputum volume, or sputum purulence) during at least two consecutive days, and classified as “moderate“ (treated with clinic visit, but no hospitalization, with or without antibiotics or oral corticosteroids) or “severe“ (requiring overnight stay in a hospital or emergency room). *p<0.05.
Abbreviations: BID, twice daily; CI, confidence interval; CID, clinically important deterioration; FEV₁, forced expiratory volume in one second; GLY, glycopyrrolate; HCRU, healthcare resource utilization; LABA, long-acting beta-agonist; OR, odds ratio; SGRQ, St. George’s Respiratory Questionnaire.

Figure 3 Subgroup analysis of the risk (adjusted odds ratio)^a of CID at week 12 of treatment with GLY 25 mcg BID compared to placebo.

Notes: ^aOdds ratio (GLY/placebo), adjusted for high cardiovascular risk, LABA use, baseline FEV1, baseline SGRQ total score, and 12-month prior history of exacerbations. *p<0.05.
Abbreviations: BID, twice daily; CI, confidence interval; CID, clinically important deterioration; FEV₁, forced expiratory volume in one second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GLY, glycopyrrolate; LABA, long-acting beta-agonist; OR, odds ratio; PIFR, peak inspiratory flow rate.

Figure 4 Subgroup analysis of the risk (adjusted odds ratio)^a of CID at week 12 of treatment with GLY 50 mcg BID compared to placebo BID.

Notes: ^aOdds ratio (GLY/placebo), adjusted for high cardiovascular risk, LABA use, baseline FEV1, baseline SGRQ total score, and 12-month prior history of exacerbations. *p<0.05.
Abbreviations: BID, twice daily; CI, confidence interval; CID, clinically important deterioration; FEV₁, forced expiratory volume in one second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GLY, glycopyrrolate; LABA, long-acting beta-agonist; OR, odds ratio; PIFR, peak inspiratory flow rate.