The IMPACT Study – Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI And UMEC/VI In Patients With COPD: Efficacy And Safety In A Japanese Population

Figures & data

Table 1 Patient Demographics And Baseline Characteristics In The Japan Subgroup And Overall Study Population (ITT population)

Characteristic	Japan			Overall
	FF/UMEC/VI n=149	FF/VI n=149	UMEC/VI n=80	FF/UMEC/ I n=4151	FF/VI n=4134	UMEC/VI n=2070
Male, n (%)	139 (93)	140 (94)	72 (90)	2766 (67)	2748 (66)	1356 (66)
Age, years, mean (SD)	70.7 (7.3)	70.1 (7.2)	71.1 (6.8)	65.3 (8.2)	65.3 (8.3)	65.2 (8.3)
<65 years, n (%)	22 (15)	32 (21)	14 (18)	1886 (45)	1876 (45)	962 (46)
≥65 years, n (%)	127 (85)	117 (79)	66 (83)	2265 (55)	2258 (55)	1108 (54)
BMI, kg/m^2, mean (SD)	21.6 (3.3)	22.2 (3.4)	22.8 (3.7)	26.6 (6.2)	26.7 (6.1)	26.6 (5.9)
≤21 kg/m^2, n (%)	63 (42)	57 (38)	26 (33)	739 (18)	697 (17)	340 (16)
<25 kg/m^2, n (%)	128 (86)	114 (77)	61 (76)	1856 (45)	1768 (43)	902 (44)
Smoking status, n (%)
Current smoker	40 (27)	37 (25)	14 (18)	1436 (35)	1423 (34)	728 (35)
Former smoker	109 (73)	112 (75)	66 (83)	2715 (65)	2711 (66)	1342 (65)
Moderate/severe COPD exacerbations in previous 12 months, n (%)
<2 moderate and 0 severe	37 (25)	41 (28)	20 (25)	1198 (29)	1242 (30)	616 (30)
≥2 moderate or ≥1 severe	112 (75)	108 (72)	60 (75)	2953 (71)	2892 (70)	1454 (70)
Reversible to salbutamol,^a n (%)	17 (11)	8 (5)	1 (1)	734 (18)	810 (20)	366 (18)
Post-bronchodilator FEV1, % predicted normal, mean (SD)	50.7 (15.7)	51.3 (16.0)	47.3 (14.8)	45.7 (15.0)	45.5 (14.8)	45.4 (14.7)
Post-bronchodilator FEV1, L, mean (SD)	1.247 (0.429)	1.287 (0.435)	1.140 (0.384)	1.275 (0.488)	1.272 (0.486)	1.268 (0.481)
Pre-bronchodilator FEV1, % predicted normal, mean (SD)	47.6 (15.5)	48.1 (15.7)	44.9 (14.9)	41.9 (14.6)	41.6 (14.5)	41.8 (14.4)
Pre-bronchodilator FEV1, L, mean (SD)	1.171 (0.419)	1.207 (0.424)	1.086 (0.395)	1.170 (0.468)	1.163 (0.468)	1.167 (0.464)
GOLD grade, n (%)
1 (mild: FEV1% predicted ≥80%)	1 (<1)	0	0	10 (<1)	8 (<1)	4 (<1)
2 (moderate: 50%≤ FEV1% predicted <80%)	73 (49)	65 (44)	27 (34)	1535 (37)	1455 (35)	729 (35)
3 (severe: 30%≤ FEV1% predicted <50%)	60 (40)	72 (48)	43 (54)	1934 (47)	2031 (49)	1017 (49)
4 (very severe: FEV1% predicted <30%)	15 (10)	12 (8)	10 (13)	666 (16)	639 (15)	319 (15)
CAT score, mean (SD)	14.6 (5.8)	14.9 (7.3)	15.4 (6.9)	18.2 (7.0)	18.3 (7.0)	18.1 (6.9)
SGRQ total score, mean (SD)	39.6 (14.2)	39.8 (16.1)	42.8 (15.4)	50.8 (16.8)	50.7 (17.0)	50.2 (16.7)
COPD medication, n (%)
ICS+LABA+LAMA	38 (26)	39 (26)	30 (38)	1396 (34)	1433 (35)	734 (35)
ICS+LABA	16 (11)	13 (9)	7 (9)	1103 (27)	1067 (26)	523 (25)
LABA+LAMA	37 (25)	31 (21)	17 (21)	330 (8)	308 (7)	163 (8)
LAMA	24 (16)	32 (21)	9 (11)	273 (7)	331 (8)	140 (7)
History of pneumonia, n (%)	47 (32)	57 (38)	34 (43)	916 (22)	951 (23)	476 (23)
Blood eosinophil count, n (%)
<150 cells/µL	76 (51)	71 (48)	38 (48)	1844 (45)	1769 (43)	869 (42)
<300 cells/µL	123 (83)	124 (83)	58 (72)	3280 (79)	3212 (78)	1597 (77)
≥150 cells/µL	73 (49)	78 (52)	42 (52)	2299 (55)	2356 (57)	1196 (58)
≥300 cells/µL	26 (17)	25 (17)	22 (28)	863 (21)	913 (22)	468 (23)

Notes: Values are at screening, unless stated otherwise. ^aReversibility was defined as an increase in FEV₁ ≥12% and ≥200 mL following administration of salbutamol.

Abbreviations: BMI, body mass index; CAT, chronic obstructive pulmonary disease Assessment Test; ; FF, fluticasone furoate; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting β₂-adrenergic antagonist; LAMA, long-acting muscarinic antagonist; SGRQ, St. George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Figure 1 On-treatment moderate/severe exacerbations in the Japan subgroup and overall study population with FF/UMEC/VI versus dual therapies (ITT populations).

Note: *p<0.001.
Abbreviations: FF, fluticasone furoate; ITT, intent-to-treat; UMEC, umeclidinium; VI, vilanterol.

Figure 2 Time-to-first on-treatment moderate/severe exacerbation in the Japan subgroup and overall study population with FF/UMEC/VI versus dual therapies (ITT populations).

Notes: *Probability of having an event (prior to Day 365) is taken from the Kaplan–Meier estimates; ^†p<0.001.
Abbreviations: FF, fluticasone furoate; ITT, intent-to-treat; UMEC, umeclidinium; VI, vilanterol.

Figure 3 Change from baseline at Week 52 in (A) trough FEV₁ and (B) post-bronchodilator FEV₁ in the Japan subgroup and overall study population with FF/UMEC/VI versus dual therapies (ITT populations).

Note: *p<0.001.
Abbreviations: FF, fluticasone furoate; ITT, intent-to-treat; LS, least squares; UMEC, umeclidinium; VI, vilanterol.

Figure 4 Change from baseline at Week 52 in (A) SGRQ total score and (B) CAT score in the Japan subgroup and overall study population with FF/UMEC/VI versus dual therapies (ITT populations).

Notes: *p<0.001; **p=0.021.
Abbreviations: CAT, Chronic obstructive pulmonary disease Assessment Test; FF, fluticasone furoate; ITT, intention to treat; LS, least squares; SGRQ, St. George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Table 2 Safety Summary In Japan Subgroup And Overall Study Population (ITT populations)

AE incidence, n (%)	Japan			Overall
	FF/UMEC/VI n=149	FF/VI n=149	UMEC/VI n=80	FF/UMEC/VI n=4151	FF/VI n=4134	UMEC/VI n=2070
Any on-treatment AE	117 (79)	116 (78)	61 (76)	2897 (70)	2800 (68)	1429 (69)
Any on-treatment drug-related AE^a	19 (13)	19 (13)	7 (9)	478 (12)	492 (12)	214 (10)
On-treatment AESI
Anticholinergic syndrome (SMQ)	8 (5)	4 (3)	3 (4)	184 (4)	140 (3)	70 (3)
Asthma/bronchospasm (SMQ)	0 (0)	0 (0)	2 (3)	27 (<1)	34 (<1)	16 (<1)
Cardiovascular effects	10 (7)	11 (7)	8 (10)	450 (11)	430 (10)	224 (11)
Decreased BMD and associated fractures	6 (4)	2 (1)	1 (1)	98 (2)	85 (2)	37 (2)
Effects on potassium	1 (<1)	3 (2)	0 (0)	34 (<1)	25 (<1)	8 (<1)
Gastrointestinal obstruction (SMQ)	0 (0)	1 (<1)	0 (0)	9 (<1)	10 (<1)	2 (<1)
Hyperglycemia/new onset diabetes mellitus (SMQ)	6 (4)	4 (3)	5 (6)	152 (4)	117 (3)	73 (4)
Hypersensitivity	13 (9)	14 (9)	9 (11)	196 (5)	195 (5)	95 (5)
LRTI excluding pneumonia	13 (9)	12 (8)	7 (9)	200 (5)	199 (5)	108 (5)
Local steroid effects	15 (10)	10 (7)	6 (8)	337 (8)	301 (7)	108 (5)
Ocular effects	1 (<1)	3 (2)	1 (1)	55 (1)	45 (1)	26 (1)
Pneumonia	27 (18)	31 (21)	4 (5)	317 (8)	292 (7)	97 (5)
Any on-treatment SAE	35 (23)	44 (30)	17 (21)	895 (22)	850 (21)	470 (23)
Any on-treatment drug-related SAE^a	4 (3)	6 (4)	0 (0)	64 (2)	57 (1)	27 (1)
Any on-treatment fatal SAE	2 (1)	1 (<1)	0 (0)	68 (2)	76 (2)	49 (2)
On-treatment SAE occurring in >1% of patients in any treatment arm
COPD	15 (10)	18 (12)	10 (13)	443 (11)	450 (11)	269 (13)
Pneumonia	15 (10)	17 (11)	0 (0)	184 (4)	152 (4)	54 (3)
Pneumonia bacterial	1 (<1)	4 (3)	0 (0)	2 (<1)	9 (<1)	0 (0)
Cardiac failure congestive	0 (0)	1 (<1)	2 (3)	21 (<1)	12 (<1)	7 (<1)
Adjudicated on-treatment pneumonia-related SAEs^b
COPD exacerbation with evidence of pneumonia	9 (6)	8 (5)	6 (8)	123 (3)	129 (3)	57 (3)
Pneumonia/RTI without COPD exacerbation	7 (5)	9 (6)	0 (0)	63 (2)	59 (1)	21 (1)

Notes: ^aIn the opinion of the investigator; ^bAdjudication performed by an independent adjudication committee (only the primary event in the SAE report was adjudicated).

Abbreviations: AE, adverse event; BMD, bone mineral density; FF, fluticasone furoate; ITT, intent-to-treat; LRTI, lower respiratory tract infection; RTI, respiratory tract infection; SAE, serious adverse event; SMQ, Standardized MedDRA (Medical Dictionary for Regulatory Activities) query; UMEC, umeclidinium; VI, vilanterol.

Data Availability

Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.