Evaluation of Virtual Versus Traditional Study Conducted in a Group Pilot Study in Adult Patients With Type 1 Diabetes Mellitus (eStudy)

Study Overview
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Brief Summary
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Primary Objective: To evaluate the effect of virtual approach via novel technologies versus traditional study conduct on glycemic control in terms of glycated hemoglobin (HbA1c). Secondary Objective: To evaluate the appropriate utilization of virtual approach via novel technologies during the study and to assess the effect of the virtual versus traditional study conduct on multiple outcomes in terms of study methodology and diabetes management.

Detailed Description
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The study had a maximum study duration of 29 weeks, which consisted of a 3-week screening period (including a possible 1-week delay in first investigational medicinal product [IMP] administration after randomization in virtual group due to shipment of IMP and the virtual devices), a 24-week treatment period, and 1-week post-treatment safety follow-up period.

Official Title
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Evaluation of Virtual Versus Traditional Study Conduct in a 6-month, Multicenter, Randomized, Open-label, Two-parallel Group Pilot Study in Adult Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine, 300 units per milliliter (U/mL)
* Drug: Background therapy: Rapid Acting meal time insulin analogs (Humalog, Novolog or Apidra)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with Type 1 diabetes mellitus (T1DM) diagnosed at least one year before the screening visit. Participants who were treated with multi-dose insulin using insulin glargine 100 U/mL (eg, Lantus or Basaglar) as basal insulin and rapid acting insulin analogues as bolus insulin. Participants with access to or experience with mobile technology (eg, tablet or smart phone). eSign the consent on the study web portal. Exclusion criteria: Age less than (<) 18 years at screening (Visit 1 - Step 1). Type 2 diabetes mellitus. HbA1c <5.4 percent (%) or greater than or equal to (>=) 9.0% measured by the central lab at Visit 1. Participants who received <6 months treatment with any basal plus (+) meal-time insulin. Use of any basal insulins other than insulin glargine 100 U/mL (eg, Lantus or Basaglar) within 3 months before screening. Use of an insulin pump within 6 months before screening. Use of meal-time insulin other than rapid-acting insulin analogs (Humalog, Novolog, or Apidra), eg, human regular insulin, within 30 days before screening. Hemoglobinopathy resulting in undetectable HbA1c by the central laboratory, or hemolytic anemia requiring transfusion of blood or plasma products within 3 months before screening. Participants experienced with any severe hypoglycemic episode resulting in seizure, unconsciousness, or coma, and/or leading to hospitalization during the past 6 months before screening. Participants with insufficient smart phone skills or unwilling to properly use the virtual tools deemed by the investigator based on the observation and experiences over the digital screening procedure-Mental disorders or any neurologic disorder that would affect participant's ability to meet the study requirements, or participants deemed unlikely to safely manage insulin dosage by the investigator. Known hypersensitivity/intolerance to insulin glargine, rapid-acting insulin analogs or any of their excipients. Pregnant or breast-feeding women, or women who intend to become pregnant during the study period. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Virtual<br>Participants included in this virtual trial approach group did not visit the study sites during the study course. All study assessments, including vital signs, weight, laboratory variables, etc., were completed via the Bluetooth devices that instantly transfer the digital data. | Drug: Insulin glargine, 300 units per milliliter (U/mL)<br>* Self-administered subcutaneous injection using prefilled pen once daily for 24 weeks. Dose titration to achieve fasting self-monitoring of plasma glucose (SMPG) level between 80 and 130 milligram per deciliter (mg/dL).<br>* Other names: Toujeo ®;Drug: Background therapy: Rapid Acting meal time insulin analogs (Humalog, Novolog or Apidra)<br>* Subcutaneous injection.<br>|
| Active Comparator: Traditional<br>Participants included in this traditional trial approach group visited the study site, followed the study visit schedules for all study assessments that was performed either in-person or phone visits. | Drug: Insulin glargine, 300 units per milliliter (U/mL)<br>* Self-administered subcutaneous injection using prefilled pen once daily for 24 weeks. Dose titration to achieve fasting self-monitoring of plasma glucose (SMPG) level between 80 and 130 milligram per deciliter (mg/dL).<br>* Other names: Toujeo ®;Drug: Background therapy: Rapid Acting meal time insulin analogs (Humalog, Novolog or Apidra)<br>* Subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycated Hemoglobin A1c (HbA1c) to Week 24 | Change in HbA1c was calculated by subtracting baseline value from Week 24 value. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycated Hemoglobin A1c to Week 16 | Change in HbA1c was calculated by subtracting baseline value from Week 16 value. | Baseline, Week 16 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) to Week 16 and Week 24 | Change in FPG was calculated by subtracting baseline value from Week 16 value (for change at Week 16) and Week 24 (for change at Week 24) value. | Baseline, Week 16, Week 24 | 
| Participant Satisfaction With Trial Experience: Was It Worth It (WIWI) Questionnaire Response at Week 24 | Participant satisfaction with trial experience was measured using the WIWI questionnaire. The WIWI had 5 questions, 3 questions with level categorical response (Yes, No, and Unsure) scale, 1 question with 3 possible answers as: Better than I expected/The same as I expected/Worse than I expected, and 1 question with 3 possible answers: It improved/Stayed the same/Become worse. | At Week 24 | 
| Change From Baseline in Work Productivity and Impairment-Study Participation (WPAI-SP) Scores to Week 24 | Effect of trial on a participants' ability to work and perform regular activities were measured using WPAI-SP. WPAI-SP had 6 items scored separately, where higher score indicated greater impairment and less productivity. | Baseline, Week 24 | 
| Change From Baseline in Overall Study Experience-Participation (OSEP) Part-1 Questionnaire Score to Week 24 | Participant burden with trial participation was measured using the OSEP Questionnaire, administered electronically. OSEP Part-1 contained 4 items to examine perceptions of study participation. Each item was measured on an 11 point scale ranged from 0 (completely disagree) to 10 (completely agree), where higher score indicated higher perception of diabetes control. | Baseline, Week 24 | 
| Change From Baseline in Overall Study Experience-Participation Part-2 Questionnaire Score to Week 24 | Participant burden with trial participation was measured using the OSEP Questionnaire, administered electronically. OSEP Part-2 contained 9 items to examine perceptions of study participation. Each item was measured on an 11 point scale ranged from 0 (completely disagree) to 10 (completely agree), where higher score indicated higher burden with trial participation. | Baseline, Week 24 | 
| Resource Use Questionnaire (RUQ) Scores | Healthcare resource use was measured using the RUQ which asked participants to report the resources used (time and expenses) during the previous 4 weeks in terms of visits to healthcare professionals. | During 24 weeks treatment period | 
| Change From Baseline in Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) to Week 24 | The DTSQs was a validated questionnaire to assess participant's satisfaction with their diabetes treatment. It consisted of 8 items that were answered on a Likert scale from 0 (no satisfaction) to 6 (high satisfaction with treatment). Total treatment satisfaction score was the sum of items 1, 4-8 scores and ranged from 0 (no satisfaction) to 36 (high satisfaction with treatment). | Baseline, Week 24 | 
| Change From Baseline in Diabetes Treatment Satisfaction Questionnaire Change (DTSQc) Score to Week 24 | DTSQc measured the relative change in treatment satisfaction from previous therapy. It consists of 8 items that were answered on a 6 point scale ranges from 3 (much less satisfied) to -3 (much more satisfied). Total treatment satisfaction score was the sum of items 1, 4-8 scores and ranged from -18 (much less satisfied) to +18 (much more satisfied), higher score indicated more satisfaction. | Baseline, Week 24 | 
| Hypoglycemia Fear Survey-II (HFS-II) Scores | Fear of hypoglycemia was measured with HFS-II at Week 24. The HFS-II comprises 33 items: 15 items explore behaviors that participants were engaged in to avoid low blood sugar and its negative consequences and 18 items related to concern/worry that participants had about their hypoglycemia. Responses to each item were made on a 5-point Likert scale ranges from 0 equal (=) Never to 4 = Always. Total HFS mean score was determined by computing the mean of all 33 items and the score ranged from 0 to 4, where higher score indicated more fear/worry. | At Week 24 | 
| Diabetes Distress Scale (DDS) Scores | Diabetes-related distress was measured using DDS. The DDS contained 17 items related to potential problem areas that people with diabetes may experience. Participants were asked to consider the degree to which each of the items might have distressed or bothered them during the past month, and respond for each item on a 7 point scale ranges from 1 (not a problem) to 6 (a very serious problem), higher score indicated more diabetes related distress. | Week 0, Week 24 | 
| Change From Baseline in 7-Point Self-Monitoring of Plasma Glucose (SMPG) Profiles at Week 16 and Week 24 Per Time Point | 7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, Week 16, and Week 24): before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, and bedtime. For each time point, the value at each visit was calculated as the average of values obtained for the same time point across profiles performed in the week before the visit. | Baseline, Week 16, Week 24 | 
| Average Daily Insulin Doses | Average daily insulin doses included basal insulin doses, mealtime insulin doses, and total insulin doses. | During 24 weeks treatment period | 
| Overall Study Experience-Sites (OSES) Questionnaire Part-1: Hours Spent by Investigator | An OSES questionnaire was completed by Site Investigator and had 2 parts. The OSES Part-1 contained quantitative 1 item (question) to examine resource requirements which was: Approximately how much time did you spend with this participant (in person or via phone) during this scheduled visit/communication? (hours) | During 24 weeks treatment period | 
| Overall Study Experience-Sites Questionnaire Part-2 Scores for Site-Perceived Participant Relationship and Satisfaction at Week 24 | An OSES questionnaire was completed by site investigator and had two parts. OSES Part-2 contains 2 items to examine investigator-participant relationship and satisfaction with care. Both items were assessed on a scale of 0 [completely disagree] to 10 [completely agree]), where highest score indicated a good relationship and satisfaction with care. | At Week 24 | 
| Number of Participants With At Least One Hypoglycemic Events (Any, Severe Documented Symptomatic, Probable Symptomatic, Asymptomatic, Pseudo-hypoglycemia: Any Time of the Day) During 24 Week Treatment Period | Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (70 mg/dL) or <3.0 mmol/L (54 mg/dL). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration <=3.9 mmol/L (70 mg/dL) or <3.0 mmol/L (54 mg/dL). Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration. Pseudo-hypoglycemia: an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration >3.9 mmol/L (70 mg/dL). | During 24 weeks treatment period |