Following changes were made: • Schedules for visits throughout the study were clarified. • Assessments at early termination were same as those being done at visit 10. • Specifics of spirometry to be done in each treatment group were clarified.

• Interdeterminate lung disease group was replaced to COPD and asthma as per the recommendations of Food and Drug Administration (FDA). • Sample size was increased to accommodate 2 treatment groups within each disease state due to projected drop-out of 35%. • Spirometry at the site would be done only to evaluate acute effects of TI inhalation powder, pre and post TI inhalation powder administration. • 30 minutes post TI inhalation powder administration time point and visit 3 assessment were added in FEV1 assessment. • HbA1c changed from visit 2 to visit 1. • Pulmonary AEs (other than cough and pulmonary exacerbations) were presented with all other AEs. • Eligibility criteria was modified as per the recommendations of FDA. • Changes in “Analysis of primary endpoint” was done to perform analysis separately within each disease state of COPD and asthma. • Analysis and endpoints were clarified. • Diabetic education would be performed by the site as part of routine care. • Addition of X-ray exclusion in exclusion criteria. • Clarification of exacerbation and use of corticosteroids and antibiotics for a respiratory Infection. • Elimination of urine cotinine test at Visits 2, 5, 6, 7, 8, 9, and 11. • Clarification of pulmonary function tests (PFT) testing and reporting procedures. • Hypoglycemia as Serious adverse event was clarified. • Imputation methods were clarified as LOCF.

• 3-month follow-up period was changed to 2-month follow-up period. • 2-week period between the screening visit and the baseline visit was changed to 3-week to establish personal best peak expiratory flow over a 2-week period prior to initiation of the trial drugs. • Technosphere® Inhalation Powder was deleted as an IMP from the protocol. • Introduction section was updated to incorporate updated TI inhalation powder information. • Text of secondary objectives was modified to be more specific. • Trial diagram was modified to reflect new trial design. • Study population selection and other related information were modified to reflect new trial design. • Inclusion criteria and exclusion criteria were modified to reflect the correct inclusion criteria. • Trial stopping rules were added as per the recommendations of FDA. • Subjects received an electronic peak expiratory flow (PEF) meter and trained on proper usage at the clinic site. It was used to accurately measure daily morning and evening peak expiratory flow rates (PEFR). • PreprandiaL capillary plasma glucose was changed to 70-130 mg/dL (3.9-7.2 mmol/L) as per the 2009 American Diabetes Association (ADA) recommendations. • Dosing guidelines were updated as per the updated TI inhalation powder information.

• Introduction section was updated as per the updated TI inhalation powder information. • Device description, study drug packaging, packaging and labeling etc. was revised to reflect the to-be-marketed inhaler. • TI inhalation powder cartridges in film/foil should be stored in refrigerated (at 2°C to 8°C or 36°F to 46°F for long term storage. • Definition of Serious adverse event, hypoglycemia and cough were updated. • Trial activities were revised for clarity. • Data collection, database quality assurance, recording of data etc. were revised to reflect that remote data capture would be used for the trail. • Schedule of PFTs were revised to reflect the actual sequence of testing done at the PFT laboratory.

• 2-week screening period was amended to allow sufficient time to complete all screening procedures. • “PEF” was changed to “PEFR” for better clarity. • Time and events schedule were revised for better clarity. • Range of Body mass index (BMI) and HbA1c and other parameters in inclusion criteria and exclusion criteria were revised to study a broader study population and for clarification. • All primary and secondary analysis were planned to be conducted using mixed model repeated measure (MMRM) approach. • List of inhaled short-acting beta-agonists was updated based on more recently approved medications available for the treatment of asthma and COPD. • Definitions of pulmonary exacerbation, AEs, hypoglycemia, cough etc. were revised based on current CDISC definitions and clarifications. • Removal of subjects from the trial or study drug, rules for stopping the trial were revised to streamline reporting process. • Efficacy analysis would be done using MMRM analysis on full analysis set (FAS) population. • Dosing guidelines for study drug was revised for clarification on TI dose initiation and instructions for dose adjustments. • Schedule of lung diffusion testing was corrected.

• Time and events schedule were revised to provide greater clarity. • Range of BMI and HbA1c and other parameters of inclusion criteria and some parameters in exclusion criteria were revised to study a broader study population and for clarification. • List of inhaled short-acting beta-agonists was updated based on more recently approved medications available for the treatment of asthma and COPD. • Definitions of pulmonary exacerbation, AEs, hypoglycemia, cough etc. were revised based on current CDISC definitions and clarifications. • Removal of subjects from the trial or study drug, rules for stopping the trial were revised to streamline reporting process. • Definition of intent-to-treat (ITT) population was replaced with FAS population that allowed the MMRM analysis to utilize all randomized subjects even when baseline or post baseline data was missing. • Efficacy analysis would be done using MMRM analysis on FAS population.