Bronchodilator efficacy of 18 μg once-daily tiotropium inhalation via Discair^® versus HandiHaler^® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial

Figures & data

Table 1 Baseline characteristics of COPD patients in the reference group (HandiHaler^®) and test group (Discair^®)

	Reference (n=29)	Test (n=29)
Age (years)
Mean (SD)	61.7 (6.4)	62.5 (8.2)
Sex, male/female
N	29/0	29/0
Body mass index (kg/m^2), mean (SD)	27.0 (4.1)	25.8 (4.7)
Smoking status
Ex-smoker, n (%)	24 (82.8)	18 (62.1)
Active smoker, n (%)	5 (17.2)	11 (37.9)
Smoking (pack/year), mean (SD)	51.5 (37.7)	67.4 (30.1)
Onset of COPD
Newly diagnosed, n (%)	3 (10.3)	4 (13.8)
Formerly diagnosed, n (%)	26 (89.7)	25 (86.2)
Duration of COPD (years)
Mean (SD)	3.5 (3.7)	3.6 (4.6)
GOLD category, n (%)
B	25 (86.2)	25 (86.2)
C	0 (0.0)	1 (3.5)
D	4 (13.8)	3 (10.3)
mMRC score, n (%)
1	8 (27.6)	5 (17.2)
2	20 (69.0)	21 (72.4)
3	1 (3.4)	3 (10.3)
Exacerbations in the last year, n (%)
None	18 (62.1)	17 (58.6)
1	5 (17.2)	4 (13.8)
2	5 (17.2)	8 (27.6)
3	1 (3.5)	0 (0.0)
Use of COPD medication, n (%)
Yes	24 (82.8)	24 (82.8)
No	5 (17.2)	5 (17.2)
Vital signs, mean (SD)
Pulse (bpm)	75.4 (7.8)	77.8 (7.8)
Body temperature (°C)	36.3 (0.6)	36.3 (0.4)
Arterial blood pressure (mmHg)	125.1 (14.4)	124.8 (19.3)
Venous blood pressure (mmHg)	76.2 (10.8)	74.2 (9.8)
Respiratory rate (breaths/min)	20.2 (2.2)	20.8 (2.1)
CBC, mean (SD)
Hemoglobin (g/dL)	14.5 (1.0)	14.7 (1.2)
Hematocrit (%)	43.7 (2.6)	44.0 (3.9)
WBC (×10^9/L)	8.6 (2.2)	8.3 (1.9)
Platelet (×10^9/L)	238.7 (63.0)	244.4 (78.1)

Abbreviations: CBC, complete blood count; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Obstructive Lung Disease; mMRC, modified Medical Research Council; SD, standard deviation; WBC, white blood cell.

Table 2 Spirometry findings before (0 h) and 24 h after bronchodilator use in the reference group (HandiHaler^®) and test group (Discair^®)

	FEV1, L (SD)			FVC, L (SD)
	Reference (n=29)	Test (n=29)	P-valuea	Reference (n=29)	Test (n=29)	P-valuea
Pre-bronchodilator	1.39 (0.40)	1.36 (0.38)	0.764	2.33 (0.48)	2.20 (0.46)	0.276
Post-bronchodilator	1.46 (0.43)	1.42 (0.37)	0.708	2.36 (0.52)	2.28 (0.44)	0.546

Note:

a Student’s t-test.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SD, standard deviation.

Table 3 Bronchodilator efficacy parameters in the reference group (HandiHaler^®) and test group (Discair^®)

Efficacy parameters	FEV1			FVC
	Reference (n=29)	Test (n=29)	P-valuea	Reference (n=29)	Test (n=29)	P-valuea
Average change from baseline (h), L (SD)
2	0.18 (0.13)	0.18 (0.15)	0.985	0.29 (0.26)	0.20 (0.20)	0.133
4	0.19 (0.15)	0.20 (0.17)	0.790	0.29 (0.30)	0.24 (0.22)	0.419
8	0.15 (0.14)	0.17 (0.16)	0.520	0.23 (0.26)	0.18 (0.23)	0.413
24	0.05 (0.14)	0.06 (0.13)	0.853	0.11 (0.22)	0.04 (0.16)	0.155
Maximum change from baseline, L (SD)
Mean (SD)	0.2783 (0.1454)	0.2766 (0.1565)	–*	0.4438 (0.2614)	0.3417 (0.2192)	0.113
% change from baseline
Mean (SD)	20.783 (11.202)	22.235 (13.792)	0.662	20.337 (12.139)	16.719 (11.896)	0.257
Area under the response–time curve (h), mean (SD)
0–24	2.8326 (3.2035)	2.9489 (3.2244)	0.891	4.7291 (5.5265)	2.8965 (4.6768)	0.178
0–2	0.2888 (0.1981)	0.2684 (0.2122)	0.268	0.4362 (0.3418)	0.2970 (0.3261)	0.148
0–4	0.6509 (0.4781)	0.6413 (0.5095)	0.941	1.0219 (0.8518)	0.7165 (0.7206)	0.146
0–8	1.3037 (1.0011)	1.3792 (1.1261)	0.788	2.0388 (1.8152)	1.4896 (1.5776)	0.224
Time to onset of response (h), n (%)
0.25	24 (82.8)	26 (89.7)	0.706b	21 (72.4)	24 (82.8)	0.530b
0.5	4 (13.8)	3 (10.3)		4 (13.8)	3 (10.3)
1	0 (0.0)	0 (0.0)	–	3 (10.3)	0 (0.0)
2	0 (0.0)	0 (0.0)	–	0 (0.0)	2 (6.9)
3	0 (0.0)	0 (0.0)	–	1 (3.5)	0 (0.0)
Time to peak response (h), tmax
Mean (SD)	4.1724 (4.9390)	4.6466 (5.9625)	0.743	4.6897 (6.0815)	4.2672 (3.4362)	0.746

Notes:

a Student’s t-test.

b Fisher’s exact test (0.25 vs >0.25).

* The difference of the average maximum change from baseline (0.0017 L [95% CI: −0.0777, 0.0812]) showed that the test inhaler is non-inferior to the reference inhaler. –, Not applicable.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SD, standard deviation.

Figure 1 Maximum change in forced expiratory volume in 1 second (FEV₁, top) and forced vital capacity (FVC, bottom) from baseline (pretreatment, 0 h) to 24 h after bronchodilator treatment in the reference group (HandiHaler^®) and the test group (Discair^®).