Trial Outcomes & Findings for A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With Asthma (NCT NCT00139659)

Results Overview

Annualized rates of change (slope throughout time from baseline to end of study\[visit\]) for forced expiratory volume in 1 second (FEV1) (liters per year \[L/yr\]) measured 30 minutes following the administration of albuterol.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

288 participants

Primary outcome timeframe

Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52

Results posted on

2010-06-02

Participant Flow

Subjects were recruited at 63 centers and participated in the study between 10 January 2003 and 22 October 2008.

544 subjects were screened for the study. Prior to randomization subjects completed a 3-week run-in period during which all subjects received subcutaneous insulin. Of 288 subjects randomized, only 286 received randomized treatment; one subject assigned to inhaled insulin received subcutaneous insulin, and 1 subject DC'd prior to treatment.

Participant milestones

Participant milestones
Measure	Inhaled Insulin Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Overall Study STARTED	146	141
Overall Study COMPLETED	106	123
Overall Study NOT COMPLETED	40	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Inhaled Insulin Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Overall Study Adverse Event	12	1
Overall Study Lack of Efficacy	1	1
Overall Study Lost to Follow-up	7	3
Overall Study Reason not Specified	6	3
Overall Study Withdrawal by Subject	14	10

Baseline Characteristics

A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inhaled Insulin n=146 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=141 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.	Total n=287 Participants Total of all reporting groups
Age, Customized 18-25 years	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Age, Customized 26-35 years	18 participants n=5 Participants	13 participants n=7 Participants	31 participants n=5 Participants
Age, Customized 36-45 years	23 participants n=5 Participants	25 participants n=7 Participants	48 participants n=5 Participants
Age, Customized 46-55 years	33 participants n=5 Participants	41 participants n=7 Participants	74 participants n=5 Participants
Age, Customized 56-65 years	40 participants n=5 Participants	37 participants n=7 Participants	77 participants n=5 Participants
Age, Customized 66-75 years	20 participants n=5 Participants	17 participants n=7 Participants	37 participants n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	91 Participants n=7 Participants	188 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	50 Participants n=7 Participants	99 Participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52

Population: Primary analysis set (PAS): all subjects who were randomized, had no significant protocol violations, had baseline (BL) post-albuterol pulmonary function test (PFT) measurement, had at least 2 post-BL, post-albuterol PFT measurements with 1 measurement at least 6 months post-BL, and received study drug for at least 50% (154 days) of study duration.

Annualized rates of change (slope throughout time from baseline to end of study\[visit\]) for forced expiratory volume in 1 second (FEV1) (liters per year \[L/yr\]) measured 30 minutes following the administration of albuterol.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=117 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=127 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Annualized Rate of Change for Forced Expiratory Volume in 1 Second (FEV1)	-0.070 L/yr Standard Error 0.020	-0.035 L/yr Standard Error 0.019

PRIMARY outcome

Timeframe: Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52

Population: Primary analysis set (PAS).

Annualized rates of change (slope throughout time from baseline to end of study\[visit\]) for hemoglobin-adjusted carbon monoxide diffusion capacity (DLco)in milliliters per minute/millimeters of mercury/year (ml/min/mmHg/yr) measured 30 minutes following the administration of albuterol.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=117 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=127 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Annualized Rate of Change for Hemoglobin-adjusted Carbon Monoxide Diffusion Capacity (DLco)	-0.776 ml/min/mmHg/yr Standard Error 0.152	-0.273 ml/min/mmHg/yr Standard Error 0.153

PRIMARY outcome

Timeframe: Baseline through Week 52 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS): all subjects who were randomized, had a baseline post-albuterol pulmonary function test (PFT) measurement, and had at least two post-baseline, post-albuterol PFT measurements. LOCF: last observation carried forward.

Change from Baseline at each visit in post-bronchodilator forced expiratory volume in one second (FEV1). FEV1 was measured in liters (L) 30 minutes following the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus baseline value.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Baseline (n=141, 139)	2.559 liters Standard Deviation 0.771	2.524 liters Standard Deviation 0.742
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 1 (n=123, 125)	-0.066 liters Standard Deviation 0.150	-0.027 liters Standard Deviation 0.126
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 2 (n=126, 115)	-0.056 liters Standard Deviation 0.150	-0.031 liters Standard Deviation 0.128
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 3 (n=131, 119)	-0.077 liters Standard Deviation 0.185	-0.030 liters Standard Deviation 0.130
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 4 (n=121, 129)	-0.074 liters Standard Deviation 0.161	-0.022 liters Standard Deviation 0.155
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 6 (n=130, 135)	-0.070 liters Standard Deviation 0.248	-0.025 liters Standard Deviation 0.146
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 12 (n=125, 129)	-0.053 liters Standard Deviation 0.212	-0.031 liters Standard Deviation 0.182
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 18 (n=124, 125)	-0.066 liters Standard Deviation 0.226	-0.040 liters Standard Deviation 0.165
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 26 (n=120, 128)	-0.056 liters Standard Deviation 0.175	-0.038 liters Standard Deviation 0.184
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 39 (n=107, 124)	-0.088 liters Standard Deviation 0.191	-0.039 liters Standard Deviation 0.194
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 52 (n=106, 112)	-0.131 liters Standard Deviation 0.259	-0.059 liters Standard Deviation 0.234
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 52 LOCF (n=141, 139)	-0.113 liters Standard Deviation 0.261	-0.062 liters Standard Deviation 0.225

PRIMARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg) 30 minutes following the administration of albuterol. Change from Baseline: mean DLco (mL/min/mmHg) at observation minus baseline value.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Baseline (n=141, 139)	23.023 mL/min/mmHg Standard Deviation 5.914	22.883 mL/min/mmHg Standard Deviation 6.079
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 1 (n=122, 124)	-0.574 mL/min/mmHg Standard Deviation 1.392	-0.333 mL/min/mmHg Standard Deviation 1.405
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 2 (n=126, 112)	-0.777 mL/min/mmHg Standard Deviation 1.631	-0.481 mL/min/mmHg Standard Deviation 1.290
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 3 (n=129, 118)	-0.811 mL/min/mmHg Standard Deviation 1.244	-0.506 mL/min/mmHg Standard Deviation 1.388
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 4 (n=120, 128)	-1.075 mL/min/mmHg Standard Deviation 1.425	-0.576 mL/min/mmHg Standard Deviation 1.397
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 6 (n=129, 135)	-1.017 mL/min/mmHg Standard Deviation 1.633	-0.602 mL/min/mmHg Standard Deviation 1.488
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 12 (n=125, 125)	-0.961 mL/min/mmHg Standard Deviation 1.738	-0.477 mL/min/mmHg Standard Deviation 1.588
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 18 (n=124, 123)	-1.024 mL/min/mmHg Standard Deviation 1.774	-0.549 mL/min/mmHg Standard Deviation 1.601
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 26 (n=119, 127)	-0.849 mL/min/mmHg Standard Deviation 1.914	-0.477 mL/min/mmHg Standard Deviation 1.706
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 39 (n=107, 123)	-1.016 mL/min/mmHg Standard Deviation 1.649	-0.395 mL/min/mmHg Standard Deviation 1.767
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 52 (n=105, 110)	-1.483 mL/min/mmHg Standard Deviation 1.944	-0.798 mL/min/mmHg Standard Deviation 1.967
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 52 LOCF (n=141, 139)	-1.426 mL/min/mmHg Standard Deviation 1.856	-0.682 mL/min/mmHg Standard Deviation 1.958

SECONDARY outcome

Timeframe: Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) at each visit. FEV1 was measured in liters (L) before the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus mean baseline value.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Baseline (141, 139)	2.435 liters Standard Error 0.748	2.412 liters Standard Error 0.727
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 1 (123, 125)	-0.057 liters Standard Error 0.142	-0.035 liters Standard Error 0.131
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 2 (n=127, 117)	-0.065 liters Standard Error 0.159	-0.034 liters Standard Error 0.150
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 3 (n=130, 121)	-0.067 liters Standard Error 0.185	-0.044 liters Standard Error 0.171
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 4 (n=123, 130)	-0.076 liters Standard Error 0.185	-0.037 liters Standard Error 0.181
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 6 (n=130, 135)	-0.059 liters Standard Error 0.211	-0.034 liters Standard Error 0.170
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 12 (n=125, 130)	-0.067 liters Standard Error 0.237	-0.032 liters Standard Error 0.193
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 18 (n=125, 125)	-0.063 liters Standard Error 0.218	-0.042 liters Standard Error 0.183
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 26 (n=120, 129)	-0.058 liters Standard Error 0.190	-0.043 liters Standard Error 0.195
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 39 (n=108, 124)	-0.076 liters Standard Error 0.195	-0.044 liters Standard Error 0.186
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 52 (n=106, 112)	-0.136 liters Standard Error 0.259	-0.056 liters Standard Error 0.230
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Week 52 LOCF (n=141, 139)	-0.119 liters Standard Error 0.259	-0.058 liters Standard Error 0.222

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Baseline (n=141, 139)	23.034 ml/min/mmHg Standard Deviation 5.921	22.911 ml/min/mmHg Standard Deviation 6.059
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 1 (n=123, 125)	-0.749 ml/min/mmHg Standard Deviation 1.467	-0.452 ml/min/mmHg Standard Deviation 1.220
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 2 (n=126, 114)	-0.835 ml/min/mmHg Standard Deviation 1.353	-0.456 ml/min/mmHg Standard Deviation 1.485
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 3 (n=128, 119)	-0.855 ml/min/mmHg Standard Deviation 1.407	-0.556 ml/min/mmHg Standard Deviation 1.452
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 4 (n=122, 127)	-1.120 ml/min/mmHg Standard Deviation 1.609	-0.648 ml/min/mmHg Standard Deviation 1.500
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 6 (n=129, 135)	-1.169 ml/min/mmHg Standard Deviation 1.583	-0.669 ml/min/mmHg Standard Deviation 1.441
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 12 (n=124, 128)	-1.018 ml/min/mmHg Standard Deviation 1.842	-0.725 ml/min/mmHg Standard Deviation 1.788
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 18 (n=123, 125)	-0.906 ml/min/mmHg Standard Deviation 1.756	-0.646 ml/min/mmHg Standard Deviation 1.748
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 26 (n=117, 127)	-0.945 ml/min/mmHg Standard Deviation 1.683	-0.561 ml/min/mmHg Standard Deviation 1.982
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 39 (n=106, 125)	-0.821 ml/min/mmHg Standard Deviation 1.742	-0.550 ml/min/mmHg Standard Deviation 1.805
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 52 (n=105, 111)	-1.699 ml/min/mmHg Standard Deviation 2.157	-0.911 ml/min/mmHg Standard Deviation 2.239
Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) Week 52 LOCF (n=141, 139)	-1.557 ml/min/mmHg Standard Deviation 2.109	-0.785 ml/min/mmHg Standard Deviation 2.141

SECONDARY outcome

Timeframe: Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Change from Baseline in Pre-Insulin Forced Expiratory Volume in one second (FEV1) measured in liters (L): change = FEV1 at observation minus FEV1 at Baseline.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=130 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=133 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1) Baseline (n=130, 133)	2.449 liters Standard Deviation 0.775	2.403 liters Standard Deviation 0.727
Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1) Week 9 (n=111, 108)	-0.038 liters Standard Deviation 0.235	-0.028 liters Standard Deviation 0.163
Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1) Week 51 (n=103, 119)	-0.078 liters Standard Deviation 0.227	-0.017 liters Standard Deviation 0.245
Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1) Week 51 LOCF (n=130, 133)	-0.068 liters Standard Deviation 0.237	-0.018 liters Standard Deviation 0.237

SECONDARY outcome

Timeframe: Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=128 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=131 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) Baseline (n=128, 131)	22.836 ml/min/mmHg Standard Deviation 6.087	22.718 ml/min/mmHg Standard Deviation 6.128
Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) Week 9 (n=109, 106)	-1.130 ml/min/mmHg Standard Deviation 1.663	-0.663 ml/min/mmHg Standard Deviation 1.549
Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) Week 51 (n=102, 116)	-1.156 ml/min/mmHg Standard Deviation 1.825	-0.630 ml/min/mmHg Standard Deviation 2.023
Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) Week 51 LOCF (n=128, 131)	-1.185 ml/min/mmHg Standard Deviation 1.804	-0.533 ml/min/mmHg Standard Deviation 1.990

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Change from baseline in Post-bronchodilator Forced Vital Capacity (FVC) measured in liters (L) 30 minutes following the administration of albuterol: change = FVC at observation minus FVC at Baseline.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Baseline (n=141, 139)	3.355 liters Standard Deviation 0.963	3.341 liters Standard Deviation 0.918
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 1 (n=123, 125)	-0.068 liters Standard Deviation 0.181	-0.046 liters Standard Deviation 0.134
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 2 (n=126, 115)	-0.057 liters Standard Deviation 0.190	-0.053 liters Standard Deviation 0.169
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 3 (n=131, 119)	-0.078 liters Standard Deviation 0.205	-0.068 liters Standard Deviation 0.174
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 4 (n=121, 129)	-0.065 liters Standard Deviation 0.193	-0.051 liters Standard Deviation 0.176
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 6 (n=130, 135)	-0.092 liters Standard Deviation 0.287	-0.043 liters Standard Deviation 0.173
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 12 (n=125, 129)	-0.045 liters Standard Deviation 0.222	-0.056 liters Standard Deviation 0.190
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 18 (n=124, 125)	-0.053 liters Standard Deviation 0.225	-0.069 liters Standard Deviation 0.179
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 26 (n=120, 128)	-0.061 liters Standard Deviation 0.215	-0.052 liters Standard Deviation 0.186
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 39 (n=107, 124)	-0.080 liters Standard Deviation 0.209	-0.057 liters Standard Deviation 0.213
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 52 (n=106, 112)	-0.105 liters Standard Deviation 0.288	-0.088 liters Standard Deviation 0.259
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Week 52 LOCF (n=141, 139)	-0.097 liters Standard Deviation 0.278	-0.083 liters Standard Deviation 0.247

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52

Population: Full analysis set (FAS)

Responsiveness was the percent change from the forced expiratory volume in 1 second (FEV1) value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as \[(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1\] multiplied by 100.

Outcome measures

Outcome measures
Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Baseline (n=141, 139)	5.487 percent change in FEV1 Standard Deviation 5.163	5.102 percent change in FEV1 Standard Deviation 6.416
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 1 (n=123, 125)	-0.015 percent change in FEV1 Standard Deviation 5.452	0.347 percent change in FEV1 Standard Deviation 5.429
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 2 (n=126, 115)	0.683 percent change in FEV1 Standard Deviation 5.984	0.347 percent change in FEV1 Standard Deviation 6.354
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 3 (n=130, 119)	-0.055 percent change in FEV1 Standard Deviation 6.082	0.823 percent change in FEV1 Standard Deviation 5.449
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 4 (n=121, 129)	0.056 percent change in FEV1 Standard Deviation 6.361	0.559 percent change in FEV1 Standard Deviation 5.733
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 6 (n=130, 135)	-0.460 percent change in FEV1 Standard Deviation 5.480	0.504 percent change in FEV1 Standard Deviation 6.350
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 12 (n=124, 129)	0.721 percent change in FEV1 Standard Deviation 5.972	-0.100 percent change in FEV1 Standard Deviation 6.783
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 18 (n=124, 125)	-0.095 percent change in FEV1 Standard Deviation 5.909	0.154 percent change in FEV1 Standard Deviation 7.649
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 26 (n=120, 128)	-0.186 percent change in FEV1 Standard Deviation 5.624	0.211 percent change in FEV1 Standard Deviation 5.080
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 39 (n=107, 124)	-0.283 percent change in FEV1 Standard Deviation 5.368	0.133 percent change in FEV1 Standard Deviation 5.089
Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol Week 52 (n=106, 112)	0.640 percent change in FEV1 Standard Deviation 5.338	-0.035 percent change in FEV1 Standard Deviation 6.156

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Population: Full analysis set (FAS); LOCF: last observation carried forward.

Percent predicted change from Baseline in post-bronchodilator forced expiratory volume in one second (FEV1) measured in liters (L): National Health and Nutrition Examination Survey (NHANES III) reference standard. Percent change from Baseline in post-bronchdilator FEV1 measured in liters (L): (observed value minus Baseline value) divided by Baseline value \*100%.

Outcome measures
Measure	Inhaled Insulin n=135 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=135 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Severe Hypoglycemic Event Rates 0 to 1 month (n=135, 135)	2.91 Number of events/100 subject-months.	1.48 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 1 to 2 months (n=135, 135)	5.22 Number of events/100 subject-months.	1.49 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 2 to 3 months (n=131, 134)	4.64 Number of events/100 subject-months.	2.99 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 3 to 4 months (n=128, 134)	0.78 Number of events/100 subject-months.	2.24 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 4 to 5 months (n=126, 134)	4.05 Number of events/100 subject-months.	1.51 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 5 to 6 months (n=121, 131)	3.33 Number of events/100 subject-months.	2.29 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 6 to 7 months (n=119, 131)	0.00 Number of events/100 subject-months.	0.77 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 7 to 8 months (n=115, 129)	0.89 Number of events/100 subject-months.	2.33 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 8 to 9 months (n=111, 129)	5.42 Number of events/100 subject-months.	1.55 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 9 to 10 months (n=110, 129)	0.91 Number of events/100 subject-months.	3.18 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 10 to 11 months (n=109, 125)	1.88 Number of events/100 subject-months.	2.41 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates > 11 to 12 months (n=104, 123)	3.95 Number of events/100 subject-months.	3.10 Number of events/100 subject-months.
Severe Hypoglycemic Event Rates Overall (n=135, 135)	2.89 Number of events/100 subject-months.	2.13 Number of events/100 subject-months.

Adverse Events

Inhaled Insulin

Serious events: 21 serious events

Other events: 140 other events

Deaths: 0 deaths

Subcutaneous Insulin

Serious events: 13 serious events

Other events: 136 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Inhaled Insulin n=141 Participants Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=139 Participants Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Baseline (n=141, 139)	83.698 percentage of FEV1 Standard Deviation 14.096	82.833 percentage of FEV1 Standard Deviation 15.219
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 1: % of Predicted Value (n=123, 125)	81.987 percentage of FEV1 Standard Deviation 14.441	82.878 percentage of FEV1 Standard Deviation 15.438
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 2: % of Predicted Value (n=126, 115)	81.655 percentage of FEV1 Standard Deviation 13.985	81.881 percentage of FEV1 Standard Deviation 15.017
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 3: % of Predicted Value (n=131, 119)	80.711 percentage of FEV1 Standard Deviation 13.854	82.036 percentage of FEV1 Standard Deviation 15.354
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 4: % of Predicted Value (n=121, 129)	81.093 percentage of FEV1 Standard Deviation 15.145	82.029 percentage of FEV1 Standard Deviation 14.914
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 6: % of Predicted Value (n=130, 135)	81.611 percentage of FEV1 Standard Deviation 14.553	82.016 percentage of FEV1 Standard Deviation 15.509
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 12: % of Predicted Value (n=125, 129)	82.145 percentage of FEV1 Standard Deviation 13.885	81.640 percentage of FEV1 Standard Deviation 14.673
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 18: % of Predicted Value (n=124, 125)	82.187 percentage of FEV1 Standard Deviation 14.405	81.723 percentage of FEV1 Standard Deviation 14.505
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 26: % of Predicted Value (n=120, 128)	82.941 percentage of FEV1 Standard Deviation 14.291	82.227 percentage of FEV1 Standard Deviation 14.305
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 39: % of Predicted Value (n=107, 124)	82.851 percentage of FEV1 Standard Deviation 14.447	81.847 percentage of FEV1 Standard Deviation 14.794
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 52: % of Predicted Value (n=106, 112)	80.869 percentage of FEV1 Standard Deviation 14.934	81.138 percentage of FEV1 Standard Deviation 14.461
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 52 LOCF: % of Predicted Value (n=141, 139)	80.136 percentage of FEV1 Standard Deviation 14.528	80.687 percentage of FEV1 Standard Deviation 14.671
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 1: % Change from Baseline (n=123, 125)	-2.682 percentage of FEV1 Standard Deviation 5.780	-1.238 percentage of FEV1 Standard Deviation 5.307
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 2: % Change from Baseline (n=126, 115)	-2.355 percentage of FEV1 Standard Deviation 5.909	-1.142 percentage of FEV1 Standard Deviation 5.273
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 3: % Change from Baseline (n=131, 119)	-2.943 percentage of FEV1 Standard Deviation 7.583	-1.057 percentage of FEV1 Standard Deviation 5.292
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 4: % Change from Baseline (n=121, 129)	-3.063 percentage of FEV1 Standard Deviation 6.926	-0.833 percentage of FEV1 Standard Deviation 6.172
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 6: % Change from Baseline (n=130, 135)	-2.559 percentage of FEV1 Standard Deviation 8.725	-0.957 percentage of FEV1 Standard Deviation 6.180
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 12: % Change from Baseline (n=125, 129)	-1.975 percentage of FEV1 Standard Deviation 8.495	-1.226 percentage of FEV1 Standard Deviation 7.603
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 18: % Change from Baseline (n=124, 125)	-2.437 percentage of FEV1 Standard Deviation 8.713	-1.247 percentage of FEV1 Standard Deviation 6.688
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 26: % Change from Baseline (n=120, 128)	-2.006 percentage of FEV1 Standard Deviation 6.891	-1.189 percentage of FEV1 Standard Deviation 8.013
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 39: % Change from Baseline (n=107, 124)	-3.144 percentage of FEV1 Standard Deviation 7.507	-1.466 percentage of FEV1 Standard Deviation 8.332
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 52: % Change from Baseline (n=106, 112)	-4.777 percentage of FEV1 Standard Deviation 8.794	-2.002 percentage of FEV1 Standard Deviation 10.040
Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) Week 52 LOCF: % Change from Baseline (n=141, 139)	-4.129 percentage of FEV1 Standard Deviation 9.673	-2.108 percentage of FEV1 Standard Deviation 9.652

Measure	Inhaled Insulin n=146 participants at risk Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=141 participants at risk Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Acute coronary syndrome	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	1.4% 2/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Angina pectoris	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Angina unstable	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Arteriosclerosis coronary artery	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Atrial fibrillation	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Atrial flutter	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Atrioventricular block	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Cardiac disorders Myocardial infarction	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Hiatus hernia	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Small intestinal obstruction	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
General disorders Chest pain	1.4% 2/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Hepatobiliary disorders Hepatitis alcoholic	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Abdominal wall abscess	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Erysipelas	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Gastroenteritis	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Pneumonia	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Viral infection	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Metabolism and nutrition disorders Hypoglycaemia	2.1% 3/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Metabolism and nutrition disorders Ketoacidosis	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Nervous system disorders Cerebrovascular accident	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Psychiatric disorders Alcohol abuse	0.68% 1/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.00% 0/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Asthma	2.1% 3/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	1.4% 2/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	0.71% 1/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.

Measure	Inhaled Insulin n=146 participants at risk Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous Insulin n=141 participants at risk Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Eye disorders Conjunctivitis	2.1% 3/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	6.4% 9/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Constipation	2.7% 4/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.7% 8/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Diarrhoea	6.8% 10/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	4.3% 6/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Nausea	8.2% 12/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.7% 8/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Gastrointestinal disorders Vomiting	5.5% 8/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	3.5% 5/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
General disorders Chest pain	5.5% 8/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
General disorders Fatigue	6.2% 9/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
General disorders Oedema peripheral	7.5% 11/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	9.9% 14/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Immune system disorders Seasonal allergy	2.1% 3/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Bronchitis	16.4% 24/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	12.8% 18/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Gastroenteritis	5.5% 8/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Gastroenteritis viral	3.4% 5/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Influenza	13.7% 20/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	17.7% 25/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Nasopharyngitis	19.9% 29/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	18.4% 26/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Sinusitis	9.6% 14/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	14.9% 21/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Upper respiratory tract infection	30.1% 44/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	27.7% 39/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Infections and infestations Urinary tract infection	12.3% 18/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	14.2% 20/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Metabolism and nutrition disorders Hypoglycaemia	74.7% 109/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	85.1% 120/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 10/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	9.2% 13/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Back pain	6.8% 10/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	8.5% 12/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 7/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	10.6% 15/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Musculoskeletal and connective tissue disorders Tendonitis	2.7% 4/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.7% 8/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Nervous system disorders Dizziness	7.5% 11/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	7.1% 10/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Nervous system disorders Headache	9.6% 14/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	9.9% 14/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Nervous system disorders Neuropathy peripheral	1.4% 2/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	5.0% 7/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Nervous system disorders Tremor	5.5% 8/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	12.1% 17/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Psychiatric disorders Depression	7.5% 11/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	4.3% 6/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Asthma	36.3% 53/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	44.7% 63/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Cough	19.9% 29/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	7.8% 11/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 9/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	1.4% 2/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.6% 14/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	1.4% 2/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.1% 6/146 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.	9.2% 13/141 Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.