Trial Outcomes & Findings for Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes (NCT NCT04233034)
NCT ID: NCT04233034
Last Updated: 2024-11-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
113 participants
Primary outcome timeframe
52 weeks
Results posted on
2024-11-27
Participant Flow
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
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
|
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
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
20
|
22
|
25
|
21
|
19
|
6
|
|
Overall Study
COMPLETED
|
20
|
21
|
23
|
19
|
19
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
2
|
2
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
Baseline characteristics by cohort
| Measure |
HCL and Verapamil
n=22 Participants
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
|
HCL and Placebo
n=20 Participants
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
|
Non-HCL and Verapamil
n=25 Participants
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
|
Non-HCL and Placebo
n=21 Participants
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
|
HCL Only
n=19 Participants
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
|
Non-HCL Only
n=6 Participants
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
|
Total
n=113 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
13 years
STANDARD_DEVIATION 3 • n=22 Participants
|
12 years
STANDARD_DEVIATION 2 • n=20 Participants
|
13 years
STANDARD_DEVIATION 3 • n=25 Participants
|
13 years
STANDARD_DEVIATION 2 • n=21 Participants
|
8 years
STANDARD_DEVIATION 1 • n=19 Participants
|
9 years
STANDARD_DEVIATION 1 • n=6 Participants
|
12 years
STANDARD_DEVIATION 3 • n=113 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=22 Participants
|
9 Participants
n=20 Participants
|
12 Participants
n=25 Participants
|
7 Participants
n=21 Participants
|
10 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
49 Participants
n=113 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=22 Participants
|
11 Participants
n=20 Participants
|
13 Participants
n=25 Participants
|
14 Participants
n=21 Participants
|
9 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
64 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · White
|
16 Participants
n=22 Participants
|
14 Participants
n=20 Participants
|
20 Participants
n=25 Participants
|
15 Participants
n=21 Participants
|
15 Participants
n=19 Participants
|
6 Participants
n=6 Participants
|
86 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Black/African American
|
1 Participants
n=22 Participants
|
1 Participants
n=20 Participants
|
1 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
4 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Hispanic
|
4 Participants
n=22 Participants
|
2 Participants
n=20 Participants
|
4 Participants
n=25 Participants
|
4 Participants
n=21 Participants
|
1 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
15 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Asian
|
0 Participants
n=22 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
1 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · American Indian/Alaskan Native
|
1 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
1 Participants
n=113 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · More than One
|
0 Participants
n=22 Participants
|
2 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
6 Participants
n=113 Participants
|
|
Annual Household Income
<$50,000
|
5 Participants
n=22 Participants
|
3 Participants
n=20 Participants
|
5 Participants
n=25 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
17 Participants
n=113 Participants
|
|
Annual Household Income
$50,000-<$100,000
|
5 Participants
n=22 Participants
|
3 Participants
n=20 Participants
|
4 Participants
n=25 Participants
|
6 Participants
n=21 Participants
|
5 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
26 Participants
n=113 Participants
|
|
Annual Household Income
>=$100,000
|
12 Participants
n=22 Participants
|
12 Participants
n=20 Participants
|
15 Participants
n=25 Participants
|
8 Participants
n=21 Participants
|
12 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
62 Participants
n=113 Participants
|
|
Annual Household Income
Missing
|
0 Participants
n=22 Participants
|
2 Participants
n=20 Participants
|
1 Participants
n=25 Participants
|
5 Participants
n=21 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
8 Participants
n=113 Participants
|
|
Highest Parental Education
Less than Bachelor's
|
6 Participants
n=22 Participants
|
7 Participants
n=20 Participants
|
6 Participants
n=25 Participants
|
6 Participants
n=21 Participants
|
2 Participants
n=19 Participants
|
1 Participants
n=6 Participants
|
28 Participants
n=113 Participants
|
|
Highest Parental Education
Bachelor's
|
10 Participants
n=22 Participants
|
6 Participants
n=20 Participants
|
11 Participants
n=25 Participants
|
10 Participants
n=21 Participants
|
8 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
48 Participants
n=113 Participants
|
|
Highest Parental Education
Advanced Degree
|
6 Participants
n=22 Participants
|
7 Participants
n=20 Participants
|
8 Participants
n=25 Participants
|
5 Participants
n=21 Participants
|
9 Participants
n=19 Participants
|
2 Participants
n=6 Participants
|
37 Participants
n=113 Participants
|
|
Health Insurance
Private
|
16 Participants
n=22 Participants
|
19 Participants
n=20 Participants
|
22 Participants
n=25 Participants
|
18 Participants
n=21 Participants
|
14 Participants
n=19 Participants
|
3 Participants
n=6 Participants
|
92 Participants
n=113 Participants
|
|
Health Insurance
Public
|
4 Participants
n=22 Participants
|
1 Participants
n=20 Participants
|
3 Participants
n=25 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=19 Participants
|
2 Participants
n=6 Participants
|
18 Participants
n=113 Participants
|
|
Health Insurance
None
|
2 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
2 Participants
n=113 Participants
|
|
Health Insurance
Missing
|
0 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=19 Participants
|
1 Participants
n=6 Participants
|
1 Participants
n=113 Participants
|
|
BMI Percentile at Randomization
|
78 Percentile
n=22 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
53 Percentile
n=20 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
58 Percentile
n=25 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
65 Percentile
n=20 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
43 Percentile
n=19 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
32 Percentile
n=6 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
56 Percentile
n=112 Participants • 1 participant in the Non-HCL placebo group was missing BMI percentile at randomization.
|
|
Time Since Diagnosis at Randomization (days)
|
24 Days
STANDARD_DEVIATION 5 • n=22 Participants
|
24 Days
STANDARD_DEVIATION 5 • n=20 Participants
|
24 Days
STANDARD_DEVIATION 5 • n=25 Participants
|
25 Days
STANDARD_DEVIATION 4 • n=21 Participants
|
23 Days
STANDARD_DEVIATION 5 • n=19 Participants
|
23 Days
STANDARD_DEVIATION 5 • n=6 Participants
|
24 Days
STANDARD_DEVIATION 5 • n=113 Participants
|
|
Lab HbA1c at Randomization (%)
|
10.1 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.6 • n=22 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
10.3 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.1 • n=19 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
10.6 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.7 • n=25 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
10.1 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.4 • n=20 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
10.6 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.2 • n=19 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
9.4 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.5 • n=6 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
10.6 Percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.7 • n=111 Participants • 1 participant randomized to HCL + Placebo and 1 participant randomized to Non-HCL + Placebo were missing HbA1c at randomization.
|
|
Systolic Blood Pressure at Randomization (mmHg)
|
108 mmHg
STANDARD_DEVIATION 11 • n=22 Participants
|
107 mmHg
STANDARD_DEVIATION 9 • n=20 Participants
|
111 mmHg
STANDARD_DEVIATION 7 • n=25 Participants
|
108 mmHg
STANDARD_DEVIATION 9 • n=21 Participants
|
103 mmHg
STANDARD_DEVIATION 8 • n=19 Participants
|
95 mmHg
STANDARD_DEVIATION 9 • n=6 Participants
|
107 mmHg
STANDARD_DEVIATION 10 • n=113 Participants
|
|
Diastolic Blood Pressure at Randomization (mmHg)
|
62 mmHg
STANDARD_DEVIATION 7 • n=22 Participants
|
62 mmHg
STANDARD_DEVIATION 6 • n=20 Participants
|
65 mmHg
STANDARD_DEVIATION 8 • n=25 Participants
|
65 mmHg
STANDARD_DEVIATION 8 • n=21 Participants
|
62 mmHg
STANDARD_DEVIATION 8 • n=19 Participants
|
63 mmHg
STANDARD_DEVIATION 7 • n=6 Participants
|
63 mmHg
STANDARD_DEVIATION 7 • n=113 Participants
|
|
DKA at Diagnosis
Yes
|
8 Participants
n=22 Participants
|
7 Participants
n=20 Participants
|
10 Participants
n=25 Participants
|
11 Participants
n=21 Participants
|
11 Participants
n=19 Participants
|
4 Participants
n=6 Participants
|
51 Participants
n=113 Participants
|
|
DKA at Diagnosis
No
|
13 Participants
n=22 Participants
|
13 Participants
n=20 Participants
|
15 Participants
n=25 Participants
|
10 Participants
n=21 Participants
|
7 Participants
n=19 Participants
|
2 Participants
n=6 Participants
|
60 Participants
n=113 Participants
|
|
DKA at Diagnosis
Missing
|
1 Participants
n=22 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=19 Participants
|
0 Participants
n=6 Participants
|
2 Participants
n=113 Participants
|
|
Tanner Staging
Group 1
|
6 Participants
n=22 Participants
|
8 Participants
n=20 Participants
|
3 Participants
n=25 Participants
|
4 Participants
n=21 Participants
|
18 Participants
n=19 Participants
|
5 Participants
n=6 Participants
|
44 Participants
n=113 Participants
|
|
Tanner Staging
Group 2-5
|
16 Participants
n=22 Participants
|
12 Participants
n=20 Participants
|
22 Participants
n=25 Participants
|
17 Participants
n=21 Participants
|
1 Participants
n=19 Participants
|
1 Participants
n=6 Participants
|
69 Participants
n=113 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
C-peptide Area Under the Curve (AUC)
Randomization
|
0.57 (pmol/ml)*minutes
Standard Deviation 0.22
|
0.60 (pmol/ml)*minutes
Standard Deviation 0.18
|
0.66 (pmol/ml)*minutes
Standard Deviation 0.20
|
0.60 (pmol/ml)*minutes
Standard Deviation 0.22
|
|
C-peptide Area Under the Curve (AUC)
52 Weeks
|
0.45 (pmol/ml)*minutes
Standard Deviation 0.30
|
0.50 (pmol/ml)*minutes
Standard Deviation 0.31
|
0.65 (pmol/ml)*minutes
Standard Deviation 0.31
|
0.44 (pmol/ml)*minutes
Standard Deviation 0.30
|
SECONDARY outcome
Timeframe: 13, 26 and 39 weeksPopulation: 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.
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.
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
C-peptide AUC
Randomization
|
0.57 (pmol/ml)*minutes
Standard Deviation 0.22
|
0.60 (pmol/ml)*minutes
Standard Deviation 0.18
|
0.66 (pmol/ml)*minutes
Standard Deviation 0.20
|
0.60 (pmol/ml)*minutes
Standard Deviation 0.22
|
|
C-peptide AUC
Week 13
|
0.63 (pmol/ml)*minutes
Standard Deviation 0.23
|
0.69 (pmol/ml)*minutes
Standard Deviation 0.25
|
0.75 (pmol/ml)*minutes
Standard Deviation 0.26
|
0.69 (pmol/ml)*minutes
Standard Deviation 0.23
|
|
C-peptide AUC
Week 26
|
0.62 (pmol/ml)*minutes
Standard Deviation 0.28
|
0.63 (pmol/ml)*minutes
Standard Deviation 0.28
|
0.77 (pmol/ml)*minutes
Standard Deviation 0.30
|
0.62 (pmol/ml)*minutes
Standard Deviation 0.25
|
|
C-peptide AUC
Week 39
|
0.51 (pmol/ml)*minutes
Standard Deviation 0.30
|
0.57 (pmol/ml)*minutes
Standard Deviation 0.30
|
0.71 (pmol/ml)*minutes
Standard Deviation 0.31
|
0.52 (pmol/ml)*minutes
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: 13, 26, 39 weeks and 52 weeksPopulation: 1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was excluded from the analyses.
Maximum of all C-peptide values during the MMTT
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Peak C-peptide
Randomization
|
0.72 pmol/mL
Standard Deviation 0.25
|
0.78 pmol/mL
Standard Deviation 0.23
|
0.96 pmol/mL
Standard Deviation 0.30
|
0.89 pmol/mL
Standard Deviation 0.27
|
|
Peak C-peptide
13 Weeks
|
0.81 pmol/mL
Standard Deviation 0.27
|
0.87 pmol/mL
Standard Deviation 0.29
|
0.84 pmol/mL
Standard Deviation 0.24
|
0.78 pmol/mL
Standard Deviation 0.27
|
|
Peak C-peptide
26 Weeks
|
0.78 pmol/mL
Standard Deviation 0.34
|
0.76 pmol/mL
Standard Deviation 0.33
|
0.97 pmol/mL
Standard Deviation 0.35
|
0.76 pmol/mL
Standard Deviation 0.30
|
|
Peak C-peptide
39 Weeks
|
0.65 pmol/mL
Standard Deviation 0.35
|
0.69 pmol/mL
Standard Deviation 0.35
|
0.89 pmol/mL
Standard Deviation 0.36
|
0.63 pmol/mL
Standard Deviation 0.32
|
|
Peak C-peptide
52 Weeks
|
0.56 pmol/mL
Standard Deviation 0.36
|
0.62 pmol/mL
Standard Deviation 0.37
|
0.83 pmol/mL
Standard Deviation 0.37
|
0.55 pmol/mL
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: 13, 26, 39 weeks and 52 weeksPopulation: 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).
Percentage where maximum of all C-peptide values during the MMTT \>= 0.2 pmol/ml
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
Randomization
|
60 Participants
|
51 Participants
|
46 Participants
|
40 Participants
|
|
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
13 Weeks
|
58 Participants
|
50 Participants
|
45 Participants
|
39 Participants
|
|
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
26 Weeks
|
56 Participants
|
47 Participants
|
44 Participants
|
37 Participants
|
|
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
39 Weeks
|
49 Participants
|
38 Participants
|
41 Participants
|
31 Participants
|
|
Number of Participants With a Peak C-peptide >= 0.2 Pmol/ml
52 Weeks
|
45 Participants
|
36 Participants
|
41 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
Mean glucose between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
CGM Mean Glucose
6 Weeks
|
129 mg/dL
Standard Deviation 12
|
139 mg/dL
Standard Deviation 29
|
131 mg/dL
Standard Deviation 23
|
132 mg/dL
Standard Deviation 22
|
|
CGM Mean Glucose
13 Weeks
|
132 mg/dL
Standard Deviation 15
|
140 mg/dL
Standard Deviation 26
|
134 mg/dL
Standard Deviation 22
|
134 mg/dL
Standard Deviation 22
|
|
CGM Mean Glucose
26 Weeks
|
135 mg/dL
Standard Deviation 17
|
152 mg/dL
Standard Deviation 35
|
138 mg/dL
Standard Deviation 32
|
144 mg/dL
Standard Deviation 27
|
|
CGM Mean Glucose
39 Weeks
|
140 mg/dL
Standard Deviation 19
|
161 mg/dL
Standard Deviation 36
|
141 mg/dL
Standard Deviation 23
|
155 mg/dL
Standard Deviation 38
|
|
CGM Mean Glucose
52 Weeks
|
145 mg/dL
Standard Deviation 19
|
167 mg/dL
Standard Deviation 42
|
151 mg/dL
Standard Deviation 27
|
159 mg/dL
Standard Deviation 41
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
CGM sensor glucose values from 70 to 180 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time in Range (70-180 mg/dL)
6 Weeks
|
86 Percent of Time
Standard Deviation 8
|
84 Percent of Time
Standard Deviation 9
|
85 Percent of Time
Standard Deviation 15
|
84 Percent of Time
Standard Deviation 13
|
|
Percentage of CGM Time in Range (70-180 mg/dL)
13 Weeks
|
84 Percent of Time
Standard Deviation 9
|
79 Percent of Time
Standard Deviation 16
|
83 Percent of Time
Standard Deviation 15
|
84 Percent of Time
Standard Deviation 13
|
|
Percentage of CGM Time in Range (70-180 mg/dL)
26 Weeks
|
83 Percent of Time
Standard Deviation 10
|
73 Percent of Time
Standard Deviation 20
|
81 Percent of Time
Standard Deviation 17
|
78 Percent of Time
Standard Deviation 17
|
|
Percentage of CGM Time in Range (70-180 mg/dL)
39 Weeks
|
80 Percent of Time
Standard Deviation 11
|
68 Percent of Time
Standard Deviation 21
|
80 Percent of Time
Standard Deviation 15
|
72 Percent of Time
Standard Deviation 20
|
|
Percentage of CGM Time in Range (70-180 mg/dL)
52 Weeks
|
78 Percent of Time
Standard Deviation 11
|
64 Percent of Time
Standard Deviation 22
|
74 Percent of Time
Standard Deviation 18
|
70 Percent of Time
Standard Deviation 21
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in the Non-HCL+Placebo group dropped at the randomization visit and was not analyzed.
Percentage of CGM sensor glucose values from 70 to 140 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time in Range 70-140 mg/dL
6 Weeks
|
69 Percentage of Time
Standard Deviation 11
|
60 Percentage of Time
Standard Deviation 22
|
67 Percentage of Time
Standard Deviation 19
|
66 Percentage of Time
Standard Deviation 18
|
|
Percentage of CGM Time in Range 70-140 mg/dL
13 Weeks
|
67 Percentage of Time
Standard Deviation 13
|
59 Percentage of Time
Standard Deviation 22
|
65 Percentage of Time
Standard Deviation 19
|
65 Percentage of Time
Standard Deviation 19
|
|
Percentage of CGM Time in Range 70-140 mg/dL
26 Weeks
|
64 Percentage of Time
Standard Deviation 13
|
51 Percentage of Time
Standard Deviation 21
|
61 Percentage of Time
Standard Deviation 20
|
57 Percentage of Time
Standard Deviation 19
|
|
Percentage of CGM Time in Range 70-140 mg/dL
39 Weeks
|
60 Percentage of Time
Standard Deviation 14
|
46 Percentage of Time
Standard Deviation 21
|
58 Percentage of Time
Standard Deviation 19
|
51 Percentage of Time
Standard Deviation 20
|
|
Percentage of CGM Time in Range 70-140 mg/dL
52 Weeks
|
56 Percentage of Time
Standard Deviation 13
|
43 Percentage of Time
Standard Deviation 21
|
51 Percentage of Time
Standard Deviation 19
|
49 Percentage of Time
Standard Deviation 21
|
SECONDARY outcome
Timeframe: 52 WeeksPopulation: 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).
Percentage of patients with \>=70% sensor glucose values from 70 to 180 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=59 Participants
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
|
Non-HCL and Standard Care
n=47 Participants
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
|
Verapamil
n=44 Participants
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
|
Placebo
n=37 Participants
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
|
|---|---|---|---|---|
|
Number of Participants With CGM Time in Range 70-180 mg/dL >=70% at 52 Weeks
|
46 Participants
|
22 Participants
|
30 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
CGM sensor glucose values \>140 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time >140 mg/dL
6 Weeks
|
29 Percent of Time
Standard Deviation 11
|
38 Percent of Time
Standard Deviation 23
|
32 Percent of Time
Standard Deviation 19
|
32 Percent of Time
Standard Deviation 18
|
|
Percentage of CGM Time >140 mg/dL
13 Weeks
|
32 Percent of Time
Standard Deviation 13
|
40 Percent of Time
Standard Deviation 22
|
34 Percent of Time
Standard Deviation 19
|
33 Percent of Time
Standard Deviation 20
|
|
Percentage of CGM Time >140 mg/dL
26 Weeks
|
34 Percent of Time
Standard Deviation 13
|
47 Percent of Time
Standard Deviation 22
|
36 Percent of Time
Standard Deviation 20
|
41 Percent of Time
Standard Deviation 20
|
|
Percentage of CGM Time >140 mg/dL
39 Weeks
|
38 Percent of Time
Standard Deviation 14
|
53 Percent of Time
Standard Deviation 21
|
40 Percent of Time
Standard Deviation 19
|
47 Percent of Time
Standard Deviation 21
|
|
Percentage of CGM Time >140 mg/dL
52 Weeks
|
42 Percent of Time
Standard Deviation 14
|
56 Percent of Time
Standard Deviation 22
|
47 Percent of Time
Standard Deviation 19
|
49 Percent of Time
Standard Deviation 22
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
CGM sensor glucose values \>180 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time >180 mg/dL
6 Weeks
|
12 Percent of Time
Standard Deviation 8
|
19 Percent of Time
Standard Deviation 19
|
13 Percent of Time
Standard Deviation 15
|
14 Percent of Time
Standard Deviation 14
|
|
Percentage of CGM Time >180 mg/dL
13 Weeks
|
14 Percent of Time
Standard Deviation 9
|
19 Percent of Time
Standard Deviation 17
|
15 Percent of Time
Standard Deviation 15
|
15 Percent of Time
Standard Deviation 14
|
|
Percentage of CGM Time >180 mg/dL
26 Weeks
|
15 Percent of Time
Standard Deviation 10
|
25 Percent of Time
Standard Deviation 20
|
17 Percent of Time
Standard Deviation 17
|
21 Percent of Time
Standard Deviation 18
|
|
Percentage of CGM Time >180 mg/dL
39 Weeks
|
18 Percent of Time
Standard Deviation 11
|
30 Percent of Time
Standard Deviation 21
|
19 Percent of Time
Standard Deviation 15
|
26 Percent of Time
Standard Deviation 21
|
|
Percentage of CGM Time >180 mg/dL
52 Weeks
|
20 Percent of Time
Standard Deviation 11
|
34 Percent of Time
Standard Deviation 22
|
25 Percent of Time
Standard Deviation 18
|
28 Percent of Time
Standard Deviation 21
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Percentage of CGM sensor glucose values \>250 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time >250 mg/dL
6 Weeks
|
1 Percent of Time
Standard Deviation 2
|
3 Percent of Time
Standard Deviation 4
|
1 Percent of Time
Standard Deviation 1
|
2 Percent of Time
Standard Deviation 3
|
|
Percentage of CGM Time >250 mg/dL
13 Weeks
|
2 Percent of Time
Standard Deviation 3
|
3 Percent of Time
Standard Deviation 4
|
2 Percent of Time
Standard Deviation 2
|
2 Percent of Time
Standard Deviation 3
|
|
Percentage of CGM Time >250 mg/dL
26 Weeks
|
2 Percent of Time
Standard Deviation 3
|
6 Percent of Time
Standard Deviation 8
|
2 Percent of Time
Standard Deviation 3
|
4 Percent of Time
Standard Deviation 6
|
|
Percentage of CGM Time >250 mg/dL
39 Weeks
|
3 Percent of Time
Standard Deviation 3
|
9 Percent of Time
Standard Deviation 12
|
3 Percent of Time
Standard Deviation 4
|
7 Percent of Time
Standard Deviation 9
|
|
Percentage of CGM Time >250 mg/dL
52 Weeks
|
4 Percent of Time
Standard Deviation 4
|
10 Percent of Time
Standard Deviation 13
|
5 Percent of Time
Standard Deviation 6
|
8 Percent of Time
Standard Deviation 10
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Percentage of CGM sensor glucose values \<54 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time <54 mg/dL
6 Weeks
|
0.22 Percent of Time
Standard Error 0.22
|
0.11 Percent of Time
Standard Error 0.13
|
0.14 Percent of Time
Standard Error 0.16
|
0.16 Percent of Time
Standard Error 0.16
|
|
Percentage of CGM Time <54 mg/dL
13 Weeks
|
0.23 Percent of Time
Standard Error 0.21
|
0.12 Percent of Time
Standard Error 0.16
|
0.19 Percent of Time
Standard Error 0.20
|
0.16 Percent of Time
Standard Error 0.19
|
|
Percentage of CGM Time <54 mg/dL
26 Weeks
|
0.25 Percent of Time
Standard Error 0.25
|
0.10 Percent of Time
Standard Error 0.11
|
0.22 Percent of Time
Standard Error 0.25
|
0.14 Percent of Time
Standard Error 0.18
|
|
Percentage of CGM Time <54 mg/dL
39 Weeks
|
0.32 Percent of Time
Standard Error 0.34
|
0.16 Percent of Time
Standard Error 0.20
|
0.21 Percent of Time
Standard Error 0.27
|
0.26 Percent of Time
Standard Error 0.27
|
|
Percentage of CGM Time <54 mg/dL
52 Weeks
|
0.29 Percent of Time
Standard Error 0.34
|
0.18 Percent of Time
Standard Error 0.21
|
0.20 Percent of Time
Standard Error 0.24
|
0.24 Percent of Time
Standard Error 0.26
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Percentage of CGM sensor glucose values \<70 mg/dL between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Percentage of CGM Time <70 mg/dL
6 Weeks
|
1.7 Percent of Time
Standard Deviation 1.0
|
1.5 Percent of Time
Standard Deviation 1.6
|
1.5 Percent of Time
Standard Deviation 1.5
|
1.7 Percent of Time
Standard Deviation 1.6
|
|
Percentage of CGM Time <70 mg/dL
13 Weeks
|
1.6 Percent of Time
Standard Deviation 1.2
|
1.2 Percent of Time
Standard Deviation 1.1
|
1.4 Percent of Time
Standard Deviation 0.9
|
1.4 Percent of Time
Standard Deviation 1.5
|
|
Percentage of CGM Time <70 mg/dL
26 Weeks
|
1.9 Percent of Time
Standard Deviation 1.1
|
1.2 Percent of Time
Standard Deviation 1.0
|
1.6 Percent of Time
Standard Deviation 1.4
|
1.4 Percent of Time
Standard Deviation 1.2
|
|
Percentage of CGM Time <70 mg/dL
39 Weeks
|
2.0 Percent of Time
Standard Deviation 1.3
|
1.2 Percent of Time
Standard Deviation 1.3
|
1.5 Percent of Time
Standard Deviation 1.4
|
1.7 Percent of Time
Standard Deviation 1.6
|
|
Percentage of CGM Time <70 mg/dL
52 Weeks
|
1.8 Percent of Time
Standard Deviation 1.2
|
1.4 Percent of Time
Standard Deviation 1.4
|
1.3 Percent of Time
Standard Deviation 1.2
|
1.6 Percent of Time
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Coefficient of variation between treatment groups. Calculated as the standard deviation of CGM glucose values divided by the mean of CGM glucose values.
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
CGM Coefficient of Variation
6 Weeks
|
31 Coefficient of Variation Percentage
Standard Deviation 5
|
30 Coefficient of Variation Percentage
Standard Deviation 6
|
28 Coefficient of Variation Percentage
Standard Deviation 5
|
30 Coefficient of Variation Percentage
Standard Deviation 6
|
|
CGM Coefficient of Variation
13 Weeks
|
31 Coefficient of Variation Percentage
Standard Deviation 6
|
30 Coefficient of Variation Percentage
Standard Deviation 7
|
29 Coefficient of Variation Percentage
Standard Deviation 6
|
29 Coefficient of Variation Percentage
Standard Deviation 6
|
|
CGM Coefficient of Variation
26 Weeks
|
32 Coefficient of Variation Percentage
Standard Deviation 5
|
32 Coefficient of Variation Percentage
Standard Deviation 6
|
30 Coefficient of Variation Percentage
Standard Deviation 6
|
31 Coefficient of Variation Percentage
Standard Deviation 5
|
|
CGM Coefficient of Variation
39 Weeks
|
34 Coefficient of Variation Percentage
Standard Deviation 6
|
33 Coefficient of Variation Percentage
Standard Deviation 6
|
31 Coefficient of Variation Percentage
Standard Deviation 6
|
33 Coefficient of Variation Percentage
Standard Deviation 5
|
|
CGM Coefficient of Variation
52 Weeks
|
34 Coefficient of Variation Percentage
Standard Deviation 6
|
33 Coefficient of Variation Percentage
Standard Deviation 5
|
32 Coefficient of Variation Percentage
Standard Deviation 6
|
33 Coefficient of Variation Percentage
Standard Deviation 5
|
SECONDARY outcome
Timeframe: 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
HbA1c between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
HbA1c
Randomization
|
10.3 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.3
|
10.2 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.6
|
10.3 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.7
|
10.2 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.2
|
|
HbA1c
13 Weeks
|
6.4 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.5
|
6.5 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.9
|
6.3 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.8
|
6.4 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.6
|
|
HbA1c
26 Weeks
|
6.4 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.6
|
6.6 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.0
|
6.3 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.9
|
6.5 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.8
|
|
HbA1c
39 Weeks
|
6.6 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.7
|
7.0 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.2
|
6.4 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.9
|
7.0 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.1
|
|
HbA1c
52 Weeks
|
6.5 Percentage of Glycosylated Hemoglobin
Standard Deviation 0.7
|
7.1 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.3
|
6.6 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.0
|
6.9 Percentage of Glycosylated Hemoglobin
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: 13, 26, 39 weeks and 52 weeksPopulation: 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).
Percentage of participants with HbA1c \< 7.0% between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Number of Participants With HbA1c <7.0%
Randomization
|
2 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With HbA1c <7.0%
13 Weeks
|
48 Participants
|
36 Participants
|
38 Participants
|
32 Participants
|
|
Number of Participants With HbA1c <7.0%
26 Weeks
|
45 Participants
|
31 Participants
|
37 Participants
|
25 Participants
|
|
Number of Participants With HbA1c <7.0%
39 Weeks
|
44 Participants
|
23 Participants
|
33 Participants
|
22 Participants
|
|
Number of Participants With HbA1c <7.0%
52 Weeks
|
42 Participants
|
26 Participants
|
32 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: 13, 26, 39 weeks and 52 weeksPopulation: 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).
Percentage of participants with HbA1c \< 6.5% between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Number of Participants With HbA1c <6.5%
Randomization
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With HbA1c <6.5%
13 Weeks
|
27 Participants
|
24 Participants
|
27 Participants
|
20 Participants
|
|
Number of Participants With HbA1c <6.5%
26 Weeks
|
37 Participants
|
23 Participants
|
31 Participants
|
22 Participants
|
|
Number of Participants With HbA1c <6.5%
39 Weeks
|
33 Participants
|
20 Participants
|
30 Participants
|
18 Participants
|
|
Number of Participants With HbA1c <6.5%
52 Weeks
|
28 Participants
|
19 Participants
|
25 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Total daily insulin per kg between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Total Daily Insulin Per kg
Randomization
|
0.68 U/kg/day
Standard Deviation 0.28
|
0.66 U/kg/day
Standard Deviation 0.30
|
0.74 U/kg/day
Standard Deviation 0.29
|
0.64 U/kg/day
Standard Deviation 0.27
|
|
Total Daily Insulin Per kg
6 Weeks
|
0.54 U/kg/day
Standard Deviation 0.26
|
0.55 U/kg/day
Standard Deviation 0.33
|
0.55 U/kg/day
Standard Deviation 0.33
|
0.54 U/kg/day
Standard Deviation 0.28
|
|
Total Daily Insulin Per kg
13 Weeks
|
0.51 U/kg/day
Standard Deviation 0.23
|
0.53 U/kg/day
Standard Deviation 0.25
|
0.54 U/kg/day
Standard Deviation 0.25
|
0.54 U/kg/day
Standard Deviation 0.26
|
|
Total Daily Insulin Per kg
26 Weeks
|
0.61 U/kg/day
Standard Deviation 0.28
|
0.53 U/kg/day
Standard Deviation 0.23
|
0.57 U/kg/day
Standard Deviation 0.28
|
0.58 U/kg/day
Standard Deviation 0.29
|
|
Total Daily Insulin Per kg
39 Weeks
|
0.68 U/kg/day
Standard Deviation 0.32
|
0.58 U/kg/day
Standard Deviation 0.27
|
0.59 U/kg/day
Standard Deviation 0.29
|
0.66 U/kg/day
Standard Deviation 0.32
|
|
Total Daily Insulin Per kg
52 Weeks
|
0.74 U/kg/day
Standard Deviation 0.32
|
0.64 U/kg/day
Standard Deviation 0.25
|
0.65 U/kg/day
Standard Deviation 0.26
|
0.74 U/kg/day
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: 6, 13, 26, 39 weeks and 52 weeksPopulation: 1 participant in Non-HCL+Placebo group dropped at baseline and was not analyzed.
Ratio of basal:bolus insulin between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|---|---|
|
Basal:Bolus Ratio
13 Weeks
|
0.61 Daily Basal/Bolus Ratio
|
1 Daily Basal/Bolus Ratio
|
0.89 Daily Basal/Bolus Ratio
|
0.82 Daily Basal/Bolus Ratio
|
|
Basal:Bolus Ratio
Randomization
|
0.96 Daily Basal/Bolus Ratio
|
1.0 Daily Basal/Bolus Ratio
|
1.1 Daily Basal/Bolus Ratio
|
1.1 Daily Basal/Bolus Ratio
|
|
Basal:Bolus Ratio
6 Weeks
|
0.61 Daily Basal/Bolus Ratio
|
1.1 Daily Basal/Bolus Ratio
|
0.89 Daily Basal/Bolus Ratio
|
0.85 Daily Basal/Bolus Ratio
|
|
Basal:Bolus Ratio
26 Weeks
|
0.59 Daily Basal/Bolus Ratio
|
0.85 Daily Basal/Bolus Ratio
|
0.72 Daily Basal/Bolus Ratio
|
0.75 Daily Basal/Bolus Ratio
|
|
Basal:Bolus Ratio
39 Weeks
|
0.67 Daily Basal/Bolus Ratio
|
0.72 Daily Basal/Bolus Ratio
|
0.75 Daily Basal/Bolus Ratio
|
0.72 Daily Basal/Bolus Ratio
|
|
Basal:Bolus Ratio
52 Weeks
|
0.69 Daily Basal/Bolus Ratio
|
0.75 Daily Basal/Bolus Ratio
|
0.82 Daily Basal/Bolus Ratio
|
0.72 Daily Basal/Bolus Ratio
|
SECONDARY outcome
Timeframe: 52 weeksFrequency of episodes of severe hypoglycemia between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=41 Participants
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
|
|---|---|---|---|---|
|
Severe Hypoglycemia
|
1 Number of Severe Hypoglycemic Events
|
1 Number of Severe Hypoglycemic Events
|
1 Number of Severe Hypoglycemic Events
|
1 Number of Severe Hypoglycemic Events
|
SECONDARY outcome
Timeframe: 52 weeksFrequency of episodes of DKA between treatment groups
Outcome measures
| Measure |
HCL and Intensive Management
n=61 Participants
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
|
Non-HCL and Standard Care
n=51 Participants
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
|
Verapamil
n=47 Participants
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
|
Placebo
n=41 Participants
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
|
|---|---|---|---|---|
|
DKA
|
1 Number of DKA Events
|
1 Number of DKA Events
|
0 Number of DKA Events
|
1 Number of DKA Events
|
Adverse Events
HCL and Verapamil
Serious events: 3 serious events
Other events: 20 other events
Deaths: 0 deaths
HCL and Placebo
Serious events: 1 serious events
Other events: 16 other events
Deaths: 0 deaths
Non-HCL and Verapamil
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Non-HCL and Placebo
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
HCL Only
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Non-HCL Only
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HCL and Verapamil
n=22 participants at risk
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
|
HCL and Placebo
n=20 participants at risk
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
|
Non-HCL and Verapamil
n=25 participants at risk
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
|
Non-HCL and Placebo
n=21 participants at risk
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
|
HCL Only
n=19 participants at risk
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
|
Non-HCL Only
n=6 participants at risk
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
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
Suicidal Ideation
|
9.1%
2/22 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Psychiatric disorders
Depression
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Endocrine disorders
Hypoglycemia
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Endocrine disorders
Diabetic Ketoacidosis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Metabolism and nutrition disorders
Ketosis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
Other adverse events
| Measure |
HCL and Verapamil
n=22 participants at risk
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
|
HCL and Placebo
n=20 participants at risk
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
|
Non-HCL and Verapamil
n=25 participants at risk
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
|
Non-HCL and Placebo
n=21 participants at risk
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
|
HCL Only
n=19 participants at risk
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
|
Non-HCL Only
n=6 participants at risk
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
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Cardiac Arrhythmia
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Cardiac disorders
1st Degree Heart Block
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Cardiac disorders
Premature Ventricular Contractions
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Ear and labyrinth disorders
Ear Infection
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Blood and lymphatic system disorders
Swollen Glands
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Cardiac disorders
2nd Degree Heart Block
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Ear and labyrinth disorders
Otitis Externa
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
Ear and labyrinth disorders
Otitis Media Acute
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Ear and labyrinth disorders
Pain in Ear
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Endocrine disorders
Hyperglycemia
|
13.6%
3/22 • Number of events 6 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Endocrine disorders
Thyroiditis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
10.0%
2/20 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
9.5%
2/21 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Acid Indegestion
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Bloody Stool
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Celiac Disease
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
15.8%
3/19 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Constipation
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Diarrhea
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Gastroenteritis
|
9.1%
2/22 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Hyperemesis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Stomach Pain
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Stomach Virus
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Tooth Infection
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Upset Stomach
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
2/22 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Catheter Site Pain
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Chest Pain
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Fatigue
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Fever
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
9.5%
2/21 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
26.3%
5/19 • Number of events 6 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Malaise
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Pain NOS
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
General disorders
Swelling of Feet
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Immune system disorders
Allergy NOS
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Immune system disorders
Hives
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Immune system disorders
Seasonal Allergy
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Immune system disorders
Vitiligo
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Infections and infestations
Covid-19
|
13.6%
3/22 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
20.0%
4/20 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
24.0%
6/25 • Number of events 7 • Adverse event data where collected during the 52 week RCT phase.
|
14.3%
3/21 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
15.8%
3/19 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Infections and infestations
Influenza
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Infections and infestations
Tinea Pedis
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Infections and infestations
Viral Syndrome
|
9.1%
2/22 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Injury, poisoning and procedural complications
Animal Bite
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Injury, poisoning and procedural complications
Foot Injury
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Injury, poisoning and procedural complications
Motor Vehicle Accident
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
10.0%
2/20 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Investigations
Elevated Liver Enzymes
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Investigations
Heart Murmur
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Metabolism and nutrition disorders
Abnormal Weight Gain
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Metabolism and nutrition disorders
Ketosis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Arm Fracture
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Foot Pain
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Leg Cramps
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Leg Pain
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramps
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Pain in Elbow
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Sprained Ankle
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular Joint Disorder
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Musculoskeletal and connective tissue disorders
Wrist Fracture
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Autism
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Headache
|
13.6%
3/22 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
15.0%
3/20 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
19.0%
4/21 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
15.8%
3/19 • Number of events 7 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Numbness in Feet
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Paresthesia
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Pre-syncope
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Tingling Sensation
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Vasovagal Attack
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Psychiatric disorders
Adjustment Disorder
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Psychiatric disorders
Depression
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Psychiatric disorders
Panic Attack
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Renal and urinary disorders
Urinary Tract Infection
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
12.0%
3/25 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Cold
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
12.0%
3/25 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
14.3%
3/21 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
15.8%
3/19 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
33.3%
2/6 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
26.3%
5/19 • Number of events 6 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal Drip
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Infection
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Runny Nose
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Infection
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
9.1%
2/22 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
8.0%
2/25 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
9.5%
2/21 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Streptococcal Sore Throat
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
13.6%
3/22 • Number of events 3 • Adverse event data where collected during the 52 week RCT phase.
|
25.0%
5/20 • Number of events 5 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
16.7%
1/6 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Acne
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
4.8%
1/21 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Bruise
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Contact Dermatitis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Ingrown toe nail
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Lipohypertrophy
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
19.0%
4/21 • Number of events 4 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Skin Abrasion
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Skin Bacterial Infection
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Skin Disorder NOS
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Skin Infection
|
4.5%
1/22 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
10.5%
2/19 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Skin and subcutaneous tissue disorders
Tinea Corporis
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Surgical and medical procedures
Tooth Extraction
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
5.3%
1/19 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Vascular disorders
Benign Essential Hypertension
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
4.0%
1/25 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Vascular disorders
Hypotension
|
4.5%
1/22 • Number of events 2 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/20 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
|
Nervous system disorders
Syncope
|
0.00%
0/22 • Adverse event data where collected during the 52 week RCT phase.
|
5.0%
1/20 • Number of events 1 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/25 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/21 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/19 • Adverse event data where collected during the 52 week RCT phase.
|
0.00%
0/6 • Adverse event data where collected during the 52 week RCT phase.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place