Basal Insulin Glycemic ControL With DEglugec vs Aspart Via Pump: A Comparison of Insulin Degludec to Continuous Subcutaneous Infusion of Insulin Aspart for Basal Insulin Delivery in Type 1 Diabetes
Phase: PHASE4
Conditions: Type1 Diabetes Mellitus
Sponsor: Mountain Diabetes and Endocrine Center

V2.0, 7/13/2018 
1 
 
BIG LEAP: A comparison of insulin degludec to continuous subcutaneous infusion of insulin 
1 
aspart for basal insulin delivery in type 1 diabetes 
2 
Protocol Number: MDEC2018 
3 
INVESTIGATOR INITIATED STUDY PROPOSAL 
4 
Universal Trial Number: U1111-1199-8692 
5 
Mountain Diabetes and Endocrine Center 
6 
1998 Hendersonville Rd, Bldg 31 
7 
Asheville, NC, USA 
8 
 
9 
Correspondence to: 
10 
Wendy Lane MD 
11 
Director of Clinical Research 
12 
Mountain Diabetes and Endocrine Center 
13 
Phone: (828) 684- 9588 
14 
Cell: (828) 778-5006 
15 
Fax: (828) 684-9626 
16 
Email: mountaindiabetes@msncom 
17 
 
18 
BACKGROUND AND SIGNIFICANCE 
19 
 
20 
Physiologic insulin replacement for the treatment of type 1 diabetes, or intensive insulin 
21 
therapy, is administered either by multiple daily injections (MDI) of insulin or via continuous 
22 
subcutaneous insulin infusion (CSII) via insulin pump.  Since its inception in the 1970’s, CSII has 
23 
improved continuously in terms of both the devices and the rapid acting insulin analogues they 
24 
deliver so that today’s insulin pumps are considered the “gold standard” of intensive insulin 
25 
therapy. However, CSII has only shown advantages over MDI regimens which used older basal 
26 
insulin products including intermediate-acting insulin (NPH) and first generation insulin 
27 
analogues (glargine and detemir) including reducing the incidence of hypoglycemia, improving 
28 
overall glycemic control and improving glycemic variability (1,2).  CSII also has advantages in 
29 
terms of patient convenience and comfort by eliminating the need for multiple daily insulin 
30 
injections, portability of insulin, and the use of computerized bolus calculators to assist with 
31 
bolus calculations. However, patients treated with CSII continue to show significant glycemic 
32 
variability owing to different absorption characteristics of insulin infused subcutaneously at 
33 
different body sites and due to the inherent variability of absorption of rapid-acting insulin 
34 
analogues even when infused continuously in sub-unit quantities for basal insulin delivery by 
35 
modern insulin pumps.   
36 
Insulin degludec is a new ultralong-acting insulin analogue with a unique mechanism of 
37 
protraction giving it a flat, peakless pharmacodynamic profile with a coefficient of variation of 
38 
the glucose infusion rate of approximately 25% that of insulin glargine in glucose clamp studies 
39 

V2.0, 7/13/2018 
2 
 
and a half-life of 25 hours (3).  Insulin degludec has also been shown to have a reduced 
40 
incidence of hypoglycemia compared to insulin glargine in a head-to head clinical trial in 
41 
patients with type 1 diabetes. (4).  Whether insulin degludec might provide equivalent basal 
42 
insulin coverage with a flatter 24 hour glycemic profile compared to CSII using a rapid-acting 
43 
insulin analogue is currently not known as these have not been compared in a clinical trial.  Part 
44 
of the reason for this is because patients using CSII use a pump for both the basal and bolus 
45 
component of their insulin regimen; currently, no “bolus only” insulin delivery device exists.  
46 
Also, there was no compelling reason until now to study a hybrid model for basal/bolus insulin 
47 
regimens since there was no true 24 hour basal insulin product which had any therapeutic 
48 
advantage over basal insulin delivered by CSII.  Furthermore, it is now recognized that the use 
49 
of insulin infusion sets of various design in CSII lead to increased glucose variability by virtue of 
50 
local inflammation and micro-occlusions of the sets, which interfere with consistent insulin 
51 
basal delivery (5).  Insulin degludec, however, appears in clinical use to possibly have a flatter 
52 
glycemic profile than CSII can provide, with equivalent or even lower glycemic variability and 
53 
less hypoglycemia.  If so, patients with type 1 diabetes may achieve better overall glycemic 
54 
control with, and therefore prefer, a daily injection of insulin degludec for their basal insulin 
55 
needs in combination with their pump (with its bolus calculator) for their bolus insulin needs.   
56 
The purpose of this investigator-initiated trial is to compare the effect of a daily injection of 
57 
insulin degludec vs. basal insulin delivery via CSII, both in combination with bolus insulin 
58 
delivery via the patient’s usual insulin pump with insulin aspart, on glycemic variability, overall 
59 
blood glucose control and incidence of hypoglycemia, all assessed by continuous glucose 
60 
monitor (CGM), as well as patient satisfaction, in patients with type 1 diabetes currently using 
61 
CSII. 
62 
SPECIFIC OBJECTIVES 
63 
The primary objective of this trial is to determine whether insulin degludec will provide an 
64 
equally stable and consistent basal glycemic profile with lower glycemic variability as 
65 
determined by CGM compared to insulin aspart delivered by CSII in patients with type 1 
66 
diabetes experienced in use of insulin pump therapy.  Specifically, this study will determine if 
67 
the percent time in the target glycemic range (70 to 180 mg/dl) by CGM is superior using insulin 
68 
degludec than continuously infused insulin aspart, and if degludec is associated with lower GV 
69 
as assessed by the standard deviation (SD) of the mean daily glucose by CGM.  Particular 
70 
attention will be given to the nocturnal glucose profile (from midnight to 6 am) which most 
71 
closely reflects basal insulin action as it is typically the time of day least affected by bolus 
72 
insulin, food intake or exercise. Quality of life questionnaires regarding treatment preference 
73 
will be used to capture patient preference for method of basal insulin delivery. 
74 
RESEARCH DESIGN AND METHODS 
75 
Study hypothesis  
76 

V2.0, 7/13/2018 
3 
 
It is anticipated, based on the low glycemic variability of insulin degludec shown in glucose 
77 
clamp studies and seen in clinical practice, that insulin degludec will provide more stable 24 
78 
hour basal insulin action than insulin aspart by CSII in patients with type 1 diabetes.  
79 
OUTCOME MEASURES/SPECIFIC ENDPOINTS  
80 
 
81 
Primary endpoint  
82 
Percent time in euglycemia (BG 70 to 180 mg/dl) by CGM during the final 14 days of each 
83 
treatment period during steady state (with basal insulin delivery as either one daily injection of 
84 
insulin degludec or as insulin aspart via CSII). 
85 
 
86 
Key secondary endpoints 
87 
 
88 
1. SD of interstitial fluid glucose by CGM for 2 week period during each basal insulin 
89 
delivery method. (Note: because the Dexcom Platinum G5 CGM is currently only FDA 
90 
approved for 7 days of use, two contiguous CGM periods using 2 sensors, each for 7 
91 
days, will be performed to capture 2 weeks of continuous CGM data.) Dexcom G6 is 
92 
approved by FDA for 10 days of use so 2 sensors will be used during the CGM periods. 
93 
2. SD of blood glucose by CGM during the nocturnal period (midnight to 6 am) during each 
94 
basal insulin delivery method 
95 
 
96 
Other secondary endpoints 
97 
1. Percent time in hypoglycemia by CGM, captured at 2 levels of hypoglycemia: BG < 54 
98 
mg/dl (level 2) and BG  55-69 mg/dl (level 1), for each basal insulin treatment. 
99 
2. Percent time in normoglycemia (BG 70 to 140 mg/dl) by CGM during each basal 
100 
treatment period. 
101 
3. Time to recovery from level 2 hypoglycemia (BG >70 with resolution of symptoms) on 
102 
each treatment. If a second event (BG < 70 mg/dl) occurs within 60 minutes of a 
103 
previous hypoglycemic event, this will be considered part of the same hypoglycemic 
104 
episode. 
105 
4. Patient satisfaction by TRIM-D and TRIM-DD questionnaires with each basal insulin 
106 
treatment.  
107 
5. HbA1c after 20 weeks of each basal insulin treatment. 
108 
6. Total daily insulin dose, total basal insulin dose, and total bolus insulin dose on each 
109 
treatment. 
110 
 
111 
See Table 1:  Study Visit Table for study procedures at each visit and when specific endpoints 
112 
will be measured. 
113 
STUDY TYPE 
114 

V2.0, 7/13/2018 
4 
 
This will be a randomized, cross-over, open label, single-center study consisting of a 20 week 
115 
period on each of two basal insulin delivery methods, both in combination with insulin aspart 
116 
with boluses taken by insulin pump. Each 20 week period will consist of a 4 week insulin 
117 
optimization period for titration of basal and bolus insulin doses, followed by a 16 week 
118 
maintenance period.  The final 2 weeks of the maintenance period during each treatment arm 
119 
will be used for endpoint data collection.   The treatment sequence will occur in random order. 
120 
The study population will include patients with type 1 diabetes with good baseline glycemic 
121 
control who are experienced in the use of both CSII and CGM; the cross-over design allows each 
122 
subject to serve as his or her own control. 
123 
STUDY POPULATION  
124 
In order to confirm a 10% improvement in the time spent in euglycemia by CGM with 85% 
125 
power, 47 subjects will be studied.  Thus, between 55 and 60 subjects will be screened to allow 
126 
for a 10% drop-out rate. (See “Statistical Analysis Plan” for sample size calculation.) 
127 
INCLUSION CRITERIA 
128 
1. Male and female patients > 18 years of age with type 1 diabetes using CSII with any pump for 
129 
> 12 months. 
130 
2. Females must be using adequate contraception, defined as oral contraceptive pill, barrier 
131 
method of contraception, or surgical method (tubal ligation or hysterectomy). 
132 
3. Good glycemic control (HbA1c < 8.0%). 
133 
4. Patients are experienced in carbohydrate counting, evidenced by pump downloads showing 
134 
frequent meal boluses with realistic carbohydrate entries, few over-rides of the pump bolus 
135 
calculator, few to no omitted boluses (at least 3 boluses per day), and post-meal glucose levels 
136 
generally below 200 mg/dl indicating accurate carbohydrate assessment. 
137 
5. Patients are regular (>85% of time) users of the Dexcom G5 or G6 CGM. 
138 
6. Pump download confirms correct use of insulin pump features, including appropriate use of 
139 
bolus calculator with minimal overrides, entering carbohydrate content of meals, at least 3 
140 
boluses taken per day, appropriate use of correction boluses, and infusion set changes every 2 
141 
to 3 days. 
142 
7. No serious comorbidities including: retinopathy requiring active intervention, eGFR < 30, CV 
143 
event within the previous 6 months, active malignancy with ongoing treatment, any condition 
144 
requiring chronic use of systemic glucocorticoids, or any other condition which in the opinion of 
145 
the investigator would interfere with the subject’s ability to comply with the study protocol or 
146 
acutely affect insulin requirements. 
147 
8. Able to comply with study protocol. 
148 
9. Ability to provide written informed consent prior to any study-related procedures. 
149 
 
150 
EXCLUSION CRITERIA 
151 
 
152 
1. Subjects with type 2 diabetes. 
153 
2. Subjects with HbA1c > 8.0% 
154 

V2.0, 7/13/2018 
5 
 
3. Subjects not using CSII and CGM (ie, on MDI) 
155 
4. Subjects inexperienced in the use of CSII, or whose pump download shows poor 
156 
utilization of bolus calculator features, ie fewer than 2 boluses per day, lack of 
157 
correction boluses, frequent overrides of the recommended boluses, unrealistic 
158 
carbohydrate entries (suggestive of under-bolusing), not changing infusion set at least 
159 
every 3 days, or other evidence of poor insulin pump usage. 
160 
5. Subjects inexperienced in or not regular users (>85% of time) of Dexcom G5 or G6 CGM 
161 
6. Subjects who are using a Medtronic pump with low blood glucose suspend who are 
162 
unwilling to use the Dexcom CGM or to disengage the low blood glucose suspend 
163 
feature of the pump. 
164 
7. Use of any other CGM than Dexcom G5 or G6. 
165 
8. Serious concomitant illness. 
166 
9. Females unwilling to use adequate contraception, intending to become pregnant, or 
167 
breastfeeding. 
168 
10. Known or suspected allergy to study products, their excipients or related products. 
169 
11. Previous participation in this trial. Note: subjects who screen fail because of A1c may 
170 
rescreen once if, in the opinion of the investigator, the HbA1c was explainable (ie, 
171 
recent steroid injection or illness, etc) and atypical for the subject. 
172 
12. Hypoglycemic unawareness. 
173 
13. Episode of severe hypoglycemia (requiring assistance for treatment) within the previous 
174 
90 days. 
175 
 
176 
WITHDRAWAL CRITERIA 
177 
Subjects may withdraw at will for any reason. 
178 
Females who become pregnant will be discontinued from the study. 
179 
Subjects who do not comply with CGM use or switch from use of CSII to MDI will be 
180 
discontinued. 
181 
 
182 
Subjects who are discontinued from the study will not be replaced. 
183 
 
184 
RATIONALE FOR THE STUDY POPULATION 
185 
 
186 
A population of well controlled patients with type 1 diabetes who are experienced in the use of 
187 
both CSII and CGM was chosen in order to assess the effect of the change in glycemic profile 
188 
using two different methods of basal insulin delivery.  Studying a population with expertise in 
189 
diabetes self-management with these devices will minimize the effect of incorrect device use 
190 
and allow assessment of the effect of the change of insulin regimen itself.  Allowing the subjects 
191 
to use their insulin pumps for bolus insulin delivery, as they are accustomed, will minimize the 
192 
chances of skipping meal boluses and correction doses.  
193 
 
194 
Replacing basal insulin delivery by CSII with a single daily injection of degludec will add minimal, 
195 
if any, treatment burden which will be offset by potential therapeutic benefits.  These benefits 
196 
include the potential for reduced glycemic variability and the elimination of the risk of 
197 

V2.0, 7/13/2018 
6 
 
hyperglycemia and DKA with basal insulin interruption which can occur with infusion set 
198 
occlusion or dislodgement inherent to CSII. Subjects may also enjoy the freedom afforded by a 
199 
basal insulin injection which will allow them to disconnect from their pumps safely without 
200 
sacrificing glycemic control for prolonged periods of time (which is not an option using CSII for 
201 
basal insulin delivery). 
202 
 
203 
 
204 
VISIT PROCEDURES 
205 
 
206 
Please see pages 16-18 for “Visit Procedures”, which describes a detailed list of procedures and 
207 
assessments at each visit, and page 19 for the “Study Flow Sheet”, which summarizes study-
208 
related procedures at each visit in spreadsheet format. 
209 
 
210 
ASSESSMENTS OF EFFICACY 
211 
 
212 
Primary endpoint  
213 
Percent time spent in euglycemia by CGM: data will be downloaded from the Dexcom G5 or G6 
214 
(either by download of receiver or from Dexcom Clarity cloud-based application); this will yield 
215 
the percent time in euglycemia, hyperglycemia, hypoglycemia and SD for endpoint analyses. 
216 
 
217 
Other endpoints 
218 
1. HbA1c: This will be measured by central laboratory (LabCorp, Burlington, NC). 2. GlycoMark 
219 
(1,5 anhydroglucitol) will be measured by commercial assay (LabCorp, Burlington, NC).  All 
220 
laboratory specimens will be drawn and processed by site staff and shipped under required 
221 
conditions to LabCorp by courier with pick-up daily.  GlycoMark is a marker of glycemic 
222 
variability which essentially reflects postprandial glucose control.  It will be captured as a safety 
223 
measure to ensure that change of method of basal insulin delivery does not impact 
224 
postprandial glucose control in any way, since patients using CSII may on occasion have 
225 
increased postmeal basal insulin infusion rates (to compensate for inadequate mealtime insulin 
226 
dosing) which cannot be reproduced in the degludec treatment arm. 
227 
 
228 
ASSESSMENTS OF SAFETY: 
229 
 
230 
Hypoglycemia will be captured by fingerstick BG and by CGM. All episodes of severe 
231 
hypoglycemia (requiring assistance) will be documented and reported as AE’s in diaries.  
232 
Categories of hypoglycemia that will be captured include: percent time in two categories of 
233 
hypoglycemia (BG < 54 mg dl and 55-69 mg/dl) by CGM, episodes of symptomatic BG-confirmed 
234 
hypoglycemia (<54 mg/dl), nocturnal hypoglycemia and severe hypoglycemia. In the event 
235 
where the SMBG and the CGM readings are discordant, the SMBG will be considered the 
236 
primary source. 
237 
 
238 
Time to recovery from hypoglycemia, defined as BG > 70 with resolution of symptoms, during 
239 
each treatment will also be captured. 
240 
 
241 

V2.0, 7/13/2018 
7 
 
OTHER ASSESSMENTS 
242 
 
243 
Patient satisfaction with each study treatment will be assessed by TRIM-D and TRIM-DD 
244 
questionnaires.   
245 
 
246 
ASSESSMENT OF SUBJECT COMPLIANCE 
247 
 
248 
Compliance of study subjects with use of CSII and CGM will be assessed by review of device 
249 
downloads which capture percent time devices are used, set changes, boluses and 
250 
carbohydrate intake.  Since subjects will be using their insulin pumps to bolus, all bolus insulin 
251 
doses and carbohydrate intake will be captured in both treatment arms by review of insulin 
252 
pump downloads at each study visit. 
253 
 
254 
Compliance with administration of basal insulin during the degludec treatment arm will be 
255 
assessed by documentation of insulin doses and times in subject diaries. Number of missed 
256 
injections will be captured during the degludec treatment arm; number of infusion set changes, 
257 
set occlusions, and missed boluses will be captured during both treatment arms. 
258 
 
259 
STATISTICAL CONSIDERATIONS 
260 
 
261 
Sample Size Determination 
262 
The subjects in a recent study (4) should closely reflect the population we are going to study. 
263 
Using the statistics from that source as an estimate of population parameters, power analyses 
264 
were done for: (1) percent time in euglycemia (BG 70 to 180 mg/dl), desired effect size 0.4, (2) 
265 
SD of BG by CGM, desired effect size 0.44, and (3) HbA1c, desired effect size 0.44. The repeated 
266 
independent variable is degludec vs CSII. These a priori analyses – using G*Power, version 
267 
3.1.9.2 http://www.gpower.hhu.de/en.html – assumed a Type I error of .05 and a power of .85 
268 
(Type II error of .15).  
269 
 
270 
The sample size estimate required for percent time in euglycemia was the largest at n = 47. 
271 
Allowing for a 10% dropout rate a final sample size of 53 will be sought – more if possible. 
272 
 
273 
Statistical Methods 
274 
 
275 
Ho: For Type 1 DM subjects using degludec vs CSII, there is no difference between mean 
276 
percent time in euglycemia, mean SD of BG by CGM, or mean HbA1c.  
277 
 
278 
Ha: For Type 1 DM patients using degludec vs CSII, there will be mean differences between 
279 
percent time in euglycemia, SD of BG by CGM, and HbA1c. (No one tailed tests are planned.) 
280 
 
281 
Dependent Variable 
282 
One group of patients will first use degludec for 20 weeks then switch to CSII for 20 weeks. As 
283 
all eligible patients who sign the IRB consent form are identified, a random number will be 
284 

V2.0, 7/13/2018 
8 
 
generated to determine the treatment with which they begin first. The other group of patients 
285 
will start with CSII and after 20 weeks switch to Tresiba for 20 weeks. Randomization sequence 
286 
will be determined by computerized randomization program.  All patients will receive both 
287 
treatments unless they drop out. Dropouts are unlikely since the participants are all regular 
288 
continuing patients of the site’s clinical practice. 
289 
 
290 
Since each patient will be measured twice - insulin degludec vs CSII by pump – this repeated 
291 
measure will be the dependent variable. 
292 
Since study participants are all ongoing patients of the three physicians at the site, there should 
293 
be no missing data, per-protocol, or intention-to-treat issues. Only patients who complete the 
294 
entire 46-week study will be used in the final analysis. 
295 
 
296 
No continuous or ratio variables will be categorized. 
297 
 
298 
No interim analysis will be performed. 
299 
 
300 
Control/covariate variables 
301 
These will be recorded at the beginning of the study to help reduce error variance in the 
302 
dependent measures: 
303 
1) Time elapsed since diagnosis of Type 1 DM (ratio variable) 
304 
2) Age (ratio variable) 
305 
3) Physician attending each patient – there are 3 physicians (nominal). 
306 
4) Whether each patient started with CSII by pump or insulin degludec (nominal) 
307 
5) Race of patient (if there is any variability; unlikely) (nominal). 
308 
 
309 
Statistical Analysis 
310 
Statistical analyses will be performed using STATA version 15.0, revision 25, released 
311 
September 2017. (www.stata.com) 
312 
Since all the dependent variables are interval and the independent and control/covariate 
313 
variables are a mixture of ratio and nominal, a General Linear Model for Repeated Measures 
314 
analysis can be used. Depending on the final sample sizes a hierarchical stepwise analysis could 
315 
be performed to identify the more useful control/covariate variables. 
316 
DATA HANDLING AND RECORD KEEPING 
317 
The study data (CGM data and laboratory endpoints including HbA1c and GlycoMark) will be 
318 
uploaded and stored in the cloud in HIPAA-compliant electronic files.  Pertinent data for 
319 
endpoint safety and efficacy analyses will be entered into and electronically filed in password-
320 
protected Excel spreadsheets.  Hypoglycemia diaries will be on paper and stored as source 
321 
documents along with paper CRF’s capturing study-related procedures (history, physical exam, 
322 

V2.0, 7/13/2018 
9 
 
vital signs, con meds, AE’s) at each visit.  Patients will complete TRIM-D and TRIM-DD 
323 
questionnaires, and responses will be tabulated into Excel spreadsheets for statistical analysis. 
324 
All paper source documents and CRFs will be stored on site. All electronic data will be stored in 
325 
the cloud in HIPAA-compliant electronic files. 
326 
ETHICAL CONSIDERATIONS 
327 
The sponsor (Mountain Diabetes and Endocrine Center), its investigators and site staff will 
328 
comply with all applicable regulatory and legal requirements, ICH GCP guidelines and the 
329 
Declaration of Helsinki in obtaining and documenting the informed consent. 
330 
Informed consent will be obtained by a medically qualified site member (MD or RN) after each 
331 
subject has had time to review the informed consent document and have any questions about 
332 
the study answered.  This is performed in a conference room at the study site in a private and 
333 
unhurried fashion.  The subjects may bring family members with them to witness the informed 
334 
consent process.  The informed consent documents will be paper documents that will be 
335 
retained at the site, signed by the subject and investigator, and a copy will be provided to each 
336 
subject. 
337 
Upon approval of the study protocol, the study will be submitted for approval to IntegReview 
338 
IRB in Austin, Texas for review and approval.  The informed consent document will include 
339 
information about the IRB and contact information for the IRB, the site, and the study principal 
340 
investigator. 
341 
The study will be conducted in accordance with ICH GCP guidelines and the Declaration of 
342 
Helsinki. 
343 
STUDY SCHEDULE 
344 
Planned recruitment period: 6 to 9 months 
345 
Expected milestones: Start of study: immediately upon IRB approval (March 2018) 
346 
First patient first visit (FPFV): within 1 week of IRB approval (site is ready to begin recruitment 
347 
with subjects available to start upon protocol and IRB approval and obtaining study insulin) 
348 
Last patient first visit (LPFV): within 6 to 9 months of FPFV 
349 
Last patient last visit: 46 weeks after LPFV 
350 
Estimated study duration (FPFV to LPLV): 14 months (March 2018 to May 2019) 
351 
Completion of final study report: within 6 weeks of study completion 
352 
Time to submission of study for publication: within 12 weeks of study completion 
353 
STUDY DRUGS AND MATERIALS 
354 

V2.0, 7/13/2018 
10 
 
Study medication: insulin degludec (Tresiba) U100 or insulin degludec (Tresiba) U200 (Novo 
355 
Nordisk) with insulin aspart (administered as bolus insulin via insulin pump) (Novolog, Novo 
356 
Nordisk) for one treatment arm; insulin aspart (Novolog) administered by CSII for both basal 
357 
and bolus insulin in second treatment arm.  
358 
Study Devices: subjects’ own insulin pumps will include Medtronic (530, 730 models; no low 
359 
blood glucose suspend models or closed loop pumps will be used), Animas Ping, Animas Vibe, 
360 
Tandem T-slim and Insulet Omnipod. 
361 
The study CGM will be Dexcom G5 or G6. 
362 
PACKAGING AND LABELLING OF STUDY MEDICATION AND DEVICES 
363 
Study insulins (insulin degludec and aspart) will be distributed at study visits to each subject 
364 
from the site.  Insulin degludec will be supplied in injection pens (5 per box for U100 and 3 per 
365 
box for U200).  Insulin aspart will be supplied in vials (as bolus insulin will be administered via 
366 
insulin pump.) Subjects will use their own insulin pumps and pump supplies during the study.  
367 
Dexcom sensors will be supplied for a two week period (using one sensor weekly) at baseline 
368 
and for the final two weeks of each treatment period.  These will be distributed and placed at 
369 
CGM dispensing/insertion site visits (see study visit flow sheet). 
370 
STORAGE AND DRUG ACCOUNTABILITY OF STUDY MEDICATION 
371 
Study insulins will be received in temperature-controlled containers and the temperature of the 
372 
medication upon receipt will be recorded.  Study insulins will be stored at the study site in 
373 
refrigerators maintained between 2 and 8 degrees Celsius; the temperature will be monitored 
374 
and recorded daily.  No trial medication will be dispensed to any individual not enrolled in the 
375 
study.  All medication used in the study will be recorded in the CRF at each study dispensing 
376 
visit.  Subjects will be provided with sufficient study insulin for study completion. 
377 
Subjects will be instructed not to refrigerate opened insulin degludec (Tresiba U100 & U200) 
378 
and to store the product at room temperature.  Properly stored opened insulin degludec can be 
379 
used for up to 8 weeks (7).  Subjects may choose to refrigerate or not refrigerate an opened vial 
380 
of insulin aspart (Novolog), maintaining the vial at a temperature of less than 86°F (30°C) for up 
381 
to 4 weeks (8). 
382 
AUXILIARY SUPPLY 
383 
Study subjects will use their own insulin pumps and insulin pump supplies. 
384 
Dexcom glucose sensors (6 per subject) will be purchased by the site and supplied to subjects 
385 
for two weeks at 3 times (baseline and for the final two weeks of each treatment period).  
386 
Subjects will use their own CGM receiver devices which will be downloaded at appropriate 
387 
study visits.  Site will have back up receivers to supply to subjects in case of loss or malfunction 
388 
of subject’s own device (not likely).  Subjects will use their own sensors for each treatment 
389 
period except for the 3 two week periods of CGM data capture as described above. 
390 

V2.0, 7/13/2018 
11 
 
 
391 
 
392 
RANDOMIZATION AND BLINDING 
393 
This is an unblinded study as the two basal insulin delivery methods (degludec via injection vs. 
394 
aspart via CSII) cannot be blinded. For a description of the randomization and treatment 
395 
allocation, please refer to the Statistical Methods section above.  
396 
CONCOMITANT ILLNESSES AND MEDICATIONS 
397 
Definitions: 
398 
Concomitant illness: any illness that is present at the start of the trial (at the first study visit). 
399 
Concomitant medication: any medication other than the trial product(s) that is taken during the 
400 
trial, including the screening and run-in periods. 
401 
Details of all concomitant illnesses and medication will be recorded at trial entry (at the first 
402 
study visit). Any changes in concomitant medication will be recorded at each visit.  
403 
The information collected for each concomitant medication will include start date, stop date or 
404 
continuing, and indication. 
405 
For each concomitant illness, date of onset, date of resolution or continuing, will be recorded. 
406 
 
407 
ADVERSE EVENTS 
408 
 
409 
Adverse events will be captured at each study visit and recorded on CRF’s.  Special AE and SAE 
410 
reporting forms have been created to capture these events.  SAE’s will be reported within 24 
411 
hours of discovery to appropriate local and federal authorities as well as to the IRB when 
412 
appropriate.  The study site will comply with all local legal, regulatory, and IntegReview IRB 
413 
requirements.  
414 
Mountain Diabetes and Endocrine Center, its investigators, and site staff will be responsible for 
415 
reporting of all adverse events including serious adverse events (SAE), suspected unexpected 
416 
serious adverse reactions (SUSARs) and serious adverse drug reactions (SADRs) to the 
417 
competent authority and independent ethics committee/institutional review board based upon 
418 
federal regulations and local/IRB policies.  
419 
Mountain Diabetes and Endocrine Center, its investigators, and site staff will report to Novo 
420 
Nordisk all SAEs, SUSARs, and SADRs at the same time such events are reported to regulatory 
421 
authorities or within 15 days from the site becoming aware of such adverse events, whichever 
422 
comes first.  
423 
Mountain Diabetes and Endocrine Center, its investigators, and site staff will collect the 
424 
following information at minimum for each of these events: 
425 
1. Study name 
426 
2. Patient identification  
427 

V2.0, 7/13/2018 
12 
 
3. Event (with appropriate diagnosis) 
428 
4. Drug  
429 
5. Reporter identification  
430 
Also 6) Causality, and 7) Outcome might be reported, if appropriate. 
431 
DEFINITIONS 
432 
Adverse Event (AE): 
433 
An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not 
434 
related to the trial product(s). This includes events reported from the first trial related activity 
435 
after the subject has signed the informed consent and until post treatment follow-up period as 
436 
defined in the protocol.  This will also include any events related to the malfunction of a 
437 
medical device (i.e. an insulin pump or Dexcom CGM).  The following will not be recorded as 
438 
AEs, if recorded as medical history/concomitant illness on the CRF at screening: 
439 
• Pre-planned procedure, unless the condition for which the procedure was planned has    
440 
worsened from the first trial related activity after the subject has signed the informed consent 
441 
• Pre-existing conditions found as a result of screening procedures  
442 
Clinical Laboratory Adverse Event: 
443 
A clinical laboratory AE is any clinical laboratory abnormality regarded as clinically significant, 
444 
i.e. an abnormality that suggests a disease and/or organ toxicity and is of a severity which 
445 
requires active management, (i.e. change of dose, discontinuation of trial product, more 
446 
frequent follow-up or diagnostic investigation). 
447 
 
448 
Serious Adverse Event (SAE): 
449 
A serious AE is an event that results in any of the following: 
450 
• Death 
451 
• A life-threatening* experience 
452 
• In-patient hospitalization or prolongation of existing hospitalization 
453 
• A persistent or significant disability/incapacity 
454 
• A congenital anomaly/birth defect 
455 
• Important medical events that may not result in death, be life-threatening*, or require 
456 
  hospitalization may be considered an SAE when, based upon appropriate medical judgement, 
457 
they may jeopardise the subject and may require medical or surgical intervention to prevent 
458 
one of the outcomes listed in this definition.  Suspicion of transmission of infectious agents 
459 
must always be considered an SAE. 
460 
*The term life-threatening in the definition of SAE refers to an event in which the subject was at risk of death at 
461 
the time of the event. It does not refer to an event which hypothetically might have caused death if it was more 
462 
severe. 
463 
 
464 
Suspected Unexpected Serious Adverse Event (SUSAR):  
465 
Mountain Diabetes and Endocrine Center will inform the appropriate regulatory authorities, the 
466 
IRB, and Novo Nordisk of trial product-related SUSARs in accordance with reporting 
467 
requirements and GCP guidelines. 
468 

V2.0, 7/13/2018 
13 
 
 
469 
Serious Adverse Drug Reaction (SADR):  
470 
An adverse drug reaction (ADR) is an adverse event for which a causal relationship 
471 
(Possible/Probable relation) between the study drug and the occurrence of the event is 
472 
suspected. The ADR will be classified as serious if it meets one or more of the seriousness 
473 
criteria.  
474 
 
475 
Medical Events of Special Interest (MESI): A MESI is (1) a medication error (e.g. wrong drug 
476 
administration or wrong route of administration) or (2) a suspected transmission of an 
477 
infectious agent via the product 
478 
 
479 
Non-Serious Adverse Event: 
480 
A non-serious AE is any AE which does not fulfill the definition of an SAE. 
481 
 
482 
Severity Assessment Definitions: 
483 
• Mild: Transient symptoms, no interference with the subject’s daily activities 
484 
• Moderate: Marked symptoms, moderate interference with the subject’s daily activities 
485 
• Severe: Considerable interference with the subject’s daily activities, unacceptable 
486 
 
487 
Relationship to study medication Assessment Definitions:  
488 
• Probable: Good reason and sufficient documentation to assume a causal relationship 
489 
• Possible: A causal relationship is conceivable and cannot be dismissed 
490 
• Unlikely: The event is most likely related to an etiology other than the trial product 
491 
 
492 
Outcome Categories and Definitions: 
493 
 
494 
• Recovered: Fully recovered or by medical or surgical treatment the condition has returned to 
495 
the level observed at the first trial related activity after the subject signed the informed 
496 
consent 
497 
• Recovering: The condition is improving and the subject is expected to recover from the event. 
498 
This term should only be used when the subject has completed the trial 
499 
• Recovered with sequelae: As a result of the AE, the subject suffered persistent and     
500 
significant disability/incapacity (e.g. became blind, deaf, paralysed). Any AE recovered with 
501 
sequelae will be rated as an SAE 
502 
• Not recovered 
503 
• Fatal 
504 
• Unknown 
505 
 
506 
Collection, Recording, Evaluating, and Reporting of Adverse Events 
507 
 
508 
All events meeting the definition of an adverse event will be collected, reported, and evaluated 
509 
from the first trial-related activity after the subject has signed the informed consent and until 
510 
the end of the post-treatment follow-up period as stated in the protocol. All adverse events 
511 

V2.0, 7/13/2018 
14 
 
resulting from incorrect storage or usage of study product as per product labelling, if applicable, 
512 
will be reported to the appropriate institutions (7,8).  The investigator will copy Novo Nordisk 
513 
when expediting SAE information to health authorities and will report all SAEs related to Novo 
514 
Nordisk products to the local Novo Nordisk affiliate safety department.  SAE submission to 
515 
Novo Nordisk will be within 15 days from the investigator’s first awareness of the event.  
516 
 
517 
Follow-up of Adverse Events 
518 
 
519 
During and following a subject’s participation in this clinical trial, Mountain Diabetes and 
520 
Endocrine Center, its investigators and site staff, will provide adequate medical care to the 
521 
study subject for any study-related adverse events, including clinically significant laboratory 
522 
values related to the study. This medical care for study subjects will be provided regardless of 
523 
their insurance status. 
524 
 
525 
All adverse events classified as serious or severe or possibly/probably related to the trial 
526 
product will be followed until the subject has recovered and all queries have been resolved. 
527 
For cases of chronic conditions, follow-up until the outcome category is “recovered” is not 
528 
required, as these cases can be closed with an outcome of “recovering” or “not recovered”. 
529 
All other adverse events will be followed until the outcome of the event is “recovering” (for 
530 
chronic conditions), or “recovered” or until the end of the post-treatment follow-up stated in 
531 
the protocol, whichever comes first, and until all queries related to these AEs have been 
532 
resolved. 
533 
 
534 
Pregnancy 
535 
Study subjects will be instructed to notify the site and study physician immediately if they 
536 
become pregnant.  
537 
 
538 
Mountain Diabetes and Endocrine Center, its investigators and site staff, will report to Novo 
539 
Nordisk any pregnancy occurring during the trial period. Reporting of pregnancy by the site 
540 
will occur within the same timelines described above for reporting of Adverse Events.  
541 
  
542 
Pregnancy complications will be recorded as adverse event(s). If the infant has a congenital 
543 
anomaly/birth defect this must be reported and followed up as a serious adverse event. 
544 
 
545 
Precautions/ Insulin Over-dosage 
546 
Study subjects will be prescribed glucagon kits and treatment of hypoglycemia will be reviewed 
547 
with subjects upon enrolment into the study.  
548 
 
549 
LIABILITY AND SUBJECT INSURANCE: 
550 
During and following a subject’s participation in trial, Mountain Diabetes and Endocrine 
551 
Center and the study physicians will provide adequate medical care to the study subject for 
552 
any study-related adverse events, including clinically significant laboratory values related to 
553 

V2.0, 7/13/2018 
15 
 
the study. This medical care for study subjects will be provided regardless of their insurance 
554 
status. 
555 
 
556 
Mountain Diabetes and Endocrine Center and its investigators will be responsible for the 
557 
conduct of the study and agree to defend, indemnify, and hold harmless Novo Nordisk, any of 
558 
its parent companies, affiliates, or subsidiaries, and their respective officers, directors, 
559 
employees, agents, representatives, distributors, salespersons, customers, licensees, and 
560 
end-users from and against any claim, suit, demand, loss, damage, expense or liability 
561 
imposed by any third party arising from or related to: (a) any breach of sponsor-investigator's 
562 
obligations or representations; or (b) sponsor-investigator’s negligent or grossly negligent use 
563 
or willful misuse of the study drug, the results, or services derived therefrom.  This 
564 
indemnification shall not apply in the event and to the extent that a court of competent 
565 
jurisdiction or a duly appointed arbiter determines that such losses or liability arose as a 
566 
result of Novo Nordisk’s gross negligence, intentional misconduct, or material breach of its 
567 
responsibilities.  
568 
 
569 
EVALUABILITY OF SUBJECTS 
570 
Only the principal investigator has the authority to exclude any subjects or data observations 
571 
after the initiation of the study, initial selection of subjects, and beginning of data collection. 
572 
Possible reasons for such actions might be (1) questionable validity or reliability of data 
573 
collection or measurement techniques for a particular subject, (2) misrepresentation of initial 
574 
selection criteria by a subject, or (3) changes in the health conditions of subjects that might 
575 
affect the reliability or validity of measurements or accuracy of data collection procedures. The 
576 
reasons for any such action will be carefully documented by the principal investigator and kept 
577 
on file for the actionable subject. 
578 
 
579 
PREMATURE TERMINATION OF STUDY 
580 
 
581 
The study will only be discontinued prematurely in the unlikely event of an unforeseen safety 
582 
concern arising from the study protocol.   
583 
 
584 
PUBLICATION PLAN 
585 
 
586 
Upon approval, the study will be registered with www.clinicaltrials.gov. 
587 
 
588 
Upon study completion, the study results will be submitted in a manuscript to a peer-reviewed 
589 
journal.  It is anticipated that the study results will be of sufficient interest and importance to 
590 
be presented at one or more national meetings, notably ADA, AACE and AADE.   
591 
 
592 
REFERENCES 
593 
1. Miller KM et al. Diabetes Care 2015; 38: 971-978 
594 

V2.0, 7/13/2018 
16 
 
2. Misso ML et al. Cochrane Database Syst Rev. 2010(1):CD005103 
595 
3. Heise T et al. Diabetes Obes Metab 2012 Sep;14(9) 859-64 
596 
4. Lane W et al. JAMA. 2017; 318 (1): 33-44 
597 
5. Hauzenber JR et al. Diab Technol Therapeutics 2017 
598 
http://online.liebertpub.com/doi/full/10.1089/DIA.2017.0175 
599 
6. Bergenstal R et al.  JAMA. 2016; 316(13):1407-1408 
600 
7. Novo Nordisk. (2015). TRESIBA® (insulin degludec injection) Label. 28-29 
601 
8. Novo Nordisk. (2000). NovoLog (insulin aspart [rDNA origin]) injection label. 21-22 
602 
 
603 
APPENDIX: METHOD OF CONVERSION OF BASAL INSULIN BY CSII TO DEGLUDEC 
604 
 
605 
Upon randomization to insulin degludec, or upon crossover from CSII to insulin degludec, the 
606 
first dose of insulin degludec will be administered on day one and a 50% temporary basal 
607 
reduction of the insulin pump for 24 hours will be activated.  After 24 hours, the insulin pump  
608 
basal rate will be lowered to the lowest hourly infusion rate (0.025 units per hour or 0.05 units 
609 
per hour for a total daily basal insulin dose of either 0.6 or 1.2 units per day) for the duration of 
610 
the insulin degludec treatment arm, with the remainder of the basal insulin dose administered 
611 
as a single daily Tresiba injection. 
612 
 
613 
The 24 hour basal insulin dose by CSII will be converted to degludec on a unit-for-unit basis.  
614 
This is because both degludec and CSII are roughly equivalent methods with high efficiency 
615 
(bioavailability) for delivery of a basal insulin dose.  Although there are no head-to-head studies 
616 
comparing basal insulin dose by CSII to degludec, clinical studies (and the experience of the 
617 
investigator) suggest that the lowest basal insulin requirement for any given subject will be with 
618 
either CSII or degludec compared to glargine, NPH or detemir. 
619 
 
620 
A comparison of insulin degludec to continuous subcutaneous infusion of insulin aspart for 
621 
basal insulin delivery in type 1 diabetes: 
622 
 
623 
Visit Procedures 
624 
 
625 
Note: Assessment of hypoglycemia and capturing of AE’s (including technical complaints and 
626 
device site reactions) will be performed at each study visit, as well as diabetes education. 
627 
 
628 
Visit 1 (Screening Visit): Obtain written informed consent; review inclusion/exclusion criteria; 
629 
demography (including child bearing potential and tobacco use); medical history; record 
630 
concomitant medications; vital signs (incl. height); complete physical examination; review 
631 
download of Dexcom and pump; HbA1c, GlycoMark, CBC, comprehensive metabolic profile 
632 
(CMP), lipid panel, urine microalbumin/creatinine ratio (LabCorp); pregnancy test (urine); 
633 
review treatment of hypoglycemia; insert Dexcom sensor; provide a hypoglycemia/basal dose 
634 
diary 
635 
 
636 
Phone Visit 2: Remind subject to insert new Dexcom sensor; assessment of infusion site 
637 
reactions and occlusions; hypoglycemia assessment (insulin titration if required)  
638 

V2.0, 7/13/2018 
17 
 
 
639 
Visit 3 (Randomization): Review of inclusion/exclusion criteria; vital signs; CGM and insulin 
640 
pump downloads; HbA1c (POC - Afinion); insulin optimization/titration; dispensing of 
641 
hypoglycemia/basal dose diary; Tresiba pen teaching (degludec arm only); dispense trial 
642 
product; treatment questionnaires  
643 
 
644 
Visit 4: Vital signs; pump and CGM downloads; insulin optimization/titration; assessment of 
645 
infusion site reactions and occlusions; dispensing of hypoglycemia/basal dose diary  
646 
 
647 
Visit 5:  Vital signs; pump and CGM downloads; insulin optimization/titration; assessment of 
648 
infusion site reactions and occlusions; dispense trial product; dispensing of hypoglycemia/basal 
649 
dose diary; drug accountability and diabetes education. 
650 
 
651 
Phone Visit 6: Ensure subject is changing insulin pump sites and CGM per protocol, assessment 
652 
of infusion site reactions and occlusions; review of hypoglycemia (insulin titration if required)  
653 
 
654 
Visit 7: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
655 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
656 
accountability  
657 
 
658 
Phone Visit 8: Ensure subject is changing insulin pump sites and CGM per protocol, assessment 
659 
of infusion site reactions and occlusions; review of hypoglycemia (insulin titration if required)  
660 
 
661 
Visit 9: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
662 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
663 
accountability  
664 
 
665 
Visit 10: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
666 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
667 
accountability  
668 
 
669 
Visit 11: Dexcom sensor insertion; assessment of infusion site reactions and occlusions, review 
670 
of hypoglycemia/basal dose diary  
671 
 
672 
Visit 12 (Cross-over Visit): Vital signs; complete physical examination; pump and CGM 
673 
downloads; insulin optimization/titration; treatment crossover; Tresiba pen training (degludec 
674 
arm only); HbA1c, GlycoMark, CBC, comprehensive metabolic profile (CMP), urine 
675 
microalbumin/creatinine ratio (LabCorp); pregnancy test (urine); dispense trial product; 
676 
treatment questionnaires; dispensing of hypoglycemia/basal dose diary; assessment of infusion 
677 
site reactions and occlusions; drug accountability  
678 
 
679 
Visit 13: Vital signs; pump and CGM downloads; insulin optimization/titration; assessment of 
680 
infusion site reactions and occlusions; dispensing of hypoglycemia/basal dose diary  
681 
 
682 

V2.0, 7/13/2018 
18 
 
Visit 14: Vital signs; pump and CGM downloads; insulin optimization/titration; assessment of 
683 
infusion site reactions and occlusions; dispense trial product; dispensing of hypoglycemia/basal 
684 
dose diary; drug accountability 
685 
 
686 
Phone Visit 15: Ensure subject is changing insulin pump sites and CGM per protocol, assessment 
687 
of infusion site reactions and occlusions; review of hypoglycemia (insulin titration if required)  
688 
 
689 
Visit 16: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
690 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
691 
accountability  
692 
 
693 
Phone Visit 17: Ensure subject is changing insulin pump sites and CGM per protocol, assessment 
694 
of infusion site reactions and occlusions; review of hypoglycemia (insulin titration if required)  
695 
 
696 
Visit 18: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
697 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
698 
accountability  
699 
 
700 
Visit 19: Vital signs; pump and CGM downloads; assessment of infusion site reactions and 
701 
occlusions; dispense trial product; dispensing of hypoglycemia/basal dose diary; drug 
702 
accountability  
703 
 
704 
Visit 20: Dexcom sensor insertion; assessment of infusion site reactions and occlusions, review 
705 
of hypoglycemia/basal dose diary  
706 
 
707 
Visit 21 (End of study visit): Vital signs; complete physical examination; review download of 
708 
Dexcom and pump; HbA1c, GlycoMark, CBC, comprehensive metabolic profile (CMP), lipid 
709 
panel, urine microalbumin/creatinine ratio (LabCorp); pregnancy test (urine); review treatment 
710 
of hypoglycemia; insulin optimization for post-trial treatment; assessment of infusion site 
711 
reactions and occlusions; drug accountability; treatment questionnaires 
712 
 
713 
Phone Visit 22 (Follow-up phone visit): Capture AE’s; review of hypoglycemia 
714 
 
715 

V2.0, 7/13/2018 
19 
 
Trial Procedures 
Screen- 
ing 
 
Random-
ization 
Treatment Period 1 (First treatment group) 
Treatment Period 2 (Second treatment group) 
EOT 
F/U 
Visit (V), Phone (P) 
V1 
P2 
V3 
V4 
V5 
P6 
V7 
P8 
V9 
V10 
V11 
V12 
V13 
V14 
P15 
V16 
P17 
V18 
V19 
V20 
V21 
P22 
Timing of Visit (Weeks) 
-2 
-1 
0 
2 
4 
6 
8 
10 
12 
16 
18 
20 
22 
24 
26 
28 
30 
32 
36 
38 
40 
44 
Visit Window (Days) 
 
+ 2 
+ 1 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 2 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 3 
+ 2 
+ 3 
+ 3 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In/Exclusion Criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography & Tobacco 
Use 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Concomitant Illness 
/Medical History 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Child Bearing Potential 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test, Urine 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
Vital Signs 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
Dexcom Sensor Insertion 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
CGM Download 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
Insulin Pump Download 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
Insulin Optimization 
 
 
X 
X 
X 
 
 
 
 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Blood Sampling 
X 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Point-of-Care HbA1C 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HbA1C (central laboratory) 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
GlycoMark 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
CBC 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
CMP 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Lipids 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urine MA 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hypoglycemia 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Technical Complaints 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Infusion Site Reactions 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Infusion Site Occlusions 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispensing of Trial 
Product 
 
 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 
 
Drug Accountability 
 
 
 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
Treatment Crossover 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Questionnaires/Surveys 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
Diabetes Education 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
REMINDERS 
Attend Visit Fasting 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 

V2.0, 7/13/2018 
20 
 
Degludec Pen Instruction 
 
 
X* 
 
 
 
 
 
 
 
 
X* 
 
 
 
 
 
 
 
 
 
 
Hand out Hypo/Basal 
Dose Diary 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
 
 
* Dependent upon to which treatment group the subject is assigned.