| Outcome Measures: |
Primary: Change in Mean Glucagon Concentration During Induced Hypoglycemia From Target Plasma Glucose (PG) Concentration of 100 Milligrams Per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL, A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using restricted maximum likelihood (REML) method was used. PG of plateau 100 mg/dL was considered as baseline timepoint., Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. | Secondary: Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL, A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used., Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.|Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL, A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used., Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.|Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL), A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used., Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins).|Hypoglycemia Symptoms Score From Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL), Hypoglycemia symptoms score was measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) which is a 13-item questionnaire for hypoglycemic symptoms: 10 neuroglycopenic symptoms (6 cognitive dysfunctions: inability to concentrate, blurred vision, anxiety, confusion, difficulty speaking, and double vision; 4 neuroglycopenia: drowsiness, tiredness, hunger, and weakness), and 3 autonomic symptoms (sweating, trembling, and warmness) and participants were asked to rate the intensity of their hypoglycemic symptoms on a 7-point Likert scale (1 = No symptom to 7 = Severe). The total score is the sum of scores from the 13 questions and ranged from 13 to 91. This score was scaled back to the range of 1 to 7 by taking average of the sum of scores (i.e., sum of the scores divided by number of questions), where lower score indicates fewer symptoms., Week 12.|Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL, A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used., Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.|Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL, A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used., Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
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