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Table 2 Key results from indacaterol studies with a tiotropium comparator arm and double-blind studies with tiotropium as the primary treatment of interest

From: Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium

Study

Design

Patient characteristics

Time

Trough FEV1versus placebo (mL)

Proportion of patients achieving MCID

     

SGRQ (%)

TDI (%)

Indacaterol versus tiotropium studies

INHANCE [9]

OL*

FEV1 <80% and ≥30% predicted; FEV1/FVC <0.7; Mean FEV1 % predicted¶: Indacaterol 150 μg 56.1, Indacaterol 300 μg 56.3, Tiotropium 53.9, Placebo 56.1

12 wk

Tiotropium: 140

44.9†

55.0†

Indacaterol 150 μg: 180

51.9†

58.9†

Indacaterol 300 μg: 180

50.1†

65.8†

   

26 wk

Tiotropium: 140

47.3

57.3

Indacaterol 150 μg: 160

57.8

62.4

Indacaterol 300 μg: 180

52.5

70.8

INTIME [10]

TPB

FEV1 <80 and ≥30% predicted; FEV1/FVC <0.7; Mean FEV1 % predicted¶ 56.7

2 wk

Tiotropium: 120

—

—

Indacaterol 150 μg: 170

—

—

Indacaterol 300 μg: 150

—

—

INTENSITY [11]

B

FEV1 <80 and ≥30% predicted; FEV1/FVC <0.7; Mean FEV1 % predicted¶: Indacaterol 54.6, Tiotropium 54.3

12 wk

Tiotropium: —

42.5

50.1

Indacaterol 150 μg

50.5

57.9

Tiotropium versus placebo studies

Beeh et al. 2006 [15]

DB

FEV1 ≤70% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Total 45.4, Tiotropium 45.3, Placebo 45.7

12 wk

79

—

—

Freeman et al. 2007 [16]

DB

FEV1 30–65% predicted; FEV1/FVC <0.7§; Mean FEV1 % predicted‡: Total 48.9, Tiotropium 47.9, Placebo 49.9

12 wk

60

—

—

Johansson et al. 2008 [17]

DB

FEV1 >60% predicted; FEV1/FVC <0.7¶; Mean FEV1 % predicted§: Tiotropium 73.6, Placebo 73.2

12 wk

118

—

—

Moita et al. 2008 [18]

DB

FEV1 ≤70% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Tiotropium: non-smokers 38.4, smokers 44.4; Placebo: non-smokers 42.3, smokers 40.4

12 wk

102

—

—

Verkindre et al. 2006 [19]

DB

FEV1 ≤50% predicted; FEV1/SVC ≤0.7; lung hyperinflation‡; Mean FEV1 % predicted‡: Tiotropium 34.7, Placebo 35.8

12 wk

110

59

—

Niewoehner et al. 2005 [20]

DB

FEV1 ≤60% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Tiotropium 35.6, Placebo 35.6

13 wk

100

—

—

   

26 wk

100

—

—

Brusasco et al. 2003 [21]

DB

FEV1 ≤65% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Tiotropium 39.2, Placebo 38.7

26 wk

120

48.9

43.1

Tonnel et al. 2008 [22]

DB

FEV1 20–70% predicted; FEV1/FVC 0.7#; Mean FEV1 % predicted‡: Tiotropium 47.5, Placebo 46.2

12 wk

—

60||

—

   

26 wk

—

60||

—

   

39 wk

100

59.1

—

Chan et al. 2007 [23]

DB

FEV1 ≤65% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Tiotropium 39.4, Placebo 39.3

11 wk

100||

—

—

   

48 wk

100

53

—

Casaburi et al. 2002 [24]

DB

FEV1 ≤65% predicted; FEV1/FVC <0.7‡; Mean FEV1 % predicted‡: Tiotropium 39.1, Placebo 38.1

13 wk

148||

—

42–47≈

   

25 wk

148||

—

42–47≈

   

1 yr

150||

49

47≈

Tashkin et al. 2008 [25]

DB

FEV1 ≤70% predicted; FEV1/FVC <0.7¶; Mean FEV1 % predicted¶: Tiotropium 47.7, Placebo 47.4

26 wk

100||

—

—

   

4 yr

87–103

45%

—

  1. Data are least square mean for INHANCE, INTIME and INTENSITY; other publications did not describe the type of mean.
  2. *Tiotropium arm (indacaterol and placebo were DB).
  3. †Data on file at Novartis.
  4. ‡Not stated whether pre- or post-bronchodilator.
  5. §Pre-bronchodilator.
  6. S¶Post-bronchodilator.
  7. #Pre- and post-bronchodilator.
  8. ||Estimated from a figure.
  9. ≈Values are given as 42–47% across all timepoints up to 2 years (greatest improvement versus baseline was seen at 2 years).
  10. Definitions of trough FEV1 varied (mean of 23 hours 10 minutes and 23 hours 45 minutes post-dose for INHANCE, INTIME and INTENSITY, Beeh et al. 2006 [15], Verkindre et al. 2006 [19] and Brusasco et al. 2003 [21]; 10 minutes pre-dose for Freeman et al. 2007 [16], Johansson et al. 2008 [17] and Chan et al. 2007 [23]; 30 minutes pre-dose for Tonnel et al. 2008 [22]; 1 hour pre-dose for Casaburi et al. 2002 [24]; and ‘pre-dose’ for Niewoehner et al. 2005 [20] and Tashkin et al. 2008 [25]. All studies recruited patients aged ≥40 years with a smoking history of ≥10 pack-years (≥20 years for INHANCE).
  11. MCID: minimum clinically important difference; SGRQ: St. George’s Respiratory Questionnaire; TDI: transition dyspnoea index; OL: open-label; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; TPB: third-party blinding; B: blinded; DB: double-blind; SVC: slow vital capacity.
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Respiratory Research

ISSN: 1465-993X

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