Conditions: Diabetes Mellitus, Type 1
Keywords: diabetes time in range inhaled insulin continuous glucose monitoring type 1 diabetes hypoglycemia post prandial hypergylcemia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 60
Healthy volunteers: yes

Brief summary:
This is an investigator-initiated, prospective, randomized, multicenter, parallel, open-label, pilot clinical trial evaluating the efficacy of TI for PPBG, PPGE, and time-in-range on CGM download in patients with T1D. TI is an inhaled ultra-rapid-acting insulin, approved by the FDA for use in patients with diabetes. This is a pilot, real-life study where patients will continue their routine diabetes care and use post-meal correction dosages as deemed necessary for normalizing PPBG as per the protocol.

This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

All patients will use real-time CGM (Dexcom G5®, San Diego, CA), which will be provided at the randomization visit for their day-to-day diabetes care. CGM data will be downloaded at every clinic visit on a secured computer. The data will be analyzed after the study for different primary and secondary end points. All patients will be allowed to keep the CGM after the study is over for their day-to-day diabetes care.

Detailed description:

Arms:
arm 1: Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG ( post prandial blood glucose) arm 2: Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals.

Interventions: intervention 1: Technosphere insulin
Intervention descriptions: intervention 1: This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

Protocol document:
Prot_SAP_001.pdf: 
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Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin in Patients 
with Type 1 Diabetes on Multiple Daily Injections: Investigator-Initiated A Real-life 
Pilot Study—STAT Study 
 
PI:  Satish K. Garg MD 
University of Colorado, Barbara Davis Center for Diabetes 
 
Study Sites and Local PIs: 
1. PI:  Halis Kaan Akturk, MD 
University of Colorado Denver, Barbara Davis Center for Diabetes, 
1775 Aurora Court Aurora, CO 80045 
2.  PI:  Bruce Bode, MD 
Atlanta Diabetes Associates 1800, Howell Mill Rd #450, Atlanta, GA 30318 
3. PI:  Anne Peters, MD 
USC Westside Center for Diabetes, 9033 Wilshire Blvd #406, Beverly Hills, 
CA 90211 
4.  PI:  Leslie Klaff, MD and Ronald Brazg, MD 
Rainier Clinical Research Center, 723 SW 10th St #100, Renton, WA 98057 
5.  PI:  Timothy S. Bailey, MD 
AMCR Institute, 700 West El North Parkway, Suite 201, Escondido, CA  92026 
 
 


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Abbreviations: 
A1c 
 
 
Hemoglobin A1c 
AE 
 
 
Adverse Event 
AUC  
 
Area Under The Curve 
CGM  
 
Continuous Glucose Monitoring 
CBC  
 
Complete Blood Count 
CMP  
 
Complete metabolic panel 
CRO  
 
Contract Research Organization 
DKA  
 
Diabetic Ketoacidosis 
FEV1  
 
Forced Expiratory Volume In 1 Second 
FDA  
 
Food and Drug Administration 
IRB 
 
 
Intuitional Review Board 
MDI 
 
 
Multiple Daily Injections 
NL 
 
 
Novolog®, Insulin Aspart 
SAE  
 
Serious Adverse Event 
SMBG 
 
Self-Monitoring of Blood Glucose 
PPBG  
 
Post-prandial Blood glucose 
PPGE  
 
Post-prandial Glucose Excursion 
T1D 
 
 
Type 1 Diabetes 
TI 
 
 
Afrezza®, Technosphere Insulin 
 
 


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Clinical Trial Summary 
Title 
Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin in 
Patients with Type 1 Diabetes on Multiple Daily Injections: 
Investigator-Initiated, A Real-life Pilot Study—STAT Study 
Trial Location 
Multi-center (USA) 
Study Objectives 
Primary objectives: 
1. Improved time in range (70-180 mg/dl) with technosphere 
insulin (TI) on continuous glucose monitoring (CGM) 
2. Better post-prandial glucose excursions (PPGE) (1-4 hours 
after meals) with TI 
Secondary objectives: 
1. To assess glucose variability (standard deviation and/or 
coefficient variation), 
2. The area under the curve (AUC) in the post-prandial blood 
glucose (PPBG) and PPGE, 
3. Change in A1c in one-month treatment, 
4. To determine above the target (>180 mg/dl) on CGM, and 
5. To evaluate hypoglycemia (below the target <70, <60, <50 
mg/dl) on CGM 
Study Design 
Randomized, open-label, parallel, multi-center, prospective, 
investigator-initiated 
Study Population 
Main Selection 
Criteria 
Inclusion criteria: 
1. Signed informed consent before any study-related activities, 
2. Male or female aged 18-70 years, 
3. Type 1 diabetes mellitus (T1D) duration more than six months, 


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4. Treatment with multiple daily injections (MDI) for at least three 
months before screening visit; stable insulin dose for the last 
one month, 
5. No use of any oral anti-diabetics, any other form of insulin other 
than mentioned in the protocol, or any other type of injections 
such as glucagon-like-peptide-1 (GLP-1) analogs, pramlintide 
or insulin/GLP-1 analog combinations, 
6. A1c between 6.5 to 10%, 
7. Willingness to routinely collect at least two blood glucose 
measurements per day to calibrate the CGM. Beyond the 
calibrations, patients may use CGM for necessary action 
without having to confirm with fingersticks self-monitoring blood 
glucose (SMBG), as approved by the Food and Drug 
Administration (FDA), 
8. BMI ≤35 kg/m2, 
9. Ability and willingness to adhere to the protocol including 
clinical and phone visits and 4-week-long CGM wear, 
10. Using insulin glargine or insulin degludec as basal insulin, 
11. Able to use and understand CGM data, 
12. Willing to complete phone and clinic visits, 
13. Patients who eat three main meals in a day (breakfast, lunch, 
and dinner), 
14. Ability to speak, read, and write English, and 
15. Patients prandial insulin need must be <18 units per meal 
 
Exclusion criteria: 
1. Use of any other diabetic medication other than allowed in the 
protocol, 
2. Pregnant or intention to become pregnant during the study, or 
not using adequate birth control methods, 


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3. Severe unexplained hypoglycemia requiring emergency 
treatment in the previous three months, 
4. Use of systemic or inhaled corticosteroids, 
5. History of hemoglobinopathies, 
6. Diagnosis of anemia, 
7. Post-renal transplantation, currently undergoing dialysis, 
creatinine >2.0 mg/dl or a calculated creatinine clearance of 
<50 mL/min, 
8. Advanced or unstable retinopathy needing laser procedure or 
vitrectomy, 
9. History of pancreatitis, 
10. Extensive skin changes/diseases that inhibit wearing a sensor 
on normal skin, 
11. Known allergy to adhesives, 
12. Known allergy to study medication, 
13. Participation in another investigational study protocol within 30 
days before enrollment, 
14. Known chronic obstructive pulmonary disease, pulmonary 
hypertension, asthma, pulmonary fibrosis, or any chronic 
pulmonary infection, or any systemic disease that primarily 
affects the lungs. History of any pulmonary nodule will be 
excluded to participate in the study, 
15. Active smokers, 
16. Marijuana users, 
17. Insulin pump users, 
18. Expected acetaminophen use during CGM, 
19. Using insulin detemir or NPH as basal insulin, 
20. Patients who use more than 18 units per meal, 
21. Any other condition, as determined by the investigator, which 
could make the subject unsuitable for the trial, impairs the 


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subject’s suitability for the trial, or impairs the validity of the 
informed consent. 
Total patients 
Up to 75 enrolled  for a total of 60 randomized patients to account for 
dropouts/screen fails 
Study Treatment 
Investigational 
medication(s) 
 
Treatment group: Technosphere insulin (Afrezza®) 
TI will be supplied as single-use cartridges of inhaled insulin of 4 or 8 
or 12 units each. 
Control group: Insulin aspart (Novolog®) {NL} 
Novolog® will be supplied as 100 U/mL solution for SC injection in the 
Novolog® Flexpen™ disposable pen. 
Routes of 
administration 
Treatment group: TI Inhaler 
Control group: Subcutaneous injection of NL 
Dose regimen and 
adjustment 
Patients will continue their routine meal and correction coverage, if 
applicable. Tables are for recommendations only and will be used as 
guidance. Since this is a real-life pilot study, patients will not be 
mandated to use corrections in the NL group. However, in the TI 
group, patients will use the conversion table from their current prandial 
insulin dosage as provided (Table 1A). Patients in the TI group will be 
recommended to use additional post-meal TI bolus as recommended 
to optimize PPBG {2-hour correction will be used only if blood glucose 
is >201 mg/dl and has not decreased by ≥ 50 mg/dl between 1 and 2-
hours} (Table 1B). 
Conversion  
Table 1A 
Injected 
mealtime insulin 
dose 
Technosphere 
insulin dose 
Up to 4 units 
4 units 
5-8 units 
8 units 
9-12 units 
12 units 
13-16 units 
16 units 


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17-20 units 
20 units 
 
Correction 
Table 1B 
 
Blood glucose 
1-hour 
2-hour 
<150 mg/dl 
- 
- 
151-200 mg/dl 
4 units 
- 
>201 mg/dl 
8 units 
4 units 
Basal insulin 
Insulin degludec (Tresiba®), insulin glargine (Lantus®, Basaglar®, 
Toujeo®) 
Route of 
administration 
Subcutaneous injection 
Dose regimen 
Patients will continue their current dose basal insulin once or twice a 
day. 
Statistical 
considerations 
Randomization: Patients will be assigned to TI or NL 1:1 
randomization. 
Sample size determination: Power Analysis is based on the studies 
done in patients with diabetes. This sample size will provide 80% 
power to detect a difference in the primary endpoint of time in the 
range of 11%, assuming a standard deviation of 15% and 97% power 
to detect a difference of 1.0 glucose excursion post-prandially, 
assuming a standard deviation of 1.0. 
Analysis population: Statistical analysis will be done after the study is 
complete. The analysis will be conducted on an intent to treat (ITT) 
population. 
Study duration 
Screening visit followed by randomization visit (up to 7 days) 
4-week treatment period (2 phone visits, 2 clinic visits) 
1-week follow-up period (1 phone visit) 
Total of 6 weeks 
 


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Sponsor:     Investigator initiated trial supported by Mannkind, Corp, Valencia, CA. 
 
Project Overview 
This is an investigator-initiated, prospective, randomized, multicenter, parallel, 
open-label, pilot clinical trial evaluating the efficacy of TI for PPBG, PPGE, and time-in-
range on CGM download in patients with T1D. TI is an inhaled, ultra-rapid-acting insulin, 
approved by the FDA for use in patients with diabetes. This is a pilot, real-life study 
where patients will continue their routine diabetes care and use post-meal correction 
dosages as deemed necessary for normalizing PPBG as per the protocol. 
This multi-center study will enroll 75 patients with T1D for a total of 60 
randomized patients to account for dropouts/screen fails, A1c values between 6.5 to 
10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are 
randomized into the NL arm will continue using their usual prandial insulin dose before 
meals. Patients who are randomized into the TI arm will be instructed to dose before the 
meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG 
(Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 
clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and 
NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, 
complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the 
screening visit. 
All patients will use real-time CGM (Dexcom G5®, San Diego, CA), which will be 
provided at the randomization visit for their day-to-day diabetes care. CGM data will be 
downloaded at every clinic visit on a secured computer. The data will be analyzed after 


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the study for different primary and secondary end points. All patients will be allowed to 
keep the CGM after the study is over for their day-to-day diabetes care. 
 
Primary objective: 
1. Improved time in range (70-180 mg/dl) with TI on CGM 
2. Better PPGE (1-4 hours after meals) with TI 
 
Secondary objectives: 
1. To assess glucose variability (GV) (standard deviation and/or coefficient 
variation), 
2. The area under the curve (AUC) in the PPBG and PPGE, 
3. Change in HbA1c in one-month treatment, 
4. To determine above the target (>180 mg/dl) on CGM, and 
5. To evaluate hypoglycemia (below the target <70, <60, <50 mg/dl) on CGM. 
 
Research Design 
What do we intend to do? 
We plan to execute an investigator-initiated, treat-to-target (TTT), multi-center, 
prospective randomized, parallel, open-label pilot clinical trial evaluating the efficacy of 
TI for lowering PPBG and PPGE in 60 adult patients (18 to 70 years) with T1D when 
compared with NL over a 4-week treatment period. The study protocol is registered with 
the NCT Government website: ClinicalTrials.Gov. NCT03143816 
 
How are we going to do the work? 
The Barbara Davis Center for Diabetes (BDC), primarily a leading T1D clinical 
and research center equipped for large-scale clinical research, will enroll approximately 
15-20 patients (Halis Kaan Akturk, MD). The other four sites are: Atlanta Diabetes 
Associates (Bruce Bode, MD), USC Westside Center for Diabetes (Anne Peters, MD), 
AMCR Institute (Timothy Bailey, MD), and Rainier Clinical Research Center (Leslie 
Klaff, MD, and Ronald Brazg, MD). All other sites will enroll approximately 10-15 


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patients. Necessary personnel from all sites will attend an investigator’s meeting likely in 
Denver in June 2017, which will be organized and conducted before the trial initiation. 
All patients will sign an informed consent form approved by the respective institutional 
review boards (IRB). The study will be coordinated by an external contract research 
organization (CRO), and all sites will be monitored at least once during the study. 
 
How will the sites communicate? 
Throughout the duration of the study, specific events will also be communicated 
by CRO between secondary sites and the primary investigator site. These events 
include protocol exemption, and waiver requests including failed inclusion or exclusion 
criteria. The patients will be screened within 2 weeks for A1c deviation. All serious 
adverse events (SAEs) will be reported to the CRO and the principal investigator within 
24 hours. 
 
What is the study population? 
The study population will consist of patients with T1D currently receiving care at 
all respective study sites as listed on the front page. All investigators will attempt to 
recruit males and females with T1D from a variety of ethnic groups for participation in 
this study. Participants selected for this trial will be adult males and females (18-70 
years old) with BMI ≤35.0, diabetes duration >6 months, A1c between 6.5–10% with 
T1D, who have not taken any oral anti-diabetics or any other insulin other than 
mentioned in the protocol or GLP-1 analog injections or any combination of insulin/GLP-
1 analog injections in the last three months (detailed in Appendix 2 and 3). One repeat 
A1c will be allowed within two weeks of the screening phase. Patients who need more 
than 18 units of prandial insulin before meals will be excluded from the study. Only 
patients taking glulisine (Apidra®), lispro (Humalog®), or aspart (Novolog®) as their 
prandial insulin at baseline will be allowed in the study. 
 
How are patients being selected for the study? 
Patients will be randomly selected from the patient population at all sites. First 
recognized by the investigator, coordinator, or from a computer-generated list based on 


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entry criteria, patients who qualify will be offered to participate in the study on a first 
come basis. Patients who appear to fit the inclusion/exclusion criteria as mentioned in 
Appendix 2 and 3 during prescreening will be screened. 
 
What are the treatment groups? 
There are two parallel treatment groups. Beginning the day after visit 2, week 1, 
patients in the TI treatment group will use only TI for meals and corrections. Patients in 
the comparison group will be using NL for meals as they use it in real life. All patients 
will be provided with TI and insulin aspart for the duration of the study. All basal insulin 
(Toujeo®, Lantus®, Basaglar®, Tresiba®) except NPH and detemir (Levemir®) are 
allowed before and during the study as a part of MDI regimens. Basal insulin will not be 
provided throughout the study period. 
 
What is your assignment strategy? 
The patients will be assigned in a 1:1 fashion to either the TI or NL group. Sites 
will be responsible for supplying TI, NL, and other necessary materials to the patients 
related to the study. The Barbara Davis Center for Diabetes will be responsible for 
randomization using a computer system (Janet Snell-Bergeon, PhD). All patients will be 
provided with a CGM (Dexcom G5®, San Diego, CA) and six sensors for the duration of 
the study. Patients will be allowed to keep the CGM systems for their personal use after 
the study. The CGM data will be downloaded and analyzed for different GV indices at all 
clinical visits. 
 
What are sample size calculations? 
Sixty (60) patients will be randomized into the TI and NL groups, and the study 
will likely initiate in summer of 2017. Power Analysis is based on the studies done in 
patients with diabetes. This sample size will provide 80% power to detect a difference in 
the primary end point of time in the range of 11%, assuming a standard deviation of 
15%, and 97% power to detect a difference of 1.0 glucose excursion post-prandially, 
assuming a standard deviation of 1.0. 
 


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What is the schedule of events for the treatment groups? 
All patients will participate in a 1-2 hour screening visit 1, week-1. In the same 
week, patients will be randomized into one of the two treatment groups during baseline 
visit 2 (week 0). The treatment group will only use TI for rapid acting insulin for meals 
and corrections. The control group will only use NL for rapid acting insulin for meals. 
The patients in the control group will continue to use their respective treatments for four 
weeks with no predetermined change in dosage or titration. The patients in the TI group 
will use TI insulin as prandial insulin and for PPBG correction at 1- and 2-hours after 
main meals. Three main meals should be at least 4 hours apart from each other. 
Because the duration of action of TI is shorter, but ultra-rapid in onset compared to NL, 
patients in the treatment group can use TI insulin for correction dose(s) at 1-hour and 2-
hour after the meal dose, if BG is over 150 mg/dl. All patients in the treatment group will 
use a dose-conversion chart that will be provided at randomization for meals according 
to their usual prandial insulin dose (Table 1A). The study design is summarized in 
Figure-1. All patients in the treatment group will be given the option of using correction if 
PPBG at 1-hour after the meal is between 151-200 mg/dl by 4 units of TI, and if PPBG 
is over 201 mg/dl by 8 units of TI (Table 1B). If PPBG does not decrease more than 50 
mg/dl, and still over 201 mg/dl at 2-hour after the meal, they will be given the option of 
using 4 units of TI (Table 1B). All patients in the treatment group will be instructed on 
proper use of the TI inhaler. At all clinical visits, all insulin dosages will be recorded. All 
data will be downloaded and saved on a secured computer. FEV1 at baseline, after 2-
week of treatment and at the end of the study will be done for all patients. Appendix-1 
summarizes the schedule of events. 
 
Excluded medications: 
The patients who are current smokers or have any other significant pulmonary 
disease will not be allowed to participate in the study. No marijuana consumption will be 
allowed during the study (since the effects of acute marijuana inhalations on TI 
absorption are unknown). 
All oral anti-diabetics and other forms of insulin and injectable medications other 
than mentioned in the protocol should not be taken in the last three months. 


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Medications that affect blood sugar, including oral anti-diabetic medications, are not to 
be used for the duration of the study. The patients must not be taking inhaled or oral 
systemic corticosteroids. 
Other drugs that interact with TI and/or NL are to be considered on a case-by-
case basis by the investigator, including herbs with hypoglycemic properties. 
 
Visit Descriptions: 
Screening, Visit 1 (Week -1): 
A screening visit: Visit 1 (Week -1). Informed consent will be obtained before 
commencement of any trial-related activities, defined as any procedure that would not 
have been performed during standard care of the subject outside of the study. 
During this visit, patients will receive a physical exam, EKG, vitals and medical 
history, demographics, and a concomitant medications list will be recorded. A blood 
draw will be performed to assess for A1c (point of care preferred), CMP, and CBC. A 
urine pregnancy test will be administered for females of childbearing potential. If the 
patient has a qualified HbA1c done in the last two weeks, it will not be repeated at the 
screening visit unless the PI deems it necessary. All patients will receive a spirometry 
(FEV1) test for screening. 
 
Baseline/Randomization, Visit 2 (Week 0) ± 3 days: 
Patients who meet the screening criteria will be randomized into one of two 
groups and necessary study medication will be dispensed. Instructions will be given on 
how to use the study medication, TI, starting the day following this visit with meals and 
corrections with doses recommended as seen in Table 1A and 1B, and to basal insulin 
regimen throughout the trial without any dose change. However, the PI may make 


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necessary changes in patients’ insulin dosages especially keeping patient safety in 
mind. Any changes that are done by the PI out of the protocol for patient safety will be 
recorded and considered in statistical analysis. 
Patients will have their vitals, weight, any adverse events, and concomitant 
medications recorded. All patients will start real-time CGM (Dexcom G5®, San Diego, 
CA) at that visit. All patients will wear CGM throughout the study. They will be allowed to 
keep the CGM after the study. They will be trained to use CGM if they do not know how 
or if they are not already on it. Patients will be trained on study paperwork (food, 
glucose and insulin diaries). Patients will continue to check their blood glucose levels 
via SMBG as they deem necessary. However, as approved by the FDA, Dexcom G5® 
data may be used to take necessary action, but all patients must calibrate the sensor 
two times a day per the label. 
All patients in the treatment group will be given the option of using correction if 
PPBG at 1-hour after the meal is between 151-200 mg/dl by 4 units of TI and if PPBG is 
over 201 mg/dl by 8 units of TI. If PPBG does not decrease more than 50 mg/dl and still 
over 201 mg/dl at 2-hours after the meal, they will be given the option of using 4 units of 
TI. All patients in the treatment group will use the recommended conversion (Table 1A) 
when they calculate their prandial insulin dose. Since this is a real-life study, patients in 
the treatment group will be instructed to use TI for post-prandial hyperglycemia; 
however, they will not be mandated. In the control group, patients will continue their 
current NL prandial dose 15 minutes before meals according to their prandial insulin 
dose. If they use correction, they will correct; however, they will not change their routine 
pre- and post-prandial management. 


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Telephone Visits (Visits 3, 5, and 7) ± 3 days (Figure-1): 
 
A phone call will be made by the study site staff to each subject at visits 3, 5, and 
7. Although the window is ± 3 days, call time will be arranged in advance during the 
clinic visit. At this visit, staff will review any adverse events and changes in medications. 
Compliance to study protocol rules and CGM use will be reviewed. 
 
Visit 4 (Week 2) ± 3 days: 
This visit will occur at Week 2. At Visit 4, study site staff will record patients’ 
vitals, weight, review of CGM data, and any adverse events and concomitant 
medications. Glucose download, insulin use/dose, and sensor glucose data will be 
discussed with the provider or the study coordinator. 
The patients will remain in the same treatment or control group. Basal, bolus, and 
total daily dose of insulin will be recorded. The patients will receive necessary refills for 
CGM supplies and study medications. All patients will be reminded about the study 
protocol and insulin conversion and correction doses (Table 1A and 1B). Patients will 
get FEV1 spirometry test. Patients who have decline more than 20% at FEV1 test at 2-
week of treatment will be excluded. 
 
End of study, Visit 6 (Week 4) or Early Termination Visit ± 3 days: 
For patients who withdraw at any point during the trial period, this visit will also 
be offered as an early termination visit (ETV). 


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Patients who complete treatment will schedule an end of study visit. This will be 
Visit 6 at Week 4. During this visit, a physical exam will be conducted. Vitals, weight, 
review of CGM data, adverse events, and concomitant medications will be recorded. 
Additional blood will be drawn for A1c or point of care A1c will be done. Unused 
medication will be returned. Active treatment with TI will end at this visit. 
Basal, bolus, and total daily dose of insulin will be recorded. After the study, 
patients will be expected to continue their previous therapy. All patients will receive a 
spirometry (FEV1) test. 
 
Risks and Justification of Procedures 
Technosphere insulin (Afrezza®) 
 
Technosphere insulin (TI) (MannKind Corporation, Valencia, CA) is a dry powder 
formulation of regular human insulin adsorbed onto technosphere microparticles for oral 
inhalation (1). Upon inhalation, these microparticles can reach the deep lung where they 
dissolve rapidly because of the physiological pH, allowing absorption of insulin into the 
systemic circulation with a time to maximum serum insulin concentration of ∼12–15 min 
(2). TI is currently approved for the treatment of Type 1 and 2 diabetes. Hypoglycemia is 
a potential risk of taking any insulin and/or TI therapy. Typical symptoms of 
mild/moderate hypoglycemia include: cold sweats, cool pale skin, nervousness or 
tremor, anxious feeling, unusual tiredness or weakness, confusion, difficulty 
concentrating, drowsiness, excessive hunger, and/or transient vision changes (3). 
Acute bronchospasm has been observed in patients with asthma and COPD 
using TI (3). TI is contraindicated in patients with chronic lung disease. Before starting 


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TI, detailed medical history, physical exam, and a spirometry (FEV1) test are mandatory 
to identify potential lung disease in all patients (3). Patients who had >20% decrease in 
FEV1 during treatment will be discontinued from using TI. 
In patients with T1D receiving basal insulin, HbA1c reduction with TI was 
noninferior to that of aspart, with less hypoglycemia and less weight gain (3). A multi-
center randomized clinical trial in patients with Type 2 diabetes showed that patients 
had significantly lower weight gain and fewer mild-to-moderate and severe 
hypoglycemic events on TI plus insulin glargine than on biaspart insulin (4). Another 
study in patients with T1D compared insulin NPH to TI and TI was not inferior for post-
prandial blood glucose control and had better results at fasting plasma glucose (5). 
Safety Measures: 
CRO will oversee safety data throughout the study via reporting of hypoglycemic 
events, adverse events, and serious adverse events (SAEs). All AEs, reported 
spontaneously by the patients, as well as those noted by the investigator or study staff, 
regardless of seriousness, severity, expectedness, or relationship to the study drug, will 
be recorded on source documents from the time of obtaining the informed consent to 7 
days after the last dose of the study drug. 
Severe hypoglycemia, a hypoglycemic episode requiring assistance or 
hospitalization with or without an SMBG or CGM data, is to be reported as a SAE. A 
hypoglycemic event “requiring assistance” is identified when the subject is unable to 
treat the event on their own. Any untoward event resulting in hospitalization, an 
extension of hospitalization, death, or threat of death will also be considered an SAE. All 
SAEs will be reported to FDA MedWatch by the CRO. 


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Statistical Analysis Plan 
Statistical analysis will be done after the study is complete. The analysis will be 
conducted on the intent to treat (ITT) population. Sample size and power calculations 
were based on the pilot study conducted at the BDC (7). 
The primary end points are to demonstrate improved time in range (70-180mg/dl) 
with TI on CGM and better PPGE (1-4 hours after meals). The secondary end points are 
to assess hypoglycemia, measure HbA1c changes, evaluate glucose variability, and to 
assess above the target (>180mg/dl) on CGM download. 
Publication Strategy 
Study results may be presented at national and international conferences 
including: the Scientific Sessions of the American Diabetes Association, European 
Association for the Study of Diabetes, Advanced Technologies for the Treatment of 
Diabetes, etc. The PI may submit the study results for publishing to peer-reviewed 
scientific journals, particularly within the fields of diabetes and endocrinology. All study 
results and data will be shared with the sponsor. 
 
 


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August 15, 2017 
 
References 
 
1. Rathbone M, Hadgraft J, Roberts M, Lane M, Leone-Bay A, Grant M. 
Technosphere/insulin: mimicking endogenous insulin release. In Modified-
Release Drug Delivery Technology. Vol. 2, 2nd ed. Rathbone M, Hadgraft J, 
Roberts M, Lane M, Eds. New York, Informa Healthcare USA, Inc., 2008, p. 673–
679 
2. Richardson PC, Boss AH. Technosphere insulin technology. Diabetes Technol 
Ther 2007;9(Suppl. 1):S65–S72pmid:17563306 
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf, April 
2017 
4. Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB; Affinity 1 
Study Group. Inhaled Technosphere Insulin Compared With Injected Prandial 
Insulin in Type 1 Diabetes: A Randomized 24-Week Trial. Diabetes Care. 2015 
Dec;38(12):2266-73. doi: 10.2337/dc15-0075. Epub 2015 Jul 15. 
5. Rosenstock J, Lorber DL, Gnudi L, Howard CP, Bilheimer DW, Chang PC, 
Petrucci RE, Boss AH, Richardson PC. Prandial inhaled insulin plus basal insulin 
glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre 
randomised trial. Lancet. 2010 Jun 26;375(9733):2244-53. doi: 10.1016/S0140-
6736(10)60632-0. 
6. Skyler JS, Weinstock RS, Raskin P, et al; Inhaled Insulin Phase III Type 1 
Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in 
type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes 
Care 2005;28:1630–1635pmid:15983312 
7. Garg SK, Kelly W, Freson B, Ritchie P. Treat-to-target technosphere insulin 
study in adult subjects with type 1 diabetes. Poster presented at American 
Diabetes Association 2011 annual meeting. 
 
 


Version 3 
August 15, 2017 
 
Table-1A Injected insulin to technosphere insulin conversion chart at study 
initiation 
 
Injected 
mealtime 
insulin dose 
Technosphere 
insulin dose* 
Up to 4 units 
4 units 
5-8 units 
8 units 
9-12 units 
12 units 
13-16 units 
16 units 
17-20 units 
20 units 
 
*Investigators may change the dosage based on patient safety, this table will be used 
as a guide. Patients who take more than 18 units on insulin aspart per meal will be 
excluded from the study. 
 
 
 
 
Table-1B Correction doses for technosphere insulin group 
 
Blood glucose 
1-hour 
2-hour 
<150 mg/dl 
- 
- 
151-200 mg/dl 
4 units 
- 
>201 mg/dl 
8 units 
4 units* 
 
*2-hour correction will be used only if blood glucose is >201 mg/dl and has not 
decreased by ≥ 50 mg/dl between 1 and 2-hours. 
 
 


Version 3 
August 15, 2017 
 
Appendix-1 Schedule of events 
 
*HbA1c test may not be waived at Visit 1 if the patient had an A1C done in the last 2 weeks. 
+All insulin (basal and prandial) will be recorded in a diary provided. 
Visit 
1 
2 
3 
4 
 5 
6 
7 
Week 
-1 
0 
1 
2 
3 
4 
5 
Visit Type 
Clinic 
Clinic 
Phone 
Clinic 
Phone 
Clinic 
Phone 
Assessment 
Screening 
and 
Baseline 
Randomization 
Treatment 
week 
Treatment 
week 
Treatment 
week 
Treatment 
week 
Post-
study 
follow up 
 
Final 
Early 
termin
ation 
Day (±3) 
-7 
0 
7 
14 
21 
28 
35 
Informed 
consent-
Eligibility criteria 
x 
 
 
 
 
 
 
 
Demographic 
Data, Medical 
History 
x 
 
 
 
 
 
 
Concomitant 
medications 
x 
x 
x 
x 
x 
x 
 
Adverse events 
 
 
x 
x 
x 
x 
x 
Physical exam 
x 
x 
 
x 
 
x 
 
EKG 
x 
 
 
 
 
 
 
Urine 
pregnancy test 
if applicable 
x 
 
 
 
 
 
 
HbA1c* 
x 
 
 
 
 
x 
 
Complete blood 
count 
x 
 
 
 
 
 
 
Complete 
metabolic panel 
x 
 
 
 
 
 
 
Spirometry(FEV
1) 
x 
 
 
x 
 
x 
 
Vital 
signs/weight 
x 
x 
 
x 
 
x 
 
Randomization 
 
x 
 
 
 
 
 
Record 
basal,bolus, 
total insulin 
dose+ 
x 
x 
 
x 
 
x 
 
Dispense TI 
 
x 
 
x 
 
 
 
Dispense insulin 
aspart 
 
x 
 
x 
 
 
 
Dexcom CGM-
training and 
dispense CGM 
 
x 
 
 
 
 
 
CGM 
change/downloa
d/ removal 
 
 
 
x 
 
x 
 
Glucose meter 
download 
 
x 
 
x 
 
x 
 
TI-NL 
conversion 
chart dispense 
and education 
 
 
x 
 
x 
 
 
 
Compliance 
check 
 
 
x 
x 
x 
x 
 


Version 3 
August 15, 2017 
 
 
 


Version 3 
August 15, 2017 
 
Appendix-2 
Inclusion Criteria: 
Patients that meet the following criteria will be considered for admission to the study: 
1. Signed informed consent before any study-related activities, 
2. Male or female aged 18-70 years, 
3. Type 1 diabetes mellitus duration more than six months, 
4. Treatment with MDI for at least three months before screening visit; stable insulin 
dose for the last month, 
5. No use of any oral anti-diabetics, any other forms of insulin other than mentioned 
in the protocol, or any other types of injections such as GLP-1 analogs, 
pramlintide or insulin/GLP-1 analog combinations, 
6. A1c between 6.5 to 10%, 
7. Willingness to routinely practice at least two blood glucose measurements per 
day needed to calibrate the CGM. Beyond the calibrations, patients may use 
CGM for necessary action without having to confirm with fingersticks (SMBG), as 
approved by the FDA, 
8. BMI ≤ 35 kg/m2, 
9. Ability and willingness to adhere to the protocol including clinical and phone visits 
and 4-week-long CGM wear, 
10. Using insulin glargine or insulin degludec as basal insulin, 
11. Able to use and understand CGM data, 
12. Willing to complete phone and clinic visits, 
13. Patients who eat three main meals in a day (breakfast, lunch, and dinner), 
14. Ability to speak, read, and write English, 
15. Patient’s prandial insulin need must be <18 units per meal. 
 
 


Version 3 
August 15, 2017 
 
Appendix-3 
Exclusion Criteria: 
Patients will be excluded from the study if any of the following apply: 
1. Use of any other diabetic medication other than allowed in the protocol, 
2. Pregnant or intent to become pregnant during the study or not using adequate 
birth control methods, 
3. Severe unexplained hypoglycemia requiring emergency treatment in the previous 
three months, 
4. Use of systemic or inhaled corticosteroids, 
5. History of hemoglobinopathies, 
6. Diagnosis of anemia, 
7. Post-renal transplantation, currently undergoing dialysis, creatinine >2.0 mg/dl or 
a calculated creatinine clearance of <50 mL/min, 
8. Advanced or unstable retinopathy needing laser procedure or vitrectomy, 
9. History of pancreatitis, 
10. Extensive skin changes/diseases that inhibit wearing a sensor on normal skin, 
11. Known allergy to adhesives, 
12. Known allergy to study medication, 
13. Participation in another investigational study protocol within 30 days before 
enrollment, 
14. Known chronic obstructive pulmonary disease, pulmonary nodule, pulmonary 
hypertension, asthma, pulmonary fibrosis or any chronic pulmonary infection, or 
any systemic disease that primarily affects the lungs, 
15. Active smokers, 
16. Marijuana users, 
17. Insulin pump users, 
18. Expected acetaminophen use during CGM, 
19. Using insulin detemir or NPH as basal insulin, 
20. Patients who use more than 18 units per meal, 


Version 3 
August 15, 2017 
 
21. Any other condition, as determined by the investigator, which could make the 
subject unsuitable for the trial, impairs the subject’s suitability for the trial, or 
impairs the validity of the informed consent 
 


Version 3 
August 15, 2017 
 
Appendix-4 
Discontinuation Criteria: 
1. A major change in exercise regimen during study participation, 
2. Diabetic ketoacidosis, 
3. Development of pancreatitis, 
4. Pregnancy, 
5. A decline in glucose control or an increase in hypoglycemia which, in the opinion 
of the PI, is considered to compromise patient safety, 
6. Initiation of any other insulin or other injectable or oral form of anti-diabetics 
during the study other than the mentioned control or intervention group 
medications, 
7. Developing significant shortness of breath or intolerance and cough to inhaled 
insulin, and/or 
8. Decline >20% in FEV1 test as compared to baseline during TI treatment. All 
patients will receive a spirometry test (FEV1) at baseline, visit-4 and at the end of 
the study. 
9. Acetaminophen use during CGM (4-week treatment period) 
 
 


Version 3 
August 15, 2017 
 
Figure-1 Flow diagram of the study 
 
 
 

ICF_002.pdf: 
 
<<CF-Main Approval Stamp - Approved>> 
Revised 8/15/2017 
Page 1 of 15 
Subject Initials 
 
RESEARCH SUBJECT INFORMATION AND CONSENT FORM 
1 
 
2 
 
3 
TITLE: 
Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin 
4 
in Patients with Type 1 Diabetes on Multiple Daily Injections: 
5 
Investigator-Initiated A Real-life Pilot Study—STAT Study 
6 
 
7 
PROTOCOL NO.: 
STAT2017 
8 
 
WIRB® Protocol #20171148 
9 
IRB #17-0427 
10 
 
11 
SPONSOR: 
Mannkind Corporation 
12 
 
13 
CO-INVESTIGATORS: 
Satish K. Garg, MD 
14 
A-140 
15 
1775 Aurora Court 
16 
Aurora, Colorado 80045 
17 
United States 
18 
 
19 
 
Halis Kaan Akturk, MD 
20 
 
1775 Aurora Court 
21 
 
A140 
22 
 
Aurora, Colorado 80045 
23 
 
United States 
24 
 
25 
SITE(S): 
University of Colorado Denver 
26 
Barbara Davis Center for Diabetes 
27 
A-140 
28 
1775 Aurora Court 
29 
Aurora, Colorado 80045 
30 
United States 
31 
 
32 
STUDY-RELATED 
33 
PHONE NUMBER(S): 
Satish K. Garg, MD 
34 
303-724-6713 
35 
303-908-2132 (24 hours) 
36 
 
37 
 
Halis Kaan Akturk, MD 
38 
 
303-724-0467 
39 
 
402-996-0040 (24 hours) 
40 
 
41 
 
Christie Beatson, RD, CDE 
42 
 
303-724-6761 
43 
 
44 
SUB- 
45 
INVESTIGATOR(S): 
Sarit Polsky, MD 
46 
 
Hal Joseph, PA-C 
47 
 
Micaela Marker, PA-C 
48 


 
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Subject Initials 
 
 
Rachel Garcetti, PA-C 
1 
 
2 
STUDY 
3 
COORDINATOR(S): 
Christie Beatson, RD, CDE 
4 
303-724-6761 
5 
 
6 
 
7 
This consent form may contain words that you do not understand.  Please ask the study doctor or 
8 
the study staff to explain any words or information that you do not clearly understand.  You may 
9 
take home an unsigned copy of this consent form to think about or discuss with family or friends 
10 
before making your decision. 
11 
 
12 
Purpose of the Study 
13 
The purpose of this study is to find out of there is an improvement in glucose variability 
14 
measured by continuous glucose monitoring (CGM) and comparing the effects of inhaled 
15 
technosphere insulin with injectable insulin aspart on A1c and blood sugar in people with type 1 
16 
diabetes (T1D). This study will investigate if using inhaled technosphere insulin with meals and 
17 
after meals for corrections is helpful to achieve your target in diabetes care compared to using 
18 
injected insulin. 
19 
 
20 
All of the medications and devices that will be used in this study are already approved by the 
21 
U.S. Food and Drug Administration (FDA) to be used in patients with T1D. There is no 
22 
investigational device or medication in this study. 
23 
 
24 
Technosphere insulin (Afrezza®) is a rapid acting inhaled insulin indicated to improve glycemic 
25 
control in adult patients with T1D. It will be mentioned as inhaled insulin in this consent form. 
26 
 
27 
Aspart insulin (Novolog®) is a rapid acting injectable insulin indicated to improve glycemic 
28 
control in patients with T1D. It will be mentioned as injectable insulin in this consent form. 
29 
 
30 
Afrezza® and Novolog® are both approved medications by the U.S. Food and Drug 
31 
Administration (FDA) for the treatment of Type 1 diabetes. Using any of these medications 
32 
previously will not change your eligibility status for the study. 
33 
 
34 
This multi-center study will enroll up to 75 patients with T1D with A1c values between 6.5 to 
35 
10%. You will be randomized (similar to flipping a coin) in 1:1 fashion to either inhaled or 
36 
injectable insulin. If you are randomized into the injectable insulin group, you will continue 
37 
using your usual insulin dose before meals. If you are randomized into the inhaled insulin group, 
38 
you will be instructed to dose before meals and take necessary corrections at 1- and 2-hours after 
39 
meals. There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 
40 
phone visits). There will be a 4-week treatment comparison between the two groups and a 1-
41 
week post-study follow-up phone call. You will have blood drawn for standard lab tests (A1c, 
42 
complete metabolic panel {CMP}, complete blood count {CBC}) at the screening visit. 
43 
 
44 
You will be asked to use a real-time continuous glucose monitor (CGM) (Dexcom G5®, San 
45 
Diego, CA), which will be provided at the randomization visit for your day-to-day diabetes care. 
46 
CGM data will be downloaded at every clinic visit on a secured computer. The data will be 
47 


 
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Page 3 of 15 
Subject Initials 
 
analyzed after the study. You will be allowed to keep the CGM after the study is over for your 
1 
day-to-day diabetes care. 
2 
 
3 
Medications and device(s) that will be used in this study 
4 
 
5 
Technosphere insulin ( Afrezza®) 
6 
 
7 
Technosphere insulin (TI), inhaled insulin, (MannKind Corporation, Valencia, CA) is a dry 
8 
powder formulation of regular human insulin adsorbed onto technosphere micro particles for oral 
9 
inhalation. Inhaled insulin is currently approved for the treatment of Type 1 and 2 diabetes. 
10 
Hypoglycemia is a potential risk of taking any insulin including inhaled insulin therapy. Typical 
11 
symptoms of mild/moderate hypoglycemia include: cold sweats, cool pale skin, nervousness or 
12 
tremor, anxious feeling, unusual tiredness or weakness, confusion, difficulty concentrating, 
13 
drowsiness, excessive hunger, and/or transient vision changes. 
14 
 
15 
Using inhaled insulin in patients with chronic lung disease such as asthma or chronic obstructive 
16 
pulmonary disease (COPD) is not recommended by the FDA. Using inhaled insulin in patients 
17 
with asthma and COPD may cause worsening of respiratory symptoms. Patients with a chronic 
18 
lung problem will not be allowed to participate in the study. While using inhaled insulin, it is 
19 
recommended to check lung function with a small device called a spirometry every 6 months. 
20 
However, as a precaution for your safety, you will have 3 spirometry tests during the 6-week 
21 
period study (at screening, at 2-weeks of treatment, and at the end of the study). If there is more 
22 
than a 20% decrease in your lung function, you will be excluded from the study and advised to 
23 
stop using inhaled insulin as recommended by FDA and return to your previous insulin regimen. 
24 
Inhaled insulin causes a small decline (about 40 ml per drug label based on previous studies) in 
25 
lung function over time during therapy as measured by spirometry tests. For comparison, you 
26 
will receive spirometry tests regardless of the group that you are assigned. The most common 
27 
side effect is a temporary cough after inhaling the medication as seen with all inhaler 
28 
medications. 
29 
 
30 
Insulin aspart (Novolog®) 
31 
 
32 
Insulin aspart is an injectable rapid acting human insulin analog. It is currently approved for the 
33 
treatment of Type 1 and 2 diabetes. It is injected subcutaneously within 5-10 minutes before a 
34 
meal into the abdominal area, thigh, buttocks, or upper arm. 
35 
 
36 
Novolog® 100 units per mL (U-100) is available as a clear and colorless solution for injection in: 
37 
Novolog® FlexPen®. Injection site side effects may occur such as redness, tenderness, and very 
38 
rarely infection. 
39 
 
40 
Continuous glucose monitor (Dexcom®) 
41 
 
42 
Continuous glucose monitor is a device that monitors your blood sugar 24/7. The CGM includes 
43 
a receiver, a transmitter, and a sensor. It is a small attachment to your body with a small needle 
44 
insertion. This device requires calibration with finger stick blood sugar checks at least twice a 
45 
day. Every 7 days, the sensor of this device will need to be changed. The CGM will be inserted 
46 
by study staff, and you will be instructed on how to use the CGM and insert these sensors 
47 
yourself. This educational session may take 3-4 hours. You will also be instructed on completion 
48 


 
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Subject Initials 
 
of any medications, in an insulin diary which you will need to record with your meals and after-
1 
meals. You will need to write down all insulin that you had per day in your diary. Diaries will be 
2 
provided at the initial visit. 
3 
 
4 
The study protocol is registered with the NCT Government website: ClinicalTrials.Gov. 
5 
NCT03143816 
6 
 
7 
Research Study Selection 
8 
 
9 
You have been asked to participate in this research study because you are between 18-70 years of 
10 
age, you have type 1 diabetes that is moderately controlled, and you require both basal and 
11 
mealtime insulin to control your diabetes.  You must meet additional requirements in order to be 
12 
eligible for this study. 
13 
 
14 
If you are a woman, you must not be pregnant or breast feeding.  If you are a woman of 
15 
childbearing potential, you must also use adequate birth control methods or abstinence (no sexual 
16 
intercourse) during your participation in this study. 
17 
 
18 
It is important that you answer all of the screening questions completely.  You must disclose all 
19 
past and present diseases, allergies and all medications that you are taking, including prescription 
20 
and non-prescription drugs. 
21 
 
22 
Study Design 
23 
 
24 
You will be asked to participate in a 1-2 hour screening visit. In the same week, you will be 
25 
randomized into one of the two treatment groups during the baseline visit 2. The treatment group 
26 
will only use inhaled insulin for rapid acting insulin for meals and corrections. The control group 
27 
will only use injectable rapid-acting insulin for meals. If you are assigned to the control group, 
28 
you will be asked to continue to use your respective treatments for four weeks with no 
29 
predetermined change in dosage or titration. If you are assigned to the inhaled insulin group, you 
30 
will be asked to use inhaled insulin for meal coverage and for after-meal corrections at 1- and 2-
31 
hours after your main meals. Three main meals should be at least 4 hours apart from each other. 
32 
Because the duration of action of inhaled insulin is shorter than ultra-rapid insulin in onset 
33 
compared to injectable insulin, patients in the treatment group can use inhaled insulin for 
34 
correction dose(s) at 1-hour and 2-hour after the meal dose, if blood glucose (BG) is over 150 
35 
mg/dl. All patients in the treatment group will use a dose-conversion chart that will be provided 
36 
at the randomization for meals according to their baseline insulin calculation. All patients in the 
37 
treatment group will be given the option of using correction if BG at 1-hour after the meal is 
38 
between 150-200 mg/dl by 4 units of inhaled insulin, and if BG is over 200 mg/dl by 8 units of 
39 
inhaled insulin. If BG does not decrease more than 50 mg/dl, and/or still over 200 mg/dl at 2-
40 
hour after the meal, they will be given the option of using 4 units of inhaled insulin. All patients 
41 
in the treatment group will be instructed on proper use of inhaled insulin. Dose conversion from 
42 
injectable insulin to inhaled insulin and recommended after-meal correction doses will be 
43 
provided to you as a table. 
44 
 
45 
Other people in this study 
46 
 
47 
Up to 20 people from your area will participate in the study. 
48 


 
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Page 5 of 15 
Subject Initials 
 
 
1 
Up to 75 people around the United States will be in the study because this study is being 
2 
conducted at multiple sites. 
3 
 
4 
The Barbara Davis Center for Diabetes (BDC), primarily a leading T1D clinical and research 
5 
center equipped for large-scale clinical research, will enroll approximately 15-20 patients (Halis 
6 
Kaan Akturk, MD). The other four sites are: Atlanta Diabetes Associates (Bruce Bode, MD), 
7 
USC Westside Center for Diabetes (Anne Peters, MD), AMCR Institute (Timothy Bailey, MD), 
8 
and Rainier Clinical Research Center (Leslie Klaff, MD, and Ronald Brazg, MD).  
9 
 
10 
What happens if I join this study? 
11 
 
12 
If you join the study, you will be asked not to use acetaminophen or any acetaminophen-
13 
containing products during the continuous glucose sensor insertion period and for at least 24-
14 
hours before sensor insertion.  Use of acetaminophen-containing medications like Tylenol® 
15 
during sensor wear may affect device performance.  You will insert a sensor at least four times 
16 
during this study. 
17 
 
18 
Medications that affect blood sugar, including oral anti-diabetic medications and systemic 
19 
steroids also may not be used through the duration of the study. 
20 
 
21 
What are the study groups? 
22 
 
23 
There are two treatment groups. Beginning the day after visit 2, week 1, if you are in the inhaled 
24 
insulin treatment group, you will use only inhaled insulin for meals and after-meal corrections. If 
25 
you are in the control group, you will be using injectable insulin for meals as you use it in real 
26 
life. You will be provided with inhaled or injectable insulin and insulin for the duration of the 
27 
study. All basal insulin (Toujeo®, Lantus®, Basaglar®, Tresiba®) except NPH and detemir 
28 
(Levemir®) are allowed before and during the study as a part of MDI regimens. Basal insulin will 
29 
not be provided throughout the study period. 
30 
 
31 
You will be assigned into either the inhaled or injectable insulin group. You will be provided 
32 
with a CGM (Dexcom G5®, San Diego, CA) and six sensors for the duration of the study. You 
33 
will be allowed to keep the CGM system for your personal use after the study. The CGM data 
34 
will be downloaded and analyzed at all clinical visits. 
35 
 
36 
If you are a current smoker or have any other significant pulmonary disease, you will not be 
37 
allowed to participate in the study. No marijuana consumption will be allowed during the study 
38 
(since the effects of acute marijuana inhalations on inhaled insulin absorption are unknown). 
39 
 
40 
All oral anti-diabetic medications and other forms of insulin and injectable medications other 
41 
than mentioned in the protocol should not be taken in the last three months. Medications that 
42 
affect blood sugar, including oral anti-diabetic medications, are not to be used for the duration of 
43 
the study. You must not be taking inhaled or oral systemic corticosteroids. 
44 
 
45 
Screening, Visit 1 
46 
 
47 


 
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Subject Initials 
 
A screening visit: Visit 1 Informed consent will be obtained before starting any study-related 
1 
activities, 
2 
 
3 
During this visit, you will undergo a physical exam, EKG (heart rhythm test), vital signs, and 
4 
medical history, demographics, and any concomitant medications you take will be recorded. A 
5 
blood draw will be performed to assess for A1c (point of care preferred), CMP, and CBC. A 
6 
urine pregnancy test will be administered for females of childbearing potential. If you had a 
7 
qualified A1c done in the last two weeks, it will not be repeated at the screening visit unless the 
8 
study doctor deems it necessary. You will also receive a spirometry test for screening. 
9 
 
10 
This visit is expected to take 1-2 hours. 
11 
 
12 
You will be trained on study paperwork (food, glucose, and insulin diaries) during this visit.  
13 
You will be asked to continue checking blood glucose in the way you did before the study. 
14 
 
15 
Baseline/Randomization, Visit 2 (Week 0) ± 3 days: 
16 
 
17 
You will be randomized into one of two study groups and necessary study medication will be 
18 
dispensed. Instructions will be given on how to use the study medication, inhaled insulin, starting 
19 
the day following this visit with meals and corrections with doses recommended, and to basal 
20 
insulin regimen throughout the study without any dose change. However, the study doctor may 
21 
make necessary changes in your insulin dosages for your safety. Any changes that are done by 
22 
the study doctor out of the protocol for your safety will be recorded and considered in statistical 
23 
analysis. 
24 
 
25 
You will have your vital signs, weight, any adverse events, and current medications recorded. 
26 
You will start real-time CGM (Dexcom G5®, San Diego, CA) at that visit. You will be asked to 
27 
wear the CGM throughout the study. You will be allowed to keep the CGM after the study. You 
28 
will be trained to use the CGM, if you do not know how or if it is not part of your current 
29 
treatment plan. You will be trained on study paperwork (food, glucose and insulin diaries). You 
30 
will continue to check your blood glucose levels via finger stick as necessary. However, as 
31 
approved by the FDA, Dexcom G5® data may be used to take necessary action, but you must 
32 
calibrate the sensor two times a day per the label. 
33 
 
34 
If you are in the treatment group, you will be given the option of using correction if BG at 1-hour 
35 
after the meal is between 150-200 mg/dl by 4 units of inhaled insulin and if BG is over 200 
36 
mg/dl by 8 units of inhaled insulin. If BG does not decrease more than 50 mg/dl and/or still over 
37 
200 mg/dl at 2-hours after the meal, you will be given the option of using 4 units of inhaled 
38 
insulin. You will be asked to use the recommended conversion when you calculate your meal-
39 
time insulin based on your own insulin use. Since this is a real-life study, you will be instructed 
40 
to use inhaled insulin for after-meal correction for hyperglycemia; however, it will not be 
41 
mandated. If you are in the control group, you will be asked to continue your current injectable 
42 
insulin meal dose 15 minutes before meals according to your insulin dose. If you use the 
43 
correction, you will correct; however, you will not change your routine meal and after-meal 
44 
management. 
45 
 
46 
Telephone Visits (Visits 3, 5, and 7) ± 3 days 
47 
 
48 


 
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Subject Initials 
 
The study site staff will make a phone call to you at visits 3, 5, and 7. Although the window is ± 
1 
3 days, call time will be arranged in advance during your clinic visits. At these visits, study staff 
2 
will review any adverse events and changes in medications. Compliance to study protocol rules 
3 
and CGM use will be reviewed. 
4 
 
5 
Visit 4 (Week 2) ± 3 days: 
6 
 
7 
This visit will occur at Week 2. At Visit 4, study site staff will record your vitals, weight, review 
8 
of CGM data, and any adverse events and concomitant medications. Glucose download, insulin 
9 
use/dose, and sensor glucose data will be discussed with the study doctor or the study staff. 
10 
 
11 
You will remain in the same treatment or control group. Basal, bolus, and total daily dose of 
12 
insulin will be recorded. You will receive necessary refills for CGM supplies and study 
13 
medications. You will be reminded about the study protocol and insulin conversion and 
14 
correction doses. You will get a spirometry test. If your lung function declined more than 20% 
15 
after 2-weeks of treatment, you will be excluded and stop using inhaled insulin if you are in 
16 
inhaled insulin group. 
17 
 
18 
End of study, Visit 6 (Week 4) or Early Termination Visit ± 3 days: 
19 
 
20 
If you withdraw at any point during the study period, this visit will also be offered as an early 
21 
termination visit (ETV). 
22 
 
23 
If you have completed treatment,  you will schedule an end of study visit. This will be Visit 6 at 
24 
Week 4. During this visit, a physical exam will be conducted. Vitals, weight, review of CGM 
25 
data, adverse events, and concomitant medications will be recorded. Additional blood will be 
26 
drawn for A1c or point of care A1c will be done. Unused medication will be returned. Active 
27 
treatment with inhaled insulin will end at this visit. 
28 
 
29 
Basal, bolus, and total daily dose of insulin will be recorded. After the study, you will be 
30 
expected to continue your previous therapy. You will receive a spirometry test. 
31 
 
32 
What are the possible discomforts or risks? 
33 
 
34 
Lung Function Test (Spirometry): The Lung Function test requires you to blow hard into a 
35 
device. Some individuals may feel light-headed, dizzy, or short of breath after blowing hard. 
36 
These symptoms usually disappear without any treatment within a few minutes and can be 
37 
minimized or avoided if testing is done while subjects are in a sitting position. 
38 
 
39 
This test is a mechanical test and does not require any chemicals, radiation, or any other possible 
40 
hazardous material. 
41 
 
42 
All insulins lower blood sugar.  Like all insulins, inhaled insulin may lower your blood sugar too 
43 
much.  This is known as hypoglycemia.  Hypoglycemia may happen if too much insulin is taken 
44 
or you eat too little food and exercise too much compared to the amount of food you have eaten.  
45 
Low blood sugar may also happen when you drink alcohol, vomit and/or have diarrhea, or 
46 
change the type of your insulin.  If you have low blood sugar during the study, you may need to 
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take oral glucose (such as orange juice) or receive an intravenous (IV–through a vein) glucose 
1 
injection, which will cause your blood sugar to return to a safe level. 
2 
 
3 
Early warning signs of low blood sugar may be different from person to person or may be less 
4 
pronounced under certain conditions, such as a long history of diabetes; presence of diabetic 
5 
nerve disease; use of certain medicines such as beta-blockers; a change in insulin preparations; or 
6 
in some cases of improved control of diabetes.  
7 
 
8 
Signs of mild to moderate low blood sugar levels may happen suddenly and can include: 
9 
 
10 
• Sweating; dizziness; fast heart rate; shakiness; hunger; restlessness; tingling in the 
11 
hands, feet, lips or tongue; lightheadedness; feeling confused or unable to think; 
12 
headache; sleepiness or sleep problems; nervousness; unclear vision; unclear speech; 
13 
sadness; bad temper; unusual manners; shaky movement; and mood changes. 
14 
 
15 
Low blood sugar can make it hard to think or react.  You should not drive or use 
16 
mechanical equipment if you have a low blood sugar level.  If you do, you may harm 
17 
yourself or others. 
18 
 
19 
Low blood sugar can affect your heart and brain.  Severe low blood sugar can be dangerous and 
20 
may cause temporary or permanent harm to your heart or brain.  It may even cause 
21 
unconsciousness, seizures, or death. 
22 
 
23 
You may want to tell your family and friends that you are taking insulin and that there is a risk of 
24 
severe low blood sugar.  You may also want to tell them what the symptoms of severe low blood 
25 
sugar are, to help them recognize the symptoms if you develop them.  You may want to tell your 
26 
family and friends that they may need to give you oral (by mouth) glucose (such as orange juice) 
27 
or a glucagon injection.  In some cases, they may need to call for medical help to give you a 
28 
glucose injection to increase your blood sugar to a safe level. 
29 
 
30 
There is also the risk of high blood sugar called hyperglycemia.  High blood sugar may occur 
31 
when you have diabetes, even while you are on insulin.  It may happen when you have too much 
32 
sugar in your blood because you don’t have enough insulin.  High blood sugar can happen with:  
33 
 
34 
• Taking too little insulin or missing one or more doses.  
35 
• Too much carbohydrate intake (includes starchy foods, fruits and sweet foods and 
36 
drinks).  This can happen if you 1) eat larger meals 2) eat more often or 3) increase the 
37 
amount of carbohydrates in your meals.  
38 
• Some medicines may also change the effects of insulin.  Do not start any new medicines 
39 
until you speak with your own doctor to find out if they may affect your insulin dose.  
40 
• Certain medical conditions can affect insulin effects.  These medical conditions include 
41 
fever, infections, heart attacks, and stress.  These conditions usually require a temporary 
42 
increase in your insulin dose but you must discuss any changes in insulin dose with your 
43 
study doctor before increasing or decreasing the dose. 
44 
 
45 
High blood sugar can be mild to severe.  When your blood sugar is extremely high it can cause 
46 
very serious problems that need treatment right away.  Very high blood sugar can result in 
47 
unconsciousness and death. 
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1 
Often, high blood sugar does not show symptoms at all.  When high blood sugar does show 
2 
symptoms, they may include: 
3 
 
4 
• Confusion or sleepiness 
5 
• Increased thirst 
6 
• Decreased appetite, nausea, or vomiting 
7 
• Rapid heart rate 
8 
• Frequent urination and dryness in the mouth (too little fluid in your body) 
9 
• Fruity smelling breath 
10 
• Fast, deep breathing 
11 
• Pain in the stomach area. 
12 
 
13 
You may use inhaled insulin even when you are sick, including upper respiratory infections, such 
14 
as a common cold.  You should check your blood sugar more often when you are sick.  You may 
15 
need to change your insulin dose or you may be told to use injected insulin for a short time 
16 
during sickness. 
17 
 
18 
Risks of Having Blood Taken By Finger stick 
19 
 
20 
In this study you will need to get a few drops of blood from your finger.  To do this, you will 
21 
make a small prick on your finger and draw the blood onto a blood glucose meter test strip.  You 
22 
will feel a slight pain when the lancet pricks your finger.  Your fingertip may be sore for a day or 
23 
two. 
24 
 
25 
Risks of Having Blood Taken 
26 
 
27 
Over 6 weeks of this study (4-weeks of treatment, up to a week of screening, and a week later 
28 
follow up for possible side effects), we will need to get about 4 tablespoons of blood from you.  
29 
We will get blood by putting a needle into one of your veins and letting the blood flow into a 
30 
glass or plastic tube.  You may feel some pain when the needle goes into your vein.  A day or 
31 
two later, you may have a small bruise where the needle went under the skin. 
32 
 
33 
Risks of Wearing a Dexcom G5 CGM Sensor 
34 
 
35 
When the needle and G5 sensor are inserted, you might experience a sensation similar to an 
36 
insulin injection or the insertion of a pump infusion set.  After insertion, you may feel some 
37 
tenderness, but you should not feel any large amount of pain. 
38 
 
39 
Inflammation or redness, swelling, minor infection, and minor bleeding at the G5 sensor 
40 
insertion site are possible risks with use of the device.  In extremely rare cases, an infection 
41 
might spread to other parts of the body. 
42 
 
43 
Redness may occur where the adhesive pads are placed.  This will occur in most subjects and 
44 
will clear up on its own in about one to two days.  You may develop an allergic reaction to one 
45 
or more parts of the study device.  This is similar to allergies that occur due to medical tape or 
46 
jewelry.  Severe allergic reactions might involve swelling of the throat or tongue.  Severe allergic 
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reactions can be life threatening.  If you have an allergic reaction, seek emergency medical care 
1 
and call the study doctor as soon as possible. 
2 
 
3 
There is a chance that the G5 sensor or needle may break if not inserted right.  This would 
4 
require a minor procedure similar to removing a splinter.  If this happens, you should notify your 
5 
study coordinator as soon as possible. 
6 
 
7 
The radio waves that the study device puts out will not hurt you and you will not be aware of 
8 
them. 
9 
 
10 
The study may include risks that are unknown at this time. 
11 
 
12 
Only you can take the study drug.  It must be kept out of the reach of children and persons who 
13 
may not be able to read or understand the label. 
14 
 
15 
Your condition may not get better or may become worse during this study. 
16 
 
17 
Women who are pregnant or nursing a child may not participate in this study.  You must confirm 
18 
that, to the best of your knowledge, you are not now pregnant, and that you do not intend to 
19 
become pregnant during the study.  Before entering the study, you and the study doctor must 
20 
agree on the method of birth control you will use during the entire study.  If you suspect that you 
21 
have become pregnant during the study, you must notify the study doctor immediately.  Pregnant 
22 
women will be withdrawn from the study because the risks to the unborn fetus from the study 
23 
drug are not known. 
24 
 
25 
What are the possible benefits of the study? 
26 
 
27 
You may or may not benefit from being in this study.  This study is designed for the researcher 
28 
to learn more about the effects of the study insulins on your Type 1 diabetes and blood sugar 
29 
control. 
30 
 
31 
Will I have to pay for anything? 
32 
 
33 
You will not be charged for the study drug/device or any of the study procedures or office visits. 
34 
 
35 
Ask your study doctor to discuss the costs that will or will not be covered by the sponsor.  This 
36 
discussion should include the costs of treating possible side effects.  Otherwise, you might have 
37 
unexpected expenses from being in this study. 
38 
 
39 
Will I be paid for being in this study? 
40 
 
41 
You will be paid $50.00 each for visits 1, 2, 4 and 6. If you leave the study early, or if we have to 
42 
remove you from the study, you will be paid only for the visits you have completed.  You will be 
43 
paid $15.00 each for the telephone visits (Visits 3, 5, 7) for a total of up to $245.00. 
44 
 
45 
You will also be able to keep the Dexcom® G5® CGM receiver and transmitter units if you 
46 
complete the study. Study medications Afrezza® and Novolog ® will be provided free of charge 
47 
to you during the study. All CGM supplies with the device will be provided free of charge. 
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1 
Payment for participation in a study is taxable income. 
2 
 
3 
Are there alternative treatments? 
4 
 
5 
There may be other ways of treating your Type 1 diabetes.  These other ways include your 
6 
standard care regimen, such as different insulin products including the two study agents. 
7 
 
8 
You should talk to your doctor about your choices.  Make sure you understand all of your 
9 
choices before you decide to take part in this study.  You may leave this study and still have 
10 
these other choices available to you. 
11 
 
12 
Who is paying for this study? 
13 
 
14 
This research is being paid for by Mannkind Corporation., the manufacturer of the Technosphere 
15 
inhaled insulin. 
16 
 
17 
Is my participation voluntary? 
18 
 
19 
Taking part in this study is voluntary.  You have the right to choose not to take part in this study.  
20 
If you choose to take part, you have the right to stop at any time.  If you refuse or decide to 
21 
withdraw later, you will not lose any benefits or rights to which you are entitled. 
22 
 
23 
If you leave this study, you will still receive your normal medical care.  The only medical care 
24 
that you will lose is the medical care you are getting as part of this study.  You might be able to 
25 
get that same kind of medical care outside of the study.  Ask your study doctor if you would like 
26 
more information. 
27 
 
28 
What if there are new findings? 
29 
 
30 
You will be told if there are any new findings during the study that may affect whether you want 
31 
to continue to take part in the study.  You may be asked to sign a new consent form if this 
32 
occurs. 
33 
 
34 
Can I be removed from this study? 
35 
 
36 
The study doctor may decide to stop your participation without your permission if the study 
37 
doctor thinks that being in the study may cause you harm, or for any other reason.  Also, the 
38 
sponsor may stop the study at any time.  As a subject, you are free at any time to stop 
39 
participating in the study. 
40 
 
41 
What happens if I am injured or hurt during the study? 
42 
 
43 
If you have an injury while you are in this study, you should call Satish K. Garg, MD or Halis 
44 
Akturk, MD, immediately.  Their phone numbers are: (Garg) 303-724-6713 or 303-908-2132 (24 
45 
hours) and (Akturk) 303-724-0467. 
46 
 
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We will arrange to get you medical care if you have an injury that is caused by this research.  
1 
However, you or your insurance company will be billed for that care. 
2 
 
3 
If you are injured as a result of this study, you do not give up your right to pursue a claim 
4 
through the legal system. 
5 
 
6 
Who do I call if I have questions? 
7 
 
8 
Contact Satish K. Garg, MD at 303-724-6713 or 303-908-2132 (24 hours); Halis Akturk, MD at 
9 
303-724-0467 or 402-996-0040 (24 hours); for any of the following reasons: 
10 
 
11 
• If you have any questions about your participation in this study 
12 
• If at any time you feel you have had a research-related injury or a reaction to the study 
13 
drug 
14 
 
15 
Contact Christie Beatson, RD, CDE, study coordinator, at 303-724-6761 if you have questions, 
16 
concerns, or complaints about the research. 
17 
 
18 
If you have questions about your rights as a research subject or if you have questions, concerns, 
19 
or complaints about the research, you may contact: 
20 
 
21 
Western Institutional Review Board® (WIRB®) 
22 
1019 39th Avenue, SE 
23 
Puyallup, Washington 98374-2115 
24 
Telephone:  1 -800-562-4789 or 360-252-2500 
25 
E-mail:  Help@wirb.com 
26 
 
27 
OR 
28 
 
29 
Colorado Multiple Institutional Review Board (COMIRB) office at 303-724-1055. 
30 
 
31 
WIRB is a group of people who perform independent review of research under contract with the 
32 
University of Colorado Health Sciences Center. 
33 
 
34 
WIRB will not be able to answer some study-specific questions, such as questions about 
35 
appointment times.  However, you may contact WIRB if the research staff cannot be reached or 
36 
if you wish to talk to someone other than the research staff. 
37 
 
38 
Do not sign this consent form unless you have had a chance to ask questions and have received 
39 
satisfactory answers to all of your questions. 
40 
 
41 
If you agree to be in this study, you will receive a signed and dated copy of this consent form for 
42 
your records. 
43 
 
44 
Who will see my research information? 
45 
 
46 
The University of Colorado Denver and the hospital(s) it works with have rules to protect 
47 
information about you. Federal and state laws including the Health Insurance Portability and 
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Accountability Act (HIPAA) also protect your privacy. This part of the consent form tells you 
1 
what information about you may be collected in this study and who might see or use it.  The 
2 
institutions involved in this study include: 
3 
 
4 
Barbara Davis Center for Childhood Diabetes. 
5 
 
6 
Both the records that identify you and the consent form signed by you may be looked at by 
7 
others who have a legal right to see that information. 
8 
 
9 
• Federal offices such as the Office of Human Research Protection and the Food and Drug 
10 
Administration (FDA) that protect research subjects like you. 
11 
• People at the Colorado Multiple Institutional Review Board (COMIRB). 
12 
• People at the Western Institutional Review Board (WIRB). 
13 
• The study doctor and his/her team of researchers. 
14 
• Mannkind Corporation, who is the company paying for this research study. 
15 
• Officials at University of Colorado Denver, and officials at other institutions involved in 
16 
this study who are in charge of making sure that we follow all of the rules for research. 
17 
• An external trial observer center (CRO) 
18 
 
19 
Your information may be used and disclosed, to do the research, to study the results, and to make 
20 
sure that the research was done right. 
21 
 
22 
We might talk about this research study at meetings. We might also print the results of this 
23 
research study in relevant journals.  But we will always keep the names of the research subjects, 
24 
like you, private. 
25 
 
26 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
27 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
28 
Web site will include a summary of the results.  You can search this Web site at any time. 
29 
 
30 
You have the right to request access to your personal health information from the investigator.  
31 
To ensure proper evaluation of test results, your access to these study results may not be allowed 
32 
until after the study has been completed. 
33 
 
34 
We cannot do this study without your permission to see, use, and give out your information.  
35 
You do not have to give us this permission.  If you do not, then you may not join this study. 
36 
 
37 
We will see, use and disclose your information only as described in this form and in our Notice 
38 
of Privacy Practices; however, people outside the University of Colorado Denver and its affiliate 
39 
hospitals may not be covered by this promise and your information may be disclosed without 
40 
your permission. 
41 
 
42 
We will do everything we can to keep your records confidential. It cannot be guaranteed. 
43 
 
44 
The use and disclosure of your information has no time limit. You can cancel your permission to 
45 
use and disclose your information at any time by writing to the study’s Principal Investigator, at 
46 
the name and address listed below. If you do cancel your permission to use and disclose your 
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information, your part in this study will end and no further information about you will be 
1 
collected. Your cancellation would not affect information already collected in this study. 
2 
 
3 
Satish Garg, MD 
4 
University of Colorado Denver 
5 
Barbara Davis Center for Diabetes 
6 
1775 Aurora Court, MS A140 
7 
Aurora, CO 80045 
8 
 
9 
If you agree to be in this study, you will receive a signed and dated copy of this consent form for 
10 
your records. 
11 
 
12 
The investigator (or staff acting on behalf of the investigator) will also make all or some of the 
13 
following health information about you available to: Mannkind Corporation and the CRO. 
14 
 
15 
Information about you that will be seen, collected, used and disclosed in this study: 
16 
 
17 
• Name and Demographic Information (age, sex, ethnicity, address, phone number, etc. 
18 
• Portions of your previous and current Medical Records that are relevant to this study, 
19 
including but not limited to Diagnosis(es), History and Physical, laboratory or tissue 
20 
studies,  radiology studies, procedure results 
21 
• Research Visit and Research Test records 
22 
 
23 
What happens to Data, Tissue, Blood and Specimens that are collected in this study? 
24 
 
25 
Scientists at the University of Colorado Denver and the hospitals involved in this study work to 
26 
find the causes and cures of disease. The data, tissue, blood and specimens collected from you 
27 
during this study are important to this study and to future research. If you join this study: 
28 
 
29 
The data, or the tissue, blood, or other specimens are given by you to the investigators for this 
30 
research and so no longer belong to you. 
31 
 
32 
Both the investigators and any sponsor of this research may study your data, tissue, blood, or 
33 
other specimens collected from you. 
34 
 
35 
If data, tissue, blood, or other specimens are in a form that identifies you, UCD or the hospitals 
36 
involved in this study may use them for future research only with your consent or IRB approval. 
37 
 
38 
Any product or idea created by the researchers working on this study will not belong to you. 
39 
 
40 
There is no plan for you to receive any financial benefit from the creation, use or sale of such a 
41 
product or idea. 
42 
 
43 
You have the right to request access to your personal health information from the investigator.  
44 
To ensure proper evaluation of test results, your access to these study results may not be allowed 
45 
until after the study has been completed. 
46 
 
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If you agree to be in this study, you will receive a signed and dated copy of this consent form for 
1 
your records. 
2 
 
3 
Agreement to be in this study: 
4 
 
5 
I have read this consent form.  All of my questions have been answered.  I choose to be in this 
6 
study. 
7 
 
8 
By signing this consent form, I have not given up any of my legal rights. 
9 
 
10 
 
11 
 
 
12 
Subject Name (printed) 
13 
 
14 
CONSENT SIGNATURE: 
15 
 
16 
 
17 
 
 
 
 
18 
Signature of Subject 
Date 
19 
 
20 
 
21 
 
 
 
 
22 
Signature of Person Conducting Informed Consent Discussion 
Date 
23