Hybrid Closed Loop Therapy and Verapamil for Beta Cell Pr... | NCT04233034

NCT04233034

Status Module

Sponsor/Collaborators Module

Name	Class
Juvenile Diabetes Research Foundation	OTHER
University of Minnesota	OTHER
DexCom, Inc.	INDUSTRY
Medtronic

Oversight Module

Description Module

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.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
HCL and placebo	Active Comparator	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.]	Device: HCL Drug: placebo
HCL and verapamil	Active Comparator	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.]	Device: HCL Drug: verapamil 120mg tablet
non-HCL and verapamil	Active Comparator	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.]

Name	Type	Description	Arm Group Labels	Other Names
HCL	Device	Hybrid Closed Loop therapy	HCL and placebo HCL and verapamil

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	52 weeks

Secondary Outcomes

Measure	Description	Time Frame
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.	13, 26 and 39 weeks

Eligibility Module

Eligibility 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 exclusion criteria for Cohort A:
1. Blood pressure (either systolic or diastolic) <5th percentile for age, gender, and height on two out of three measurements
2. Pulse <2nd percentile for age and gender on two out of three measurements
3. History of vasovagal syncopal episodes related to hypotension
4. Abnormal EKG rhythm unless cleared for study participation by a cardiologist
5. Underlying cardiac disease (ex. left ventricular dysfunction, hypertrophic cardiomyopathy), certain arrhythmias (ex. Atrioventricular block (AV) block, accessory pathway such as Wolff-Parkinson-White or Lown-Ganong-Levine syndromes), known liver dysfunction, known renal impairment, Duchenne's muscular dystrophy, active Graves disease or hyperthyroidism, and untreated hypothyroidism
6. Estimated glomerular filtration rate (eGFR) < 90
7. AST and/or ALT greater than 1.5 times the upper limit of normal
8. Need to use of any of the following medications during the study: beta blocker, seizure medication (carbamazepine, phenobarbital, phenytoin), other antihypertensive medications, HMG-CoA reductase inhibitors, lithium, theophylline, clonidine, or aspirin
9. Any known hypersensitivity reaction to Verapamil

Contacts/Locations Module

Name	Affiliation	Role
Antoinette Moran, MD	University of Minnesota	Study Chair
Gregory Forlenza, MD	Barbara Davis Center	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Stanford University		Palo Alto	California	94304	United States
Barbara Davis Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38860154	Derived	Ekhlaspour L, Buckingham B, Bauza C, Clements M, Forlenza GP, Neyman A, Norlander L, Schamberger M, Sherr JL, Bailey R, Beck RW, Kollman C, Beasley S, Cobry E, DiMeglio LA, Paprocki E, Van Name M, Moran A; CLVer Study Group. Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience. J Clin Transl Endocrinol. 2024 May 18;36:100352. doi: 10.1016/j.jcte.2024.100352. eCollection 2024 Jun.
36826844

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 1, 2022	Mar 15, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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
BG001	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
BG002	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
BG003	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
BG004	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
BG005	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
BG006	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG00225 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
Race/Ethnicity	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Annual Household Income

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Highest Parental Education

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Health Insurance

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

BMI Percentile at Randomization

1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.

Median

Inter-Quartile Range

Percentile

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Time Since Diagnosis at Randomization (days)

Mean

Standard Deviation

Days

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Lab HbA1c at Randomization (%)

1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.

Mean

Standard Deviation

Percentage of glycosylated hemoglobin

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00119 ParticipantsBG002

Systolic Blood Pressure at Randomization (mmHg)

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Diastolic Blood Pressure at Randomization (mmHg)

Mean

Standard Deviation

mmHg

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

DKA at Diagnosis

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Tanner Staging

Tanner stages assess pubertal development in adolescents. Higher stages indicate more advanced pubertal development. Stages are determined by the pubic hair scale for both males and females, the female breast development scale, and the male external genitalia scale.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00022 ParticipantsBG00120 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Geometric Mean

Standard Deviation

(pmol/ml)*minutes

52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil	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
OG003	Placebo	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.] placebo: placebo pill manufactured to mimic verapamil 120mg tablet

Units	Counts
Participants	OG00061 OG00151 OG00247 OG003

Title

Denominators

Categories

Randomization

Title	Measurements
	OG0000.57± 0.22 OG0010.60± 0.18 OG0020.66± 0.20 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	The model included age, days from T1D diagnosis to randomization, and drug group as fixed effects and clinical site as a random effect.	0.89		Mean Difference (Final Values)	-0.01			2-Sided	95	-0.11	0.10			Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.		Superiority

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.

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.

Posted

Geometric Mean

Standard Deviation

(pmol/ml)*minutes

13, 26 and 39 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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

Secondary

Peak C-peptide

Maximum of all C-peptide values during the MMTT

1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was excluded from the analyses.

Posted

Mean

Standard Deviation

pmol/mL

13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

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

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).

Posted

Count of Participants

Participants

13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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

Secondary

CGM Mean Glucose

Mean glucose between treatment groups

1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.

Posted

Mean

Standard Deviation

mg/dL

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Percentage of CGM Time in Range (70-180 mg/dL)

CGM sensor glucose values from 70 to 180 mg/dL between treatment groups

1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.

Posted

Mean

Standard Deviation

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

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

1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.

Posted

Mean

Standard Deviation

Percentage of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

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

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).

Posted

Count of Participants

Participants

52 Weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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

Secondary

Percentage of CGM Time >140 mg/dL

CGM sensor glucose values >140 mg/dL between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Percentage of CGM Time >180 mg/dL

CGM sensor glucose values >180 mg/dL between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Percentage of CGM Time >250 mg/dL

Percentage of CGM sensor glucose values >250 mg/dL between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Percentage of CGM Time <54 mg/dL

Percentage of CGM sensor glucose values <54 mg/dL between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Error

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Percentage of CGM Time <70 mg/dL

Percentage of CGM sensor glucose values <70 mg/dL between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Percent of Time

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

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.

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Coefficient of Variation Percentage

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002

Secondary

HbA1c

HbA1c between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

Percentage of Glycosylated Hemoglobin

13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Number of Participants With HbA1c <7.0%

Percentage of participants with HbA1c < 7.0% between treatment groups

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).

Posted

Count of Participants

Participants

13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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

Secondary

Number of Participants With HbA1c <6.5%

Percentage of participants with HbA1c < 6.5% between treatment groups

Posted

Count of Participants

Participants

13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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

Secondary

Total Daily Insulin Per kg

Total daily insulin per kg between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Mean

Standard Deviation

U/kg/day

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Basal:Bolus Ratio

Ratio of basal:bolus insulin between treatment groups

1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.

Posted

Number

Daily Basal/Bolus Ratio

6, 13, 26, 39 weeks and 52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil

Secondary

Severe Hypoglycemia

Frequency of episodes of severe hypoglycemia between treatment groups

Posted

Number

Number of Severe Hypoglycemic Events

52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil	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

Secondary

DKA

Frequency of episodes of DKA between treatment groups

Posted

Number

Number of DKA Events

52 weeks

ID	Title	Description
OG000	HCL and Intensive Management	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. [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
OG001	Non-HCL and Standard Care	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. [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
OG002	Verapamil	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

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	3	22	20	22
EG001	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	1	20	16	20
EG002	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	1	25	19	25
EG003	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	3	21	14	21
EG004	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	1	19	18	19
EG005	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	0	6	4	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Suicidal Ideation	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected22 at risk EG0010 events0 affected20 at risk EG0023 events1 affected25 at risk EG0031 events1 affected21 at risk EG0040 events0 affected19 at risk EG0050 events0 affected6 at risk
Depression	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Hypoglycemia	Endocrine disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Diabetic Ketoacidosis	Endocrine disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Ketosis	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG0031 events1 affected21 at risk EG0040 events0 affected19 at risk EG0050 events0 affected6 at risk
Swollen Glands	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
2nd Degree Heart Block	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Cardiac Arrhythmia	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
1st Degree Heart Block	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Premature Ventricular Contractions	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Ear Infection	Ear and labyrinth disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Otitis Externa	Ear and labyrinth disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Otitis Media Acute	Ear and labyrinth disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Pain in Ear	Ear and labyrinth disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Hyperglycemia	Endocrine disorders	MedDRA (10.0)	Non-systematic Assessment	EG0006 events3 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Thyroiditis	Endocrine disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0012 events2 affected20 at risk EG0020 events0 affected25 at risk EG003
Acid Indegestion	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Bloody Stool	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Celiac Disease	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0022 events2 affected25 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Gastroenteritis	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Hyperemesis	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Stomach Pain	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Stomach Virus	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Tooth Infection	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Upset Stomach	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Catheter Site Pain	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Chest Pain	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Fatigue	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Fever	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0022 events2 affected25 at risk EG003
Malaise	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Pain NOS	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Swelling of Feet	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Allergy NOS	Immune system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Hives	Immune system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Seasonal Allergy	Immune system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Vitiligo	Immune system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Covid-19	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0003 events3 affected22 at risk EG0014 events4 affected20 at risk EG0027 events6 affected25 at risk EG003
Influenza	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Tinea Pedis	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Viral Syndrome	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0003 events2 affected22 at risk EG0011 events1 affected20 at risk EG0021 events1 affected25 at risk EG003
Animal Bite	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Foot Injury	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Motor Vehicle Accident	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0012 events2 affected20 at risk EG0020 events0 affected25 at risk EG003
Elevated Liver Enzymes	Investigations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0022 events2 affected25 at risk EG003
Heart Murmur	Investigations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Abnormal Weight Gain	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Ketosis	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0012 events1 affected20 at risk EG0022 events2 affected25 at risk EG003
Vitamin D Deficiency	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Arm Fracture	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Foot Pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Leg Cramps	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Leg Pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Muscle Cramps	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Pain in Elbow	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Sprained Ankle	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Temporomandibular Joint Disorder	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Wrist Fracture	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Autism	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Headache	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0004 events3 affected22 at risk EG0014 events3 affected20 at risk EG0021 events1 affected25 at risk EG003
Numbness in Feet	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Paresthesia	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Pre-syncope	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Tingling Sensation	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Vasovagal Attack	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Adjustment Disorder	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0022 events2 affected25 at risk EG003
Depression	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0022 events2 affected25 at risk EG003
Panic Attack	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0022 events2 affected25 at risk EG003
Urinary Tract Infection	Renal and urinary disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0024 events3 affected25 at risk EG003
Allergic Rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Cold	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0023 events3 affected25 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Postnasal Drip	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Respiratory Infection	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Runny Nose	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Sinus Infection	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Sinusitis	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Sore Throat	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0003 events2 affected22 at risk EG0010 events0 affected20 at risk EG0022 events2 affected25 at risk EG003
Streptococcal Sore Throat	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Upper Respiratory Infection	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0003 events3 affected22 at risk EG0015 events5 affected20 at risk EG0021 events1 affected25 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Bruise	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Contact Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Ingrown toe nail	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Lipohypertrophy	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Skin Abrasion	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Skin Bacterial Infection	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Skin Disorder NOS	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0021 events1 affected25 at risk EG003
Skin Infection	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0011 events1 affected20 at risk EG0021 events1 affected25 at risk EG003
Tinea Corporis	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003
Tooth Extraction	Surgical and medical procedures	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0021 events1 affected25 at risk EG003
Benign Essential Hypertension	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0010 events0 affected20 at risk EG0021 events1 affected25 at risk EG003
Hypotension	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events1 affected22 at risk EG0010 events0 affected20 at risk EG0020 events0 affected25 at risk EG003
Syncope	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected20 at risk EG0020 events0 affected25 at risk EG003

First MCP Posted Date

ID	Term
D007943	Leukemia, Hairy Cell
D003920	Diabetes Mellitus

Ancestor Terms

ID	Term
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D014700	Verapamil
D013607	Tablets

ParticipantsBG006113

ParticipantsBG006112

ParticipantsBG006113

ParticipantsBG006111

ParticipantsBG006113

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

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

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

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

EG0040 events0 affected19 at risk