Glycemic Control and Treatment Satisfaction Using Finesse Versus Pen for Initiating Bolus Insulin Dosing in Type 2 Diabetes Mellitus Patients Not Achieving Glycemic Targets on Basal Insulin With/Without Anti-Hyperglycemic Agents
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Sponsor: Calibra Medical, Inc.

NCT Number: NCT02542631
Document Date: 21-Sep-2015

STUDY PROTOCOL AND STATISTICAL ANALYSIS 
Title of Study 
Glycemic Control and Treatment Satisfaction Using Finesse 
Versus Pen for Initiating Bolus Insulin Dosing in Patients 
with Type 2 Diabetes Mellitus (T2DM) not Achieving 
Glycemic Targets on Basal Insulin With/Without Anti-
Hyperglycemic Agents (AHA) 
Devices 
• Finesse Bolus Insulin Delivery System cleared for 
commercialization in United States (US), Europe (EU), 
and Canada 
• FlexPen® (aspart) 
• SoloStar®  Pen (glargine)  
Study Purpose 
In order to enable the Healthcare Provider (HCP) to more 
easily advance patients with T2DM sub-optimally controlled 
on basal insulin therapy to basal and bolus therapy, a novel 
bolus insulin patch (“Finesse”) was developed by the 
Sponsor. The proposed study aims to determine whether 
initiating and managing bolus therapy with Finesse will 
result in non-inferior or improved glycemic control in patients 
with T2DM compared with a pen. 
Study Objectives 
Primary Objective: 
To compare the change in A1C, with bolus insulin dosing 
with Finesse versus pen, from baseline to the completion of 
24 weeks of basal and bolus insulin therapy. 
Secondary Objectives: 
• To compare the change in other parameters of glycemic 
control with bolus insulin dosing with Finesse versus 
pen, from baseline to the completion of 24 weeks and 44 
weeks of basal and bolus insulin therapy. 
• To demonstrate that patient reported outcomes (PRO) 
improve with Finesse versus pen following the 
completion of 24 weeks and 44 weeks of basal and 
bolus insulin therapy. 
• To demonstrate that HCPs prefer Finesse to pen for 
initiation of bolus insulin therapy following the completion 
of 24 weeks of basal and bolus insulin therapy by the 
last patient at their investigative site. 

• To demonstrate the durability of effect of using Finesse 
and pen on maintenance of A1C from week 24 to week 
44 of basal and bolus insulin therapy. 
• To demonstrate that patients prefer Finesse to pen for 
bolus insulin therapy following a 4-week crossover from 
week 44 to week 48. 
Study Design  
A randomized, open-label, 2-arm parallel study comparing 
glycemic control, patient satisfaction, and quality of life 
(QOL) of using Finesse versus pen to initiate and manage 
bolus insulin dosing in 312 patients, male and female, ages 
22 to 75 years of age with T2DM not achieving glycemic 
targets on basal insulin with/without AHA. After a 4-week 
screening/baseline period, patients will be randomized 1:1 
(balanced by study center) to either the Finesse arm or the 
pen arm to initiate bolus insulin using a simple bolus dosing 
algorithm and followed for a 44-week intervention period. 
After the final endpoint evaluation at week 44, patients will 
crossover to the alternate bolus insulin delivery device for 4 
weeks and complete a patient preference survey at week 
48. 
The study will be conducted in the following periods: 
Screening Visit 1 (Week -4 to -3); Baseline Visit 2A (Week      
-2); Randomization Visit 3 (Week 0) to include insulin 
dosage optimization;i,1 Phone Calls Insulin Titration (Weeks 
1, 2, 3, 6, 8); Follow-up Visits 4 (Week 4), 5 (Week 12), 6C 
(Week 24), 7 (Week 36), 8 (Week 44), and 9 (Week 48).   
Visits 2B (Week -1), 6A (Week 22), and 6B (Week 23): Only 
the subset of patients performing continuous glucose 
monitoring (CGM) (50 patients per arm) will have additional 
visits for performing blinded CGM assessments.  
Study Sites 
A multicenter study (approximately 50 sites). Sites and 
patients will be approximately divided between the US and 
EU.  
Patient Population 
A total of approximately 312 enrolled adults, male and 
female, aged 22-75 years, body mass index of ≤ 40 kg/m2, 
with T2DM not achieving glycemic targets (A1C 7.5-11.0%) 
                                                          
i Educational materials specifically designed for this study based on the International Diabetes Center 
simple algorithm for adjustment of insulin in Type 2 diabetes. Patients will record SMBG before meals and 
bedtime, and insulin doses. 
 

using basal insulin (≥ 0.3 U/kg/day) with/without AHA based 
on the participant’s medical needs.  
Duration of Patient 
Participation 
Total duration of participation by each patient is expected to 
be approximately 52 weeks.  
Dosage and 
Administration 
At randomization, total daily dose (TDD) of insulin will be 
divided as 50:50, basal: bolus (Note: For those subjects with 
a screening A1C of <9%, the TDD is to be reduced by 10% 
prior to splitting the dose 50:50, basal: bolus, in order to 
avoid potential for hypoglycemia at institution of new 
regimen). Basal insulin therapy for each group will be 
titrated using a simple algorithm by chart to adjust by 2U 
increments to achieve pre-morning meal fasting plasma 
glucose (FPG) target of 71-130 mg/dl (4.0-7.2 mmol/l). 
Bolus insulin dosing will start with fixed pre-meal doses 
(divided equally between morning meal, midday meal, and 
evening meal).2 Prandial insulin therapy for each group will 
be titrated using a simple algorithm by chart to adjust by 2U 
increments based on pre-midday meal and pre-evening 
meal self-monitoring blood glucose (SMBG) target of 71-130 
mg/dl (4.0-7.2 mmol/l) and bedtime SMBG target of 71-130 
mg/dl (4.0-7.2 mmol/l): pre-morning meal dose will be 
titrated based on pre-midday meal SMBG; pre-midday meal 
dose will be titrated based on pre-evening meal SMBG; pre-
evening meal dose will be titrated based on bedtime SMBG. 
For basal insulin, all patients will use Lantus® (Glargine) by 
a pen (SoloStar®) before evening meal or at bedtime. For 
bolus insulin, patients will use Finesse containing rapid-
acting NovoLog®/NovoRapid® (Aspart) or the FlexPen®.  
Patients will discontinue the following AHA: Sulfonylureas, 
Meglitinides, GLP-1 agonists, bromocriptine, and DPP-4 
inhibitors that have not been studied in combination with 
insulin, namely, saxagliptin and linagliptin. Patients on the 
following AHAs will continue them in their current doses: 
Biguanides, Alpha-glucosidase inhibitors, SGLT2 inhibitors, 
Thiazolidinediones, and DPP-4 inhibitors that have been 
studied and approved for use in combination with insulin, 
namely, sitagliptin, alogliptin, and vildagliptin.  
Endpoint Evaluation at Week 24 
Primary Endpoint  
Change in A1C from baseline to week 24, comparing 
Finesse versus Pen. 
Secondary Endpoints  
• Proportion of patients with A1C ≤ 7.0% at week 24;  

• Change in percent of glucose values of CGM 
measurements (in a subset of patients) within targeted 
range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) from a 
one or two week period of week -2 to week 0 (baseline) 
to a one or two week period of week 22 to week 24; 
• Change in 3-day average 7-point SMBG from baseline to 
week 24;  
• Change in 3-day coefficient of variation (CV) of 7-point 
SMBG from baseline to week 24; 
Tertiary Endpoints  
• Change in A1C from baseline to week 12; 
• Change in average glucose values of CGM 
measurements (in a subset of patients) from a one or 
two week period of week -2 to week 0 (baseline) to a 
one or two week period of week 22 to week 24.  
• Change in percent of glucose values of CGM 
measurements (in a subset of patients) ≤ 70 mg/dl (≤3.9 
mmol/l) and percent of values >180 mg/dl (>10.0 mmol/l) 
from a one or two week period of week -2 to week 0 
(baseline) to a one or two week period of week 22 to 
week 24;  
• Change in FPG from baseline to week 24; 
• Change in 3-day insulin doses (total daily dose, basal 
dose, bolus dose) from baseline to week 24. 
Patient Reported 
Outcomes  
• Change in treatment satisfaction for insulin delivery from 
baseline to week 24;  
• Change in patient quality of life from baseline to week 
24; 
• Patient experience survey at week 24; 
• Patient insulin usage survey at week 12 and 24. 
Healthcare Provider 
Reported Outcomes 
• HCP experience survey at week 24. 
Endpoint Evaluation at Week 44 
Secondary Endpoints  
• Change in A1C from baseline to week 44; 
• Proportion of patients with A1C ≤ 7.0% at week 44;  
• Change in 3-day average 7-point SMBG from baseline to 
week 44;  
• Change in A1C from week 24 to week 44. 
Tertiary Endpoints 
• Change in A1C from baseline to week 36;  
• Change in 3-day CV of 7-point SMBG from baseline to 
week 44.  
• Change in FPG from baseline to week 44; 

• Change in 3-day insulin doses (total daily dose, basal 
dose, bolus dose) from baseline to week 44. 
Patient Reported 
Outcomes  
• Patient experience survey at week 44; 
• Patient insulin usage survey at week 36 and 44. 
Endpoint Evaluation at Week 48 
Patient Reported 
Outcomes  
• Patient preference survey at week 48. 
Safety Observations 
• Incidence and rate of severe hypoglycemiaii,3  
• Incidence and rate of non-severe hypoglycemia (≤70 
mg/dl) (≤3.9 mmol/l) (both symptomatic and 
asymptomatic);  
• Incidence of all adverse events;  
• Incidence of serious adverse events; 
• Incidence of adverse device effects; 
• Incidence of serious adverse device effects;  
• Discontinuation rate due to adverse events. 
• Incidence of clinically important changes in clinical 
laboratory tests, vital signs (pulse, blood pressure), 
physical examination, and body weight. 
Data Analysis  
Analysis Sets 
The intent-to-treat (ITT) analysis set includes all patients 
who initiated bolus insulin therapy. The modified intent-to-
treat (mITT) analysis set includes all the ITT patients who 
had a baseline and at least one post-baseline A1C 
measurement.  The per protocol (PP) analysis set consists 
of all mITT patients who complete the 24-week efficacy 
phase, and have no major protocol deviations that may 
affect the interpretation of the primary efficacy endpoint. 
Efficacy measurements will be summarized for both mITT 
and PP analysis sets; the primary efficacy analyses will be 
based on the mITT analysis set. The ITT set will be used for 
all safety analyses. 
Sample Size Determination 
                                                          
ii Severe hypoglycemia is defined as an event requiring the assistance of another person to actively 
administer carbohydrate (including IV dextrose), glucagon, or other resuscitative actions. These episodes 
may be associated with sufficient neuroglycopenia to induce seizure or coma. Neurological recovery 
attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event 
was induced by a low plasma glucose concentration. 

The sample size determination is based on the primary 
endpoint, A1C change from baseline to Week 24. Assuming 
that the true mean difference in A1C change (Finesse vs 
Pen) is -0.1% with a SD 1.2%, a study population of 250 
completers (125 per arm) is required to achieve a power of 
90% for non-inferiority with a margin of 0.4%, i.e., the upper 
bound 2-sided 95% confidence interval of the difference in 
mean A1C change (Finesse vs Pen) is less than 0.4%. 
Assuming a discontinuation rate of 20% (for the 24 week 
primary endpoint analysis), the number of patients to be 
enrolled = 250/(1-0.20) = 312 patients (156 per arm). 
Efficacy Analysis Plan 
Differences between arms (Finesse arm versus pen arm) at 
week 24 will be analyzed using analysis of covariance 
(ANCOVA) model with the baseline A1C value as the 
covariate; the 2-sided 95% confidence interval of the 
difference will be computed using the model. The non-
inferiority of Finesse to pen will be concluded if the upper 
bound of the 95% 2-sided confidence interval for change in 
A1C is less than the inferiority margin of 0.4%. This test is 
the same as a 1-sided test with an alpha of 0.025. 
Superiority of Finesse will be tested if non-inferiority is 
shown. 
Each of the secondary and tertiary endpoints at week 24 
and week 44 will be tested for superiority of the Finesse arm 
to the pen arm, but the tests will be interpreted inferentially 
only if non-inferiority is demonstrated with respect to the 
primary endpoint.  Otherwise, the p-values and 95% 
confidence intervals for the secondary and tertiary 
endpoints will be considered to be nominal.  The continuous 
endpoints will be analyzed using the same ANCOVA model 
described for the primary endpoint. The categorical 
endpoints will be analyzed using a Cochran-Mantel-
Haenszel test. The Type 1 error rate will be at 0.05. 
To evaluate durability of effect of using Finesse versus pen, 
change in A1C from 24 week to 44 week will be analyzed by 
treatment groups using t-test for each treatment arm. 

Other general considerations for the statistical analysis will 
include descriptive statistics (sample size, mean, SD, 
median, minimum, and maximum) for continuous variables 
and 95% CI of the mean, and, where appropriate, the 
percentage values for categorical variables, and tests of 
significance between treatment arms including p-value and 
95% CI.    
Additional Analyses 
Analyses will also be performed to examine the 
relationships between variables known to be associated. In 
particular, the relationship between A1C and severe 
hypoglycemiaiii, the relationship between A1C and weight 
change, and the relationship between A1C and adherence 
measures will be described in each group. These analyses 
will be descriptive, primarily using categorical cross-
classifications to examine whether any shifts in 
hypoglycemia, weight change, or adherence measures are 
consistent with expected changes due to improved glycemic 
control.  
 
                                                          
iii Severe hypoglycemia is defined as an event requiring the assistance of another person to actively 
administer carbohydrate (including IV dextrose), glucagon, or other resuscitative actions. These episodes 
may be associated with sufficient neuroglycopenia to induce seizure or coma. Neurological recovery 
attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event 
was induced by a low plasma glucose concentration. 

 
1 Handelsman Y, Mechanick JI, Blonde L, et al. American association of clinical endocrinologists medical 
guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan: executive 
summary. Endocrine Practice 17:287-302, 2011. 
 
2 Liebl A, Prager R, Binz K, Kaiser M, Bergenstal R, Gallwitz B; PREFER Study Group. Comparison of 
insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized 
controlled trial. Diabetes Obes Metab 11:45-52, 2009. 
 
3 American Diabetes Association Work Group on Hypoglycemia. Defining and reporting hypoglycemia in 
diabetes. Diabetes Care 28:1245-1249, 2005.