Type1 Diabetes
Conditions
Keywords
new onset, verapamil, hybrid closed loop, hcl, beta cell, diabetes, children, T1D, c-peptide, pediatric
Brief summary
Randomized trial of youth aged 7-\<18 years with newly diagnosed stage 3 type 1 diabetes (T1D) to assess the effect of both (1) near-normalization of glucose concentrations achieved through use of a hybrid closed loop (HCL) system and (2) verapamil on preservation of β-cell function 12 months after diagnosis. Participants with body weight ≥30 kg (Cohort A) will be randomly assigned in a factorial design to (1) HCL plus intensive diabetes management or usual care with no HCL and (2) verapamil or placebo. Participants with body weight \<30 kg (Cohort B) will be randomly assigned 2:1 in a parallel group design to HCL plus intensive diabetes management or to usual care with no HCL.
Detailed description
After informed consent is obtained, potential participants will be assessed for eligibility, including eliciting medical history, physical examination, and laboratory testing (including HbA1c, auto-antibody measurement \[unless positive auto-antibody results already available\], and pregnancy test for females with childbearing potential). Participants who already have positive auto-antibodies can be randomized immediately. All other participants will be scheduled for a randomization visit after the auto-antibody results are available; positive auto-antibodies are required for randomization. Eligible participants with body weight ≥30 kg (Cohort A) will be randomly assigned to one of 4 groups: HCL and placebo, HCL and verapamil, non-HCL and placebo or non-HCL and verapamil. Eligible individuals with body weight \<30 kg (Cohort B) will be randomly assigned 2:1 to either HCL or non-HCL. Randomization schedules will be separate for Cohort A and Cohort B and will be stratified by site. Participants assigned to HCL will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations. Participants assigned to non-HCL will receive a Dexcom G6 continuous glucose monitor (CGM) and diabetes management will follow usual care by their personal diabetes health care provider. Participants will be followed for 12 months from diagnosis, completing a 6 week visit timed from randomization and 13, 26, 39, and 52 week visits timed from diagnosis. Participants will have a MMTT performed, HbA1c measured, and blood drawn for mechanistic studies at Randomization, 13, 26, 39 and 52 weeks. At all follow-up visits, a physical exam will be performed, pregnancy testing performed (if indicated), insulin dose (units/kg/day) recorded, and device data downloaded. Safety assessments will be made throughout the study by querying about episodes of severe hypoglycemia and DKA, and overall health. Participants already enrolled in the study and using the Medtronic 670G 4.0 AHCL may transition to the Medtronic 780G if desired. Contacts will be performed to review CareLink data and check for adverse events and device deficiencies on days 1, 3 and 5 after transition from 670G 4.0 AHCL to 780G. Prior to the 780G system becoming commercially available, study participants using the Medtronic system at 52 weeks will have the opportunity to continue using the 780G system at home until the system is commercially available OR until the CLVer trial is complete (last participant's 52-week visit), whichever comes first. Additional Procedures for Cohort A: Drug will be double blinded. Drug dose will be weight-dependent and will be escalated at 2-4 week intervals, up to a weight-dependent maximum if tolerated. Cohort A will have additional safety visits 1 week after initiation of study drug and after each study drug dose increase, to test blood pressure and pulse. Local lab measurement of aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine will occur, and an EKG will be performed at Screening, 6, 26, and 52 weeks. Over the course of the trial, study drug dose may be decreased or discontinued if side effects occur.
Interventions
DEVICEHCL
Hybrid Closed Loop therapy
DRUGverapamil 120mg tablet
verapamil tablet
DEVICEnon-HCL
Usual diabetes care
DRUGplacebo
placebo pill manufactured to mimic verapamil 120mg tablet
Sponsors
Juvenile Diabetes Research Foundation
University of Minnesota
DexCom, Inc.
Medtronic
Tandem Diabetes Care, Inc.
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant Inclusion Criteria: 1. New-onset stage 3 T1D within 21 days of diagnosis (timed from start of insulin therapy), with ability to be randomized within 31 days of diagnosis (time from diagnosis to screening can be longer provided all screening testing can be completed within 31 days of diagnosis) 2. At least one positive type 1 diabetes auto-antibody 3. Age 7 - \<18 years at the time of enrollment 4. Willing to have a parent or legal guardian provide informed consent and child assent 5. In a female participant with childbearing potential, not currently pregnant and willing to avoid pregnancy and breastfeeding and undergo pregnancy testing throughout the study 6. English speaking/reading 7. Able to swallow pills (tested with an inert imitation tablet in clinic prior to randomization) 8. Willing to not use any non-insulin glucose-lowering agents 9. Willing to use an insulin approved for the pump (if assigned to HCL) 10. Willing to avoid medications containing acetaminophen, and no contraindications for ibuprofen use (in case assigned to Medtronic HCL system) * Participant
Exclusion criteria
1. Ongoing use of medications known to influence glucose tolerance such as systemic steroids 2. Other systemic disease which in the opinion of the investigator precludes participation (including psychiatric illness) 3. Unwilling to abstain from use of HCL therapy for 12 months a. Personal pump and CGM use, including systems with a suspend-before-low function, will be allowed for participants randomized to non-HCL groups 4. Silent diabetes-i.e., Stage 3 diabetes that is identified by routine oral glucose tolerance testing (OGTT) or in the course of surveillance studies but is not accompanied by fasting hyperglycemia or classic symptoms of diabetes 5. Participation in another research study that involves diabetes care * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide Area Under the Curve (AUC) | 52 weeks | The primary outcome is the C-peptide in response to a 2-hour MMTT at 52 weeks. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of CGM Time in Range 70-140 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | Percentage of CGM sensor glucose values from 70 to 140 mg/dL between treatment groups |
| Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks | 52 Weeks | Percentage of patients with \>=70% sensor glucose values from 70 to 180 mg/dL between treatment groups |
| Percentage of CGM Time >140 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | CGM sensor glucose values \>140 mg/dL between treatment groups |
| C-peptide AUC | 13, 26 and 39 weeks | C-peptide AUC between treatment groups. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min. |
| Peak C-peptide | 13, 26, 39 weeks and 52 weeks | Maximum of all C-peptide values during the MMTT |
| Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 13, 26, 39 weeks and 52 weeks | Percentage where maximum of all C-peptide values during the MMTT \>= 0.2 pmol/ml |
| CGM Mean Glucose | 6, 13, 26, 39 weeks and 52 weeks | Mean glucose between treatment groups |
| Percentage of CGM Time >180 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | CGM sensor glucose values \>180 mg/dL between treatment groups |
| Percentage of CGM Time >250 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | Percentage of CGM sensor glucose values \>250 mg/dL between treatment groups |
| Percentage of CGM Time in Range (70-180 mg/dL) | 6, 13, 26, 39 weeks and 52 weeks | CGM sensor glucose values from 70 to 180 mg/dL between treatment groups |
| Percentage of CGM Time <70 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | Percentage of CGM sensor glucose values \<70 mg/dL between treatment groups |
| CGM Coefficient of Variation | 6, 13, 26, 39 weeks and 52 weeks | Coefficient of variation between treatment groups. Calculated as the standard deviation of CGM glucose values divided by the mean of CGM glucose values. |
| HbA1c | 13, 26, 39 weeks and 52 weeks | HbA1c between treatment groups |
| Number of Participants With HbA1c <7.0% | 13, 26, 39 weeks and 52 weeks | Percentage of participants with HbA1c \< 7.0% between treatment groups |
| Number of Participants With HbA1c <6.5% | 13, 26, 39 weeks and 52 weeks | Percentage of participants with HbA1c \< 6.5% between treatment groups |
| Total Daily Insulin Per kg | 6, 13, 26, 39 weeks and 52 weeks | Total daily insulin per kg between treatment groups |
| Basal:Bolus Ratio | 6, 13, 26, 39 weeks and 52 weeks | Ratio of basal:bolus insulin between treatment groups |
| Severe Hypoglycemia | 52 weeks | Frequency of episodes of severe hypoglycemia between treatment groups |
| DKA | 52 weeks | Frequency of episodes of DKA between treatment groups |
| Percentage of CGM Time <54 mg/dL | 6, 13, 26, 39 weeks and 52 weeks | Percentage of CGM sensor glucose values \<54 mg/dL between treatment groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HCL and Verapamil Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations.
Verapamil will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.
Whether drug is active or placebo is blinded to both participant and site. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\] HCL: Hybrid Closed Loop therapy verapamil 120mg tablet: verapamil tablet | 22 |
| HCL and Placebo Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations.
Placebo will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.
Whether drug is active or placebo is blinded to both participant and site. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\] HCL: Hybrid Closed Loop therapy placebo: placebo pill manufactured to mimic verapamil 120mg tablet | 20 |
| Non-HCL and Verapamil Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider.
Verapamil will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.
Whether drug is active or placebo is blinded to both participant and site. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\] verapamil 120mg tablet: verapamil tablet non-HCL: Usual diabetes care | 25 |
| Non-HCL and Placebo Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider.
Placebo will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.
Whether drug is active or placebo is blinded to both participant and site. \[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\] non-HCL: Usual diabetes care placebo: placebo pill manufactured to mimic verapamil 120mg tablet | 21 |
| HCL Only Participants weighing \<30 kg at study enrollment were randomly assigned 2:1 in a parallel group design to HCL plus intensive diabetes care or usual care with no HCL.
Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations.
HCL: Hybrid Closed Loop Therapy | 19 |
| Non-HCL Only Participants weighing \<30 kg at study enrollment were randomly assigned 2:1 in a parallel group design to HCL plus intensive diabetes care or usual care with no HCL.
Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider.
non-HCL: Usual diabetes care | 6 |
| Total | 113 |
Baseline characteristics
| Characteristic | Non-HCL Only | Non-HCL and Verapamil | Total | HCL and Verapamil | HCL Only | Non-HCL and Placebo | HCL and Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 9 years STANDARD_DEVIATION 1 | 13 years STANDARD_DEVIATION 3 | 12 years STANDARD_DEVIATION 3 | 13 years STANDARD_DEVIATION 3 | 8 years STANDARD_DEVIATION 1 | 13 years STANDARD_DEVIATION 2 | 12 years STANDARD_DEVIATION 2 |
| Annual Household Income >=$100,000 | 3 Participants | 15 Participants | 62 Participants | 12 Participants | 12 Participants | 8 Participants | 12 Participants |
| Annual Household Income <$50,000 | 0 Participants | 5 Participants | 17 Participants | 5 Participants | 2 Participants | 2 Participants | 3 Participants |
| Annual Household Income $50,000-<$100,000 | 3 Participants | 4 Participants | 26 Participants | 5 Participants | 5 Participants | 6 Participants | 3 Participants |
| Annual Household Income Missing | 0 Participants | 1 Participants | 8 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants |
| BMI Percentile at Randomization | 32 Percentile | 58 Percentile | 56 Percentile | 78 Percentile | 43 Percentile | 65 Percentile | 53 Percentile |
| Diastolic Blood Pressure at Randomization (mmHg) | 63 mmHg STANDARD_DEVIATION 7 | 65 mmHg STANDARD_DEVIATION 8 | 63 mmHg STANDARD_DEVIATION 7 | 62 mmHg STANDARD_DEVIATION 7 | 62 mmHg STANDARD_DEVIATION 8 | 65 mmHg STANDARD_DEVIATION 8 | 62 mmHg STANDARD_DEVIATION 6 |
| DKA at Diagnosis Missing | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| DKA at Diagnosis No | 2 Participants | 15 Participants | 60 Participants | 13 Participants | 7 Participants | 10 Participants | 13 Participants |
| DKA at Diagnosis Yes | 4 Participants | 10 Participants | 51 Participants | 8 Participants | 11 Participants | 11 Participants | 7 Participants |
| Health Insurance Missing | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Health Insurance None | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Health Insurance Private | 3 Participants | 22 Participants | 92 Participants | 16 Participants | 14 Participants | 18 Participants | 19 Participants |
| Health Insurance Public | 2 Participants | 3 Participants | 18 Participants | 4 Participants | 5 Participants | 3 Participants | 1 Participants |
| Highest Parental Education Advanced Degree | 2 Participants | 8 Participants | 37 Participants | 6 Participants | 9 Participants | 5 Participants | 7 Participants |
| Highest Parental Education Bachelor's | 3 Participants | 11 Participants | 48 Participants | 10 Participants | 8 Participants | 10 Participants | 6 Participants |
| Highest Parental Education Less than Bachelor's | 1 Participants | 6 Participants | 28 Participants | 6 Participants | 2 Participants | 6 Participants | 7 Participants |
| Lab HbA1c at Randomization (%) | 9.4 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.5 | 10.6 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.7 | 10.6 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.7 | 10.1 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.6 | 10.6 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.2 | 10.1 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.4 | 10.3 Percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.1 |
| Race/Ethnicity, Customized Race/Ethnicity American Indian/Alaskan Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black/African American | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 0 Participants | 4 Participants | 15 Participants | 4 Participants | 1 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity More than One | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 6 Participants | 20 Participants | 86 Participants | 16 Participants | 15 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 49 Participants | 8 Participants | 10 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 13 Participants | 64 Participants | 14 Participants | 9 Participants | 14 Participants | 11 Participants |
| Systolic Blood Pressure at Randomization (mmHg) | 95 mmHg STANDARD_DEVIATION 9 | 111 mmHg STANDARD_DEVIATION 7 | 107 mmHg STANDARD_DEVIATION 10 | 108 mmHg STANDARD_DEVIATION 11 | 103 mmHg STANDARD_DEVIATION 8 | 108 mmHg STANDARD_DEVIATION 9 | 107 mmHg STANDARD_DEVIATION 9 |
| Tanner Staging Group 1 | 5 Participants | 3 Participants | 44 Participants | 6 Participants | 18 Participants | 4 Participants | 8 Participants |
| Tanner Staging Group 2-5 | 1 Participants | 22 Participants | 69 Participants | 16 Participants | 1 Participants | 17 Participants | 12 Participants |
| Time Since Diagnosis at Randomization (days) | 23 Days STANDARD_DEVIATION 5 | 24 Days STANDARD_DEVIATION 5 | 24 Days STANDARD_DEVIATION 5 | 24 Days STANDARD_DEVIATION 5 | 23 Days STANDARD_DEVIATION 5 | 25 Days STANDARD_DEVIATION 4 | 24 Days STANDARD_DEVIATION 5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 | 0 / 25 | 0 / 21 | 0 / 19 | 0 / 6 |
| other Total, other adverse events | 20 / 22 | 16 / 20 | 19 / 25 | 14 / 21 | 18 / 19 | 4 / 6 |
| serious Total, serious adverse events | 3 / 22 | 1 / 20 | 1 / 25 | 3 / 21 | 1 / 19 | 0 / 6 |
Outcome results
Primary
C-peptide Area Under the Curve (AUC)
The primary outcome is the C-peptide in response to a 2-hour MMTT at 52 weeks. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.
Time frame: 52 weeks
Population: 1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was not analyzed. All other participants with at least one available measurement of C-Peptide AUC were included in the analysis model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | C-peptide Area Under the Curve (AUC) | Randomization | 0.57 (pmol/ml)*minutes | Standard Deviation 0.22 |
| HCL and Intensive Management | C-peptide Area Under the Curve (AUC) | 52 Weeks | 0.45 (pmol/ml)*minutes | Standard Deviation 0.3 |
| Non-HCL and Standard Care | C-peptide Area Under the Curve (AUC) | 52 Weeks | 0.50 (pmol/ml)*minutes | Standard Deviation 0.31 |
| Non-HCL and Standard Care | C-peptide Area Under the Curve (AUC) | Randomization | 0.60 (pmol/ml)*minutes | Standard Deviation 0.18 |
| Verapamil | C-peptide Area Under the Curve (AUC) | Randomization | 0.66 (pmol/ml)*minutes | Standard Deviation 0.2 |
| Verapamil | C-peptide Area Under the Curve (AUC) | 52 Weeks | 0.65 (pmol/ml)*minutes | Standard Deviation 0.31 |
| Placebo | C-peptide Area Under the Curve (AUC) | Randomization | 0.60 (pmol/ml)*minutes | Standard Deviation 0.22 |
| Placebo | C-peptide Area Under the Curve (AUC) | 52 Weeks | 0.44 (pmol/ml)*minutes | Standard Deviation 0.3 |
p-value: 0.8995% CI: [-0.11, 0.1]Mixed Models Analysis
p-value: 0.0495% CI: [0.01, 0.27]Mixed Models Analysis
Secondary
Basal:Bolus Ratio
Ratio of basal:bolus insulin between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCL and Intensive Management | Basal:Bolus Ratio | 26 Weeks | 0.59 Daily Basal/Bolus Ratio |
| HCL and Intensive Management | Basal:Bolus Ratio | 39 Weeks | 0.67 Daily Basal/Bolus Ratio |
| HCL and Intensive Management | Basal:Bolus Ratio | 52 Weeks | 0.69 Daily Basal/Bolus Ratio |
| HCL and Intensive Management | Basal:Bolus Ratio | 6 Weeks | 0.61 Daily Basal/Bolus Ratio |
| HCL and Intensive Management | Basal:Bolus Ratio | Randomization | 0.96 Daily Basal/Bolus Ratio |
| HCL and Intensive Management | Basal:Bolus Ratio | 13 Weeks | 0.61 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | 39 Weeks | 0.72 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | 26 Weeks | 0.85 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | Randomization | 1.0 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | 6 Weeks | 1.1 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | 52 Weeks | 0.75 Daily Basal/Bolus Ratio |
| Non-HCL and Standard Care | Basal:Bolus Ratio | 13 Weeks | 1 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | 13 Weeks | 0.89 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | Randomization | 1.1 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | 6 Weeks | 0.89 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | 26 Weeks | 0.72 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | 39 Weeks | 0.75 Daily Basal/Bolus Ratio |
| Verapamil | Basal:Bolus Ratio | 52 Weeks | 0.82 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | 52 Weeks | 0.72 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | 39 Weeks | 0.72 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | Randomization | 1.1 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | 13 Weeks | 0.82 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | 26 Weeks | 0.75 Daily Basal/Bolus Ratio |
| Placebo | Basal:Bolus Ratio | 6 Weeks | 0.85 Daily Basal/Bolus Ratio |
Secondary
CGM Coefficient of Variation
Coefficient of variation between treatment groups. Calculated as the standard deviation of CGM glucose values divided by the mean of CGM glucose values.
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | CGM Coefficient of Variation | 39 Weeks | 34 Coefficient of Variation Percentage | Standard Deviation 6 |
| HCL and Intensive Management | CGM Coefficient of Variation | 13 Weeks | 31 Coefficient of Variation Percentage | Standard Deviation 6 |
| HCL and Intensive Management | CGM Coefficient of Variation | 52 Weeks | 34 Coefficient of Variation Percentage | Standard Deviation 6 |
| HCL and Intensive Management | CGM Coefficient of Variation | 26 Weeks | 32 Coefficient of Variation Percentage | Standard Deviation 5 |
| HCL and Intensive Management | CGM Coefficient of Variation | 6 Weeks | 31 Coefficient of Variation Percentage | Standard Deviation 5 |
| Non-HCL and Standard Care | CGM Coefficient of Variation | 26 Weeks | 32 Coefficient of Variation Percentage | Standard Deviation 6 |
| Non-HCL and Standard Care | CGM Coefficient of Variation | 39 Weeks | 33 Coefficient of Variation Percentage | Standard Deviation 6 |
| Non-HCL and Standard Care | CGM Coefficient of Variation | 52 Weeks | 33 Coefficient of Variation Percentage | Standard Deviation 5 |
| Non-HCL and Standard Care | CGM Coefficient of Variation | 13 Weeks | 30 Coefficient of Variation Percentage | Standard Deviation 7 |
| Non-HCL and Standard Care | CGM Coefficient of Variation | 6 Weeks | 30 Coefficient of Variation Percentage | Standard Deviation 6 |
| Verapamil | CGM Coefficient of Variation | 26 Weeks | 30 Coefficient of Variation Percentage | Standard Deviation 6 |
| Verapamil | CGM Coefficient of Variation | 6 Weeks | 28 Coefficient of Variation Percentage | Standard Deviation 5 |
| Verapamil | CGM Coefficient of Variation | 13 Weeks | 29 Coefficient of Variation Percentage | Standard Deviation 6 |
| Verapamil | CGM Coefficient of Variation | 39 Weeks | 31 Coefficient of Variation Percentage | Standard Deviation 6 |
| Verapamil | CGM Coefficient of Variation | 52 Weeks | 32 Coefficient of Variation Percentage | Standard Deviation 6 |
| Placebo | CGM Coefficient of Variation | 39 Weeks | 33 Coefficient of Variation Percentage | Standard Deviation 5 |
| Placebo | CGM Coefficient of Variation | 13 Weeks | 29 Coefficient of Variation Percentage | Standard Deviation 6 |
| Placebo | CGM Coefficient of Variation | 6 Weeks | 30 Coefficient of Variation Percentage | Standard Deviation 6 |
| Placebo | CGM Coefficient of Variation | 26 Weeks | 31 Coefficient of Variation Percentage | Standard Deviation 5 |
| Placebo | CGM Coefficient of Variation | 52 Weeks | 33 Coefficient of Variation Percentage | Standard Deviation 5 |
Secondary
CGM Mean Glucose
Mean glucose between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | CGM Mean Glucose | 13 Weeks | 132 mg/dL | Standard Deviation 15 |
| HCL and Intensive Management | CGM Mean Glucose | 6 Weeks | 129 mg/dL | Standard Deviation 12 |
| HCL and Intensive Management | CGM Mean Glucose | 52 Weeks | 145 mg/dL | Standard Deviation 19 |
| HCL and Intensive Management | CGM Mean Glucose | 26 Weeks | 135 mg/dL | Standard Deviation 17 |
| HCL and Intensive Management | CGM Mean Glucose | 39 Weeks | 140 mg/dL | Standard Deviation 19 |
| Non-HCL and Standard Care | CGM Mean Glucose | 26 Weeks | 152 mg/dL | Standard Deviation 35 |
| Non-HCL and Standard Care | CGM Mean Glucose | 39 Weeks | 161 mg/dL | Standard Deviation 36 |
| Non-HCL and Standard Care | CGM Mean Glucose | 52 Weeks | 167 mg/dL | Standard Deviation 42 |
| Non-HCL and Standard Care | CGM Mean Glucose | 13 Weeks | 140 mg/dL | Standard Deviation 26 |
| Non-HCL and Standard Care | CGM Mean Glucose | 6 Weeks | 139 mg/dL | Standard Deviation 29 |
| Verapamil | CGM Mean Glucose | 13 Weeks | 134 mg/dL | Standard Deviation 22 |
| Verapamil | CGM Mean Glucose | 6 Weeks | 131 mg/dL | Standard Deviation 23 |
| Verapamil | CGM Mean Glucose | 26 Weeks | 138 mg/dL | Standard Deviation 32 |
| Verapamil | CGM Mean Glucose | 39 Weeks | 141 mg/dL | Standard Deviation 23 |
| Verapamil | CGM Mean Glucose | 52 Weeks | 151 mg/dL | Standard Deviation 27 |
| Placebo | CGM Mean Glucose | 39 Weeks | 155 mg/dL | Standard Deviation 38 |
| Placebo | CGM Mean Glucose | 13 Weeks | 134 mg/dL | Standard Deviation 22 |
| Placebo | CGM Mean Glucose | 6 Weeks | 132 mg/dL | Standard Deviation 22 |
| Placebo | CGM Mean Glucose | 26 Weeks | 144 mg/dL | Standard Deviation 27 |
| Placebo | CGM Mean Glucose | 52 Weeks | 159 mg/dL | Standard Deviation 41 |
p-value: <0.00195% CI: [-37, -14]Mixed Models Analysis
p-value: 0.7495% CI: [-25, 16]Mixed Models Analysis
Secondary
C-peptide AUC
C-peptide AUC between treatment groups. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.
Time frame: 13, 26 and 39 weeks
Population: 1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was not analyzed. All other participants had at least one available measurement of C-peptide AUC and were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | C-peptide AUC | Randomization | 0.57 (pmol/ml)*minutes | Standard Deviation 0.22 |
| HCL and Intensive Management | C-peptide AUC | Week 13 | 0.63 (pmol/ml)*minutes | Standard Deviation 0.23 |
| HCL and Intensive Management | C-peptide AUC | Week 26 | 0.62 (pmol/ml)*minutes | Standard Deviation 0.28 |
| HCL and Intensive Management | C-peptide AUC | Week 39 | 0.51 (pmol/ml)*minutes | Standard Deviation 0.3 |
| Non-HCL and Standard Care | C-peptide AUC | Week 13 | 0.69 (pmol/ml)*minutes | Standard Deviation 0.25 |
| Non-HCL and Standard Care | C-peptide AUC | Week 26 | 0.63 (pmol/ml)*minutes | Standard Deviation 0.28 |
| Non-HCL and Standard Care | C-peptide AUC | Week 39 | 0.57 (pmol/ml)*minutes | Standard Deviation 0.3 |
| Non-HCL and Standard Care | C-peptide AUC | Randomization | 0.60 (pmol/ml)*minutes | Standard Deviation 0.18 |
| Verapamil | C-peptide AUC | Week 26 | 0.77 (pmol/ml)*minutes | Standard Deviation 0.3 |
| Verapamil | C-peptide AUC | Week 13 | 0.75 (pmol/ml)*minutes | Standard Deviation 0.26 |
| Verapamil | C-peptide AUC | Week 39 | 0.71 (pmol/ml)*minutes | Standard Deviation 0.31 |
| Verapamil | C-peptide AUC | Randomization | 0.66 (pmol/ml)*minutes | Standard Deviation 0.2 |
| Placebo | C-peptide AUC | Week 39 | 0.52 (pmol/ml)*minutes | Standard Deviation 0.28 |
| Placebo | C-peptide AUC | Week 13 | 0.69 (pmol/ml)*minutes | Standard Deviation 0.23 |
| Placebo | C-peptide AUC | Randomization | 0.60 (pmol/ml)*minutes | Standard Deviation 0.22 |
| Placebo | C-peptide AUC | Week 26 | 0.62 (pmol/ml)*minutes | Standard Deviation 0.25 |
p-value: 0.895% CI: [-0.1, 0.08]Mixed Models Analysis
p-value: 0.895% CI: [-0.08, 0.13]Mixed Models Analysis
p-value: 0.895% CI: [-0.13, 0.09]Mixed Models Analysis
p-value: 0.6995% CI: [-0.09, 0.13]Mixed Models Analysis
p-value: 0.0895% CI: [-0.02, 0.25]Mixed Models Analysis
p-value: 0.0895% CI: [-0.01, 0.28]Mixed Models Analysis
Secondary
DKA
Frequency of episodes of DKA between treatment groups
Time frame: 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCL and Intensive Management | DKA | 1 Number of DKA Events |
| Non-HCL and Standard Care | DKA | 1 Number of DKA Events |
| Verapamil | DKA | 0 Number of DKA Events |
| Placebo | DKA | 1 Number of DKA Events |
Secondary
HbA1c
HbA1c between treatment groups
Time frame: 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | HbA1c | 39 Weeks | 6.6 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.7 |
| HCL and Intensive Management | HbA1c | 13 Weeks | 6.4 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.5 |
| HCL and Intensive Management | HbA1c | 52 Weeks | 6.5 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.7 |
| HCL and Intensive Management | HbA1c | 26 Weeks | 6.4 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.6 |
| HCL and Intensive Management | HbA1c | Randomization | 10.3 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.3 |
| Non-HCL and Standard Care | HbA1c | 26 Weeks | 6.6 Percentage of Glycosylated Hemoglobin | Standard Deviation 1 |
| Non-HCL and Standard Care | HbA1c | 39 Weeks | 7.0 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.2 |
| Non-HCL and Standard Care | HbA1c | 52 Weeks | 7.1 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.3 |
| Non-HCL and Standard Care | HbA1c | 13 Weeks | 6.5 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.9 |
| Non-HCL and Standard Care | HbA1c | Randomization | 10.2 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.6 |
| Verapamil | HbA1c | 26 Weeks | 6.3 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.9 |
| Verapamil | HbA1c | Randomization | 10.3 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.7 |
| Verapamil | HbA1c | 13 Weeks | 6.3 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.8 |
| Verapamil | HbA1c | 39 Weeks | 6.4 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.9 |
| Verapamil | HbA1c | 52 Weeks | 6.6 Percentage of Glycosylated Hemoglobin | Standard Deviation 1 |
| Placebo | HbA1c | 39 Weeks | 7.0 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.1 |
| Placebo | HbA1c | 13 Weeks | 6.4 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.6 |
| Placebo | HbA1c | Randomization | 10.2 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.2 |
| Placebo | HbA1c | 26 Weeks | 6.5 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.8 |
| Placebo | HbA1c | 52 Weeks | 6.9 Percentage of Glycosylated Hemoglobin | Standard Deviation 1.2 |
p-value: <0.00195% CI: [-1.1, -0.3]Mixed Models Analysis
p-value: 0.6595% CI: [-1, 0.4]Mixed Models Analysis
Secondary
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
Percentage where maximum of all C-peptide values during the MMTT \>= 0.2 pmol/ml
Time frame: 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed. N missing in each group are as follows; HCL (N=1 at baseline, N=3 at 13 weeks, N=4 at 26 weeks, N=4 at 39 weeks, N=2 at 52 weeks); Non-HCL (N=0 at baseline, N=0 at 13 weeks, N=2 at 26 weeks , N=6 at 39 weeks, N=5 at 52 weeks); Verapamil (N=1 at baseline, N=1 at 13 weeks, N=2 at 26 weeks, N=4 at 39 Weeks, N=4 at 52 weeks); Placebo (N=0 at baseline, N=1 at 13 weeks, N=3 at 26 weeks, N=3 at 39 weeks, N=2 at 52 weeks).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HCL and Intensive Management | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 39 Weeks | 49 Participants |
| HCL and Intensive Management | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 13 Weeks | 58 Participants |
| HCL and Intensive Management | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 52 Weeks | 45 Participants |
| HCL and Intensive Management | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 26 Weeks | 56 Participants |
| HCL and Intensive Management | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | Randomization | 60 Participants |
| Non-HCL and Standard Care | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 26 Weeks | 47 Participants |
| Non-HCL and Standard Care | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 39 Weeks | 38 Participants |
| Non-HCL and Standard Care | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 52 Weeks | 36 Participants |
| Non-HCL and Standard Care | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 13 Weeks | 50 Participants |
| Non-HCL and Standard Care | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | Randomization | 51 Participants |
| Verapamil | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 26 Weeks | 44 Participants |
| Verapamil | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | Randomization | 46 Participants |
| Verapamil | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 13 Weeks | 45 Participants |
| Verapamil | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 39 Weeks | 41 Participants |
| Verapamil | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 52 Weeks | 41 Participants |
| Placebo | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 39 Weeks | 31 Participants |
| Placebo | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 13 Weeks | 39 Participants |
| Placebo | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | Randomization | 40 Participants |
| Placebo | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 26 Weeks | 37 Participants |
| Placebo | Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml | 52 Weeks | 27 Participants |
Secondary
Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks
Percentage of patients with \>=70% sensor glucose values from 70 to 180 mg/dL between treatment groups
Time frame: 52 Weeks
Population: N missing in each group are as follows; HCL (N=2 at 52 weeks); Non-HCL (N=4 at 52 weeks); Verapamil (N=3 at 52 weeks); Placebo (N=3 at 52 weeks).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HCL and Intensive Management | Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks | 46 Participants |
| Non-HCL and Standard Care | Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks | 22 Participants |
| Verapamil | Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks | 30 Participants |
| Placebo | Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks | 23 Participants |
p-value: <0.00195% CI: [0.21, 0.53]Regression, Logistic
p-value: 0.7995% CI: [-0.26, 0.32]Regression, Logistic
Secondary
Number of Participants With HbA1c <6.5%
Percentage of participants with HbA1c \< 6.5% between treatment groups
Time frame: 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed. N missing in each group are as follows; HCL (N=1 at baseline, N=3 at 13 weeks, N=4 at 26 weeks, N=2 at 39 weeks, N=2 at 52 weeks); Non-HCL (N=0 at baseline, N=0 at 13 weeks, N=2 at 26 weeks , N=5 at 39 weeks, N=3 at 52 weeks); Verapamil (N=0 at baseline, N=0 at 13 weeks, N=2 at 26 weeks, N=4 at 39 Weeks, N=4 at 52 weeks); Placebo (N=1 at baseline, N=1 at 13 weeks, N=3 at 26 weeks, N=1 at 39 weeks, N=1 at 52 weeks).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HCL and Intensive Management | Number of Participants With HbA1c <6.5% | 39 Weeks | 33 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <6.5% | 13 Weeks | 27 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <6.5% | 52 Weeks | 28 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <6.5% | 26 Weeks | 37 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <6.5% | Randomization | 0 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <6.5% | 26 Weeks | 23 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <6.5% | 39 Weeks | 20 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <6.5% | 52 Weeks | 19 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <6.5% | 13 Weeks | 24 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <6.5% | Randomization | 0 Participants |
| Verapamil | Number of Participants With HbA1c <6.5% | 26 Weeks | 31 Participants |
| Verapamil | Number of Participants With HbA1c <6.5% | Randomization | 0 Participants |
| Verapamil | Number of Participants With HbA1c <6.5% | 13 Weeks | 27 Participants |
| Verapamil | Number of Participants With HbA1c <6.5% | 39 Weeks | 30 Participants |
| Verapamil | Number of Participants With HbA1c <6.5% | 52 Weeks | 25 Participants |
| Placebo | Number of Participants With HbA1c <6.5% | 39 Weeks | 18 Participants |
| Placebo | Number of Participants With HbA1c <6.5% | 13 Weeks | 20 Participants |
| Placebo | Number of Participants With HbA1c <6.5% | Randomization | 0 Participants |
| Placebo | Number of Participants With HbA1c <6.5% | 26 Weeks | 22 Participants |
| Placebo | Number of Participants With HbA1c <6.5% | 52 Weeks | 18 Participants |
Secondary
Number of Participants With HbA1c <7.0%
Percentage of participants with HbA1c \< 7.0% between treatment groups
Time frame: 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed. N missing in each group are as follows; HCL (N=1 at baseline, N=3 at 13 weeks, N=4 at 26 weeks, N=2 at 39 weeks, N=2 at 52 weeks); Non-HCL (N=0 at baseline, N=0 at 13 weeks, N=2 at 26 weeks , N=5 at 39 weeks, N=3 at 52 weeks); Verapamil (N=0 at baseline, N=0 at 13 weeks, N=2 at 26 weeks, N=4 at 39 Weeks, N=4 at 52 weeks); Placebo (N=1 at baseline, N=1 at 13 weeks, N=3 at 26 weeks, N=1 at 39 weeks, N=1 at 52 weeks).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HCL and Intensive Management | Number of Participants With HbA1c <7.0% | 39 Weeks | 44 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <7.0% | 13 Weeks | 48 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <7.0% | 52 Weeks | 42 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <7.0% | 26 Weeks | 45 Participants |
| HCL and Intensive Management | Number of Participants With HbA1c <7.0% | Randomization | 2 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <7.0% | 26 Weeks | 31 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <7.0% | 39 Weeks | 23 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <7.0% | 52 Weeks | 26 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <7.0% | 13 Weeks | 36 Participants |
| Non-HCL and Standard Care | Number of Participants With HbA1c <7.0% | Randomization | 1 Participants |
| Verapamil | Number of Participants With HbA1c <7.0% | 26 Weeks | 37 Participants |
| Verapamil | Number of Participants With HbA1c <7.0% | Randomization | 3 Participants |
| Verapamil | Number of Participants With HbA1c <7.0% | 13 Weeks | 38 Participants |
| Verapamil | Number of Participants With HbA1c <7.0% | 39 Weeks | 33 Participants |
| Verapamil | Number of Participants With HbA1c <7.0% | 52 Weeks | 32 Participants |
| Placebo | Number of Participants With HbA1c <7.0% | 39 Weeks | 22 Participants |
| Placebo | Number of Participants With HbA1c <7.0% | 13 Weeks | 32 Participants |
| Placebo | Number of Participants With HbA1c <7.0% | Randomization | 0 Participants |
| Placebo | Number of Participants With HbA1c <7.0% | 26 Weeks | 25 Participants |
| Placebo | Number of Participants With HbA1c <7.0% | 52 Weeks | 23 Participants |
Secondary
Peak C-peptide
Maximum of all C-peptide values during the MMTT
Time frame: 13, 26, 39 weeks and 52 weeks
Population: 1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was excluded from the analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Peak C-peptide | 39 Weeks | 0.65 pmol/mL | Standard Deviation 0.35 |
| HCL and Intensive Management | Peak C-peptide | 13 Weeks | 0.81 pmol/mL | Standard Deviation 0.27 |
| HCL and Intensive Management | Peak C-peptide | Randomization | 0.72 pmol/mL | Standard Deviation 0.25 |
| HCL and Intensive Management | Peak C-peptide | 26 Weeks | 0.78 pmol/mL | Standard Deviation 0.34 |
| HCL and Intensive Management | Peak C-peptide | 52 Weeks | 0.56 pmol/mL | Standard Deviation 0.36 |
| Non-HCL and Standard Care | Peak C-peptide | 26 Weeks | 0.76 pmol/mL | Standard Deviation 0.33 |
| Non-HCL and Standard Care | Peak C-peptide | Randomization | 0.78 pmol/mL | Standard Deviation 0.23 |
| Non-HCL and Standard Care | Peak C-peptide | 39 Weeks | 0.69 pmol/mL | Standard Deviation 0.35 |
| Non-HCL and Standard Care | Peak C-peptide | 13 Weeks | 0.87 pmol/mL | Standard Deviation 0.29 |
| Non-HCL and Standard Care | Peak C-peptide | 52 Weeks | 0.62 pmol/mL | Standard Deviation 0.37 |
| Verapamil | Peak C-peptide | 39 Weeks | 0.89 pmol/mL | Standard Deviation 0.36 |
| Verapamil | Peak C-peptide | 52 Weeks | 0.83 pmol/mL | Standard Deviation 0.37 |
| Verapamil | Peak C-peptide | 13 Weeks | 0.84 pmol/mL | Standard Deviation 0.24 |
| Verapamil | Peak C-peptide | 26 Weeks | 0.97 pmol/mL | Standard Deviation 0.35 |
| Verapamil | Peak C-peptide | Randomization | 0.96 pmol/mL | Standard Deviation 0.3 |
| Placebo | Peak C-peptide | 52 Weeks | 0.55 pmol/mL | Standard Deviation 0.34 |
| Placebo | Peak C-peptide | 13 Weeks | 0.78 pmol/mL | Standard Deviation 0.27 |
| Placebo | Peak C-peptide | 26 Weeks | 0.76 pmol/mL | Standard Deviation 0.3 |
| Placebo | Peak C-peptide | 39 Weeks | 0.63 pmol/mL | Standard Deviation 0.32 |
| Placebo | Peak C-peptide | Randomization | 0.89 pmol/mL | Standard Deviation 0.27 |
Secondary
Percentage of CGM Time >140 mg/dL
CGM sensor glucose values \>140 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time >140 mg/dL | 39 Weeks | 38 Percent of Time | Standard Deviation 14 |
| HCL and Intensive Management | Percentage of CGM Time >140 mg/dL | 13 Weeks | 32 Percent of Time | Standard Deviation 13 |
| HCL and Intensive Management | Percentage of CGM Time >140 mg/dL | 52 Weeks | 42 Percent of Time | Standard Deviation 14 |
| HCL and Intensive Management | Percentage of CGM Time >140 mg/dL | 26 Weeks | 34 Percent of Time | Standard Deviation 13 |
| HCL and Intensive Management | Percentage of CGM Time >140 mg/dL | 6 Weeks | 29 Percent of Time | Standard Deviation 11 |
| Non-HCL and Standard Care | Percentage of CGM Time >140 mg/dL | 26 Weeks | 47 Percent of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time >140 mg/dL | 39 Weeks | 53 Percent of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time >140 mg/dL | 52 Weeks | 56 Percent of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time >140 mg/dL | 13 Weeks | 40 Percent of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time >140 mg/dL | 6 Weeks | 38 Percent of Time | Standard Deviation 23 |
| Verapamil | Percentage of CGM Time >140 mg/dL | 26 Weeks | 36 Percent of Time | Standard Deviation 20 |
| Verapamil | Percentage of CGM Time >140 mg/dL | 6 Weeks | 32 Percent of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time >140 mg/dL | 13 Weeks | 34 Percent of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time >140 mg/dL | 39 Weeks | 40 Percent of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time >140 mg/dL | 52 Weeks | 47 Percent of Time | Standard Deviation 19 |
| Placebo | Percentage of CGM Time >140 mg/dL | 39 Weeks | 47 Percent of Time | Standard Deviation 21 |
| Placebo | Percentage of CGM Time >140 mg/dL | 13 Weeks | 33 Percent of Time | Standard Deviation 20 |
| Placebo | Percentage of CGM Time >140 mg/dL | 6 Weeks | 32 Percent of Time | Standard Deviation 18 |
| Placebo | Percentage of CGM Time >140 mg/dL | 26 Weeks | 41 Percent of Time | Standard Deviation 20 |
| Placebo | Percentage of CGM Time >140 mg/dL | 52 Weeks | 49 Percent of Time | Standard Deviation 22 |
Secondary
Percentage of CGM Time >180 mg/dL
CGM sensor glucose values \>180 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time >180 mg/dL | 39 Weeks | 18 Percent of Time | Standard Deviation 11 |
| HCL and Intensive Management | Percentage of CGM Time >180 mg/dL | 13 Weeks | 14 Percent of Time | Standard Deviation 9 |
| HCL and Intensive Management | Percentage of CGM Time >180 mg/dL | 52 Weeks | 20 Percent of Time | Standard Deviation 11 |
| HCL and Intensive Management | Percentage of CGM Time >180 mg/dL | 26 Weeks | 15 Percent of Time | Standard Deviation 10 |
| HCL and Intensive Management | Percentage of CGM Time >180 mg/dL | 6 Weeks | 12 Percent of Time | Standard Deviation 8 |
| Non-HCL and Standard Care | Percentage of CGM Time >180 mg/dL | 26 Weeks | 25 Percent of Time | Standard Deviation 20 |
| Non-HCL and Standard Care | Percentage of CGM Time >180 mg/dL | 39 Weeks | 30 Percent of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time >180 mg/dL | 52 Weeks | 34 Percent of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time >180 mg/dL | 13 Weeks | 19 Percent of Time | Standard Deviation 17 |
| Non-HCL and Standard Care | Percentage of CGM Time >180 mg/dL | 6 Weeks | 19 Percent of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time >180 mg/dL | 26 Weeks | 17 Percent of Time | Standard Deviation 17 |
| Verapamil | Percentage of CGM Time >180 mg/dL | 6 Weeks | 13 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time >180 mg/dL | 13 Weeks | 15 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time >180 mg/dL | 39 Weeks | 19 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time >180 mg/dL | 52 Weeks | 25 Percent of Time | Standard Deviation 18 |
| Placebo | Percentage of CGM Time >180 mg/dL | 39 Weeks | 26 Percent of Time | Standard Deviation 21 |
| Placebo | Percentage of CGM Time >180 mg/dL | 13 Weeks | 15 Percent of Time | Standard Deviation 14 |
| Placebo | Percentage of CGM Time >180 mg/dL | 6 Weeks | 14 Percent of Time | Standard Deviation 14 |
| Placebo | Percentage of CGM Time >180 mg/dL | 26 Weeks | 21 Percent of Time | Standard Deviation 18 |
| Placebo | Percentage of CGM Time >180 mg/dL | 52 Weeks | 28 Percent of Time | Standard Deviation 21 |
p-value: <0.00195% CI: [-22, -9]Mixed Models Analysis
p-value: 0.7495% CI: [-13, 9]Mixed Models Analysis
Secondary
Percentage of CGM Time >250 mg/dL
Percentage of CGM sensor glucose values \>250 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time >250 mg/dL | 39 Weeks | 3 Percent of Time | Standard Deviation 3 |
| HCL and Intensive Management | Percentage of CGM Time >250 mg/dL | 13 Weeks | 2 Percent of Time | Standard Deviation 3 |
| HCL and Intensive Management | Percentage of CGM Time >250 mg/dL | 52 Weeks | 4 Percent of Time | Standard Deviation 4 |
| HCL and Intensive Management | Percentage of CGM Time >250 mg/dL | 26 Weeks | 2 Percent of Time | Standard Deviation 3 |
| HCL and Intensive Management | Percentage of CGM Time >250 mg/dL | 6 Weeks | 1 Percent of Time | Standard Deviation 2 |
| Non-HCL and Standard Care | Percentage of CGM Time >250 mg/dL | 26 Weeks | 6 Percent of Time | Standard Deviation 8 |
| Non-HCL and Standard Care | Percentage of CGM Time >250 mg/dL | 39 Weeks | 9 Percent of Time | Standard Deviation 12 |
| Non-HCL and Standard Care | Percentage of CGM Time >250 mg/dL | 52 Weeks | 10 Percent of Time | Standard Deviation 13 |
| Non-HCL and Standard Care | Percentage of CGM Time >250 mg/dL | 13 Weeks | 3 Percent of Time | Standard Deviation 4 |
| Non-HCL and Standard Care | Percentage of CGM Time >250 mg/dL | 6 Weeks | 3 Percent of Time | Standard Deviation 4 |
| Verapamil | Percentage of CGM Time >250 mg/dL | 26 Weeks | 2 Percent of Time | Standard Deviation 3 |
| Verapamil | Percentage of CGM Time >250 mg/dL | 6 Weeks | 1 Percent of Time | Standard Deviation 1 |
| Verapamil | Percentage of CGM Time >250 mg/dL | 13 Weeks | 2 Percent of Time | Standard Deviation 2 |
| Verapamil | Percentage of CGM Time >250 mg/dL | 39 Weeks | 3 Percent of Time | Standard Deviation 4 |
| Verapamil | Percentage of CGM Time >250 mg/dL | 52 Weeks | 5 Percent of Time | Standard Deviation 6 |
| Placebo | Percentage of CGM Time >250 mg/dL | 39 Weeks | 7 Percent of Time | Standard Deviation 9 |
| Placebo | Percentage of CGM Time >250 mg/dL | 13 Weeks | 2 Percent of Time | Standard Deviation 3 |
| Placebo | Percentage of CGM Time >250 mg/dL | 6 Weeks | 2 Percent of Time | Standard Deviation 3 |
| Placebo | Percentage of CGM Time >250 mg/dL | 26 Weeks | 4 Percent of Time | Standard Deviation 6 |
| Placebo | Percentage of CGM Time >250 mg/dL | 52 Weeks | 8 Percent of Time | Standard Deviation 10 |
p-value: 0.00395% CI: [-7, -1]Mixed Models Analysis
p-value: 0.7495% CI: [-6, 4]Mixed Models Analysis
Secondary
Percentage of CGM Time <54 mg/dL
Percentage of CGM sensor glucose values \<54 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time <54 mg/dL | 39 Weeks | 0.32 Percent of Time | Standard Error 0.34 |
| HCL and Intensive Management | Percentage of CGM Time <54 mg/dL | 13 Weeks | 0.23 Percent of Time | Standard Error 0.21 |
| HCL and Intensive Management | Percentage of CGM Time <54 mg/dL | 52 Weeks | 0.29 Percent of Time | Standard Error 0.34 |
| HCL and Intensive Management | Percentage of CGM Time <54 mg/dL | 26 Weeks | 0.25 Percent of Time | Standard Error 0.25 |
| HCL and Intensive Management | Percentage of CGM Time <54 mg/dL | 6 Weeks | 0.22 Percent of Time | Standard Error 0.22 |
| Non-HCL and Standard Care | Percentage of CGM Time <54 mg/dL | 26 Weeks | 0.10 Percent of Time | Standard Error 0.11 |
| Non-HCL and Standard Care | Percentage of CGM Time <54 mg/dL | 39 Weeks | 0.16 Percent of Time | Standard Error 0.2 |
| Non-HCL and Standard Care | Percentage of CGM Time <54 mg/dL | 52 Weeks | 0.18 Percent of Time | Standard Error 0.21 |
| Non-HCL and Standard Care | Percentage of CGM Time <54 mg/dL | 13 Weeks | 0.12 Percent of Time | Standard Error 0.16 |
| Non-HCL and Standard Care | Percentage of CGM Time <54 mg/dL | 6 Weeks | 0.11 Percent of Time | Standard Error 0.13 |
| Verapamil | Percentage of CGM Time <54 mg/dL | 26 Weeks | 0.22 Percent of Time | Standard Error 0.25 |
| Verapamil | Percentage of CGM Time <54 mg/dL | 6 Weeks | 0.14 Percent of Time | Standard Error 0.16 |
| Verapamil | Percentage of CGM Time <54 mg/dL | 13 Weeks | 0.19 Percent of Time | Standard Error 0.2 |
| Verapamil | Percentage of CGM Time <54 mg/dL | 39 Weeks | 0.21 Percent of Time | Standard Error 0.27 |
| Verapamil | Percentage of CGM Time <54 mg/dL | 52 Weeks | 0.20 Percent of Time | Standard Error 0.24 |
| Placebo | Percentage of CGM Time <54 mg/dL | 39 Weeks | 0.26 Percent of Time | Standard Error 0.27 |
| Placebo | Percentage of CGM Time <54 mg/dL | 13 Weeks | 0.16 Percent of Time | Standard Error 0.19 |
| Placebo | Percentage of CGM Time <54 mg/dL | 6 Weeks | 0.16 Percent of Time | Standard Error 0.16 |
| Placebo | Percentage of CGM Time <54 mg/dL | 26 Weeks | 0.14 Percent of Time | Standard Error 0.18 |
| Placebo | Percentage of CGM Time <54 mg/dL | 52 Weeks | 0.24 Percent of Time | Standard Error 0.26 |
p-value: 0.2395% CI: [-0.04, 0.17]Regression, Linear
p-value: 0.7995% CI: [-1, 0.6]Regression, Linear
Secondary
Percentage of CGM Time <70 mg/dL
Percentage of CGM sensor glucose values \<70 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time <70 mg/dL | 13 Weeks | 1.6 Percent of Time | Standard Deviation 1.2 |
| HCL and Intensive Management | Percentage of CGM Time <70 mg/dL | 6 Weeks | 1.7 Percent of Time | Standard Deviation 1 |
| HCL and Intensive Management | Percentage of CGM Time <70 mg/dL | 52 Weeks | 1.8 Percent of Time | Standard Deviation 1.2 |
| HCL and Intensive Management | Percentage of CGM Time <70 mg/dL | 26 Weeks | 1.9 Percent of Time | Standard Deviation 1.1 |
| HCL and Intensive Management | Percentage of CGM Time <70 mg/dL | 39 Weeks | 2.0 Percent of Time | Standard Deviation 1.3 |
| Non-HCL and Standard Care | Percentage of CGM Time <70 mg/dL | 26 Weeks | 1.2 Percent of Time | Standard Deviation 1 |
| Non-HCL and Standard Care | Percentage of CGM Time <70 mg/dL | 39 Weeks | 1.2 Percent of Time | Standard Deviation 1.3 |
| Non-HCL and Standard Care | Percentage of CGM Time <70 mg/dL | 52 Weeks | 1.4 Percent of Time | Standard Deviation 1.4 |
| Non-HCL and Standard Care | Percentage of CGM Time <70 mg/dL | 13 Weeks | 1.2 Percent of Time | Standard Deviation 1.1 |
| Non-HCL and Standard Care | Percentage of CGM Time <70 mg/dL | 6 Weeks | 1.5 Percent of Time | Standard Deviation 1.6 |
| Verapamil | Percentage of CGM Time <70 mg/dL | 26 Weeks | 1.6 Percent of Time | Standard Deviation 1.4 |
| Verapamil | Percentage of CGM Time <70 mg/dL | 6 Weeks | 1.5 Percent of Time | Standard Deviation 1.5 |
| Verapamil | Percentage of CGM Time <70 mg/dL | 13 Weeks | 1.4 Percent of Time | Standard Deviation 0.9 |
| Verapamil | Percentage of CGM Time <70 mg/dL | 39 Weeks | 1.5 Percent of Time | Standard Deviation 1.4 |
| Verapamil | Percentage of CGM Time <70 mg/dL | 52 Weeks | 1.3 Percent of Time | Standard Deviation 1.2 |
| Placebo | Percentage of CGM Time <70 mg/dL | 39 Weeks | 1.7 Percent of Time | Standard Deviation 1.6 |
| Placebo | Percentage of CGM Time <70 mg/dL | 13 Weeks | 1.4 Percent of Time | Standard Deviation 1.5 |
| Placebo | Percentage of CGM Time <70 mg/dL | 6 Weeks | 1.7 Percent of Time | Standard Deviation 1.6 |
| Placebo | Percentage of CGM Time <70 mg/dL | 26 Weeks | 1.4 Percent of Time | Standard Deviation 1.2 |
| Placebo | Percentage of CGM Time <70 mg/dL | 52 Weeks | 1.6 Percent of Time | Standard Deviation 1.3 |
p-value: 0.3995% CI: [-0.3, 0.7]Regression, Linear
p-value: 0.7495% CI: [-1, 0.6]Regression, Linear
Secondary
Percentage of CGM Time in Range 70-140 mg/dL
Percentage of CGM sensor glucose values from 70 to 140 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time in Range 70-140 mg/dL | 39 Weeks | 60 Percentage of Time | Standard Deviation 14 |
| HCL and Intensive Management | Percentage of CGM Time in Range 70-140 mg/dL | 13 Weeks | 67 Percentage of Time | Standard Deviation 13 |
| HCL and Intensive Management | Percentage of CGM Time in Range 70-140 mg/dL | 52 Weeks | 56 Percentage of Time | Standard Deviation 13 |
| HCL and Intensive Management | Percentage of CGM Time in Range 70-140 mg/dL | 26 Weeks | 64 Percentage of Time | Standard Deviation 13 |
| HCL and Intensive Management | Percentage of CGM Time in Range 70-140 mg/dL | 6 Weeks | 69 Percentage of Time | Standard Deviation 11 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range 70-140 mg/dL | 26 Weeks | 51 Percentage of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range 70-140 mg/dL | 39 Weeks | 46 Percentage of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range 70-140 mg/dL | 52 Weeks | 43 Percentage of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range 70-140 mg/dL | 13 Weeks | 59 Percentage of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range 70-140 mg/dL | 6 Weeks | 60 Percentage of Time | Standard Deviation 22 |
| Verapamil | Percentage of CGM Time in Range 70-140 mg/dL | 26 Weeks | 61 Percentage of Time | Standard Deviation 20 |
| Verapamil | Percentage of CGM Time in Range 70-140 mg/dL | 6 Weeks | 67 Percentage of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time in Range 70-140 mg/dL | 13 Weeks | 65 Percentage of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time in Range 70-140 mg/dL | 39 Weeks | 58 Percentage of Time | Standard Deviation 19 |
| Verapamil | Percentage of CGM Time in Range 70-140 mg/dL | 52 Weeks | 51 Percentage of Time | Standard Deviation 19 |
| Placebo | Percentage of CGM Time in Range 70-140 mg/dL | 39 Weeks | 51 Percentage of Time | Standard Deviation 20 |
| Placebo | Percentage of CGM Time in Range 70-140 mg/dL | 13 Weeks | 65 Percentage of Time | Standard Deviation 19 |
| Placebo | Percentage of CGM Time in Range 70-140 mg/dL | 6 Weeks | 66 Percentage of Time | Standard Deviation 18 |
| Placebo | Percentage of CGM Time in Range 70-140 mg/dL | 26 Weeks | 57 Percentage of Time | Standard Deviation 19 |
| Placebo | Percentage of CGM Time in Range 70-140 mg/dL | 52 Weeks | 49 Percentage of Time | Standard Deviation 21 |
p-value: <0.00195% CI: [10, 22]Mixed Models Analysis
p-value: 0.9595% CI: [-8, 14]Mixed Models Analysis
Secondary
Percentage of CGM Time in Range (70-180 mg/dL)
CGM sensor glucose values from 70 to 180 mg/dL between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Percentage of CGM Time in Range (70-180 mg/dL) | 39 Weeks | 80 Percent of Time | Standard Deviation 11 |
| HCL and Intensive Management | Percentage of CGM Time in Range (70-180 mg/dL) | 13 Weeks | 84 Percent of Time | Standard Deviation 9 |
| HCL and Intensive Management | Percentage of CGM Time in Range (70-180 mg/dL) | 52 Weeks | 78 Percent of Time | Standard Deviation 11 |
| HCL and Intensive Management | Percentage of CGM Time in Range (70-180 mg/dL) | 26 Weeks | 83 Percent of Time | Standard Deviation 10 |
| HCL and Intensive Management | Percentage of CGM Time in Range (70-180 mg/dL) | 6 Weeks | 86 Percent of Time | Standard Deviation 8 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range (70-180 mg/dL) | 26 Weeks | 73 Percent of Time | Standard Deviation 20 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range (70-180 mg/dL) | 39 Weeks | 68 Percent of Time | Standard Deviation 21 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range (70-180 mg/dL) | 52 Weeks | 64 Percent of Time | Standard Deviation 22 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range (70-180 mg/dL) | 13 Weeks | 79 Percent of Time | Standard Deviation 16 |
| Non-HCL and Standard Care | Percentage of CGM Time in Range (70-180 mg/dL) | 6 Weeks | 84 Percent of Time | Standard Deviation 9 |
| Verapamil | Percentage of CGM Time in Range (70-180 mg/dL) | 26 Weeks | 81 Percent of Time | Standard Deviation 17 |
| Verapamil | Percentage of CGM Time in Range (70-180 mg/dL) | 6 Weeks | 85 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time in Range (70-180 mg/dL) | 13 Weeks | 83 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time in Range (70-180 mg/dL) | 39 Weeks | 80 Percent of Time | Standard Deviation 15 |
| Verapamil | Percentage of CGM Time in Range (70-180 mg/dL) | 52 Weeks | 74 Percent of Time | Standard Deviation 18 |
| Placebo | Percentage of CGM Time in Range (70-180 mg/dL) | 39 Weeks | 72 Percent of Time | Standard Deviation 20 |
| Placebo | Percentage of CGM Time in Range (70-180 mg/dL) | 13 Weeks | 84 Percent of Time | Standard Deviation 13 |
| Placebo | Percentage of CGM Time in Range (70-180 mg/dL) | 6 Weeks | 84 Percent of Time | Standard Deviation 13 |
| Placebo | Percentage of CGM Time in Range (70-180 mg/dL) | 26 Weeks | 78 Percent of Time | Standard Deviation 17 |
| Placebo | Percentage of CGM Time in Range (70-180 mg/dL) | 52 Weeks | 70 Percent of Time | Standard Deviation 21 |
p-value: <0.00195% CI: [10, 22]Mixed Models Analysis
p-value: 0.7495% CI: [-9, 13]Mixed Models Analysis
Secondary
Severe Hypoglycemia
Frequency of episodes of severe hypoglycemia between treatment groups
Time frame: 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCL and Intensive Management | Severe Hypoglycemia | 1 Number of Severe Hypoglycemic Events |
| Non-HCL and Standard Care | Severe Hypoglycemia | 1 Number of Severe Hypoglycemic Events |
| Verapamil | Severe Hypoglycemia | 1 Number of Severe Hypoglycemic Events |
| Placebo | Severe Hypoglycemia | 1 Number of Severe Hypoglycemic Events |
Secondary
Total Daily Insulin Per kg
Total daily insulin per kg between treatment groups
Time frame: 6, 13, 26, 39 weeks and 52 weeks
Population: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HCL and Intensive Management | Total Daily Insulin Per kg | Randomization | 0.68 U/kg/day | Standard Deviation 0.28 |
| HCL and Intensive Management | Total Daily Insulin Per kg | 6 Weeks | 0.54 U/kg/day | Standard Deviation 0.26 |
| HCL and Intensive Management | Total Daily Insulin Per kg | 13 Weeks | 0.51 U/kg/day | Standard Deviation 0.23 |
| HCL and Intensive Management | Total Daily Insulin Per kg | 26 Weeks | 0.61 U/kg/day | Standard Deviation 0.28 |
| HCL and Intensive Management | Total Daily Insulin Per kg | 39 Weeks | 0.68 U/kg/day | Standard Deviation 0.32 |
| HCL and Intensive Management | Total Daily Insulin Per kg | 52 Weeks | 0.74 U/kg/day | Standard Deviation 0.32 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | 52 Weeks | 0.64 U/kg/day | Standard Deviation 0.25 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | 26 Weeks | 0.53 U/kg/day | Standard Deviation 0.23 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | Randomization | 0.66 U/kg/day | Standard Deviation 0.3 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | 13 Weeks | 0.53 U/kg/day | Standard Deviation 0.25 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | 6 Weeks | 0.55 U/kg/day | Standard Deviation 0.33 |
| Non-HCL and Standard Care | Total Daily Insulin Per kg | 39 Weeks | 0.58 U/kg/day | Standard Deviation 0.27 |
| Verapamil | Total Daily Insulin Per kg | 6 Weeks | 0.55 U/kg/day | Standard Deviation 0.33 |
| Verapamil | Total Daily Insulin Per kg | 13 Weeks | 0.54 U/kg/day | Standard Deviation 0.25 |
| Verapamil | Total Daily Insulin Per kg | 26 Weeks | 0.57 U/kg/day | Standard Deviation 0.28 |
| Verapamil | Total Daily Insulin Per kg | 52 Weeks | 0.65 U/kg/day | Standard Deviation 0.26 |
| Verapamil | Total Daily Insulin Per kg | 39 Weeks | 0.59 U/kg/day | Standard Deviation 0.29 |
| Verapamil | Total Daily Insulin Per kg | Randomization | 0.74 U/kg/day | Standard Deviation 0.29 |
| Placebo | Total Daily Insulin Per kg | 39 Weeks | 0.66 U/kg/day | Standard Deviation 0.32 |
| Placebo | Total Daily Insulin Per kg | 52 Weeks | 0.74 U/kg/day | Standard Deviation 0.34 |
| Placebo | Total Daily Insulin Per kg | 6 Weeks | 0.54 U/kg/day | Standard Deviation 0.28 |
| Placebo | Total Daily Insulin Per kg | 26 Weeks | 0.58 U/kg/day | Standard Deviation 0.29 |
| Placebo | Total Daily Insulin Per kg | Randomization | 0.64 U/kg/day | Standard Deviation 0.27 |
| Placebo | Total Daily Insulin Per kg | 13 Weeks | 0.54 U/kg/day | Standard Deviation 0.26 |
p-value: 0.0795% CI: [-0.01, 0.2]Mixed Models Analysis
p-value: 0.5295% CI: [-0.3, 0.05]Mixed Models Analysis