Trial Outcomes & Findings for Study of Human Regular U-500 Insulin in Adult Participants With Type 2 Diabetes (NCT NCT01774968)
NCT ID: NCT01774968
Last Updated: 2015-09-22
Results Overview
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
325 participants
Primary outcome timeframe
Baseline, Week 24
Results posted on
2015-09-22
Participant Flow
Participant milestones
| Measure |
Human Regular U-500 Insulin TID
Human Regular U-500 Insulin (U-500R) titrated based on blood glucose readings, administered subcutaneously (SC), three times a day (TID) for 24 weeks.
|
Human Regular U-500 Insulin BID
U-500R Insulin titrated based on blood glucose readings, administered SC, two times a day (BID) for 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
162
|
163
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
162
|
161
|
|
Overall Study
COMPLETED
|
132
|
128
|
|
Overall Study
NOT COMPLETED
|
30
|
35
|
Reasons for withdrawal
| Measure |
Human Regular U-500 Insulin TID
Human Regular U-500 Insulin (U-500R) titrated based on blood glucose readings, administered subcutaneously (SC), three times a day (TID) for 24 weeks.
|
Human Regular U-500 Insulin BID
U-500R Insulin titrated based on blood glucose readings, administered SC, two times a day (BID) for 24 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
4
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Physician Decision
|
5
|
1
|
|
Overall Study
Protocol Violation
|
14
|
13
|
|
Overall Study
Sponsor Decision
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
6
|
11
|
Baseline Characteristics
Study of Human Regular U-500 Insulin in Adult Participants With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=163 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
Total
n=325 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.31 years
STANDARD_DEVIATION 10.51 • n=5 Participants
|
55.50 years
STANDARD_DEVIATION 9.03 • n=7 Participants
|
55.41 years
STANDARD_DEVIATION 9.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
83 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
172 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
130 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
263 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
133 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
266 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
146 participants
n=5 Participants
|
149 participants
n=7 Participants
|
295 participants
n=5 Participants
|
|
Region of Enrollment
Puerto Rico
|
16 participants
n=5 Participants
|
14 participants
n=7 Participants
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c)
|
-1.12 percentage of HbA1c
Standard Error 0.08
|
-1.22 percentage of HbA1c
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data.
The percentage of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=159 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24
HbA1c ≤6.5% (n=159, 161)
|
20.13 percentage of participants
|
23.60 percentage of participants
|
|
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24
HbA1c <7.0% (n=158, 159)
|
42.41 percentage of participants
|
41.51 percentage of participants
|
|
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24
HbA1c <7.5% (n=148, 143)
|
64.19 percentage of participants
|
61.54 percentage of participants
|
|
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24
HbA1c <8.0% (n=120, 123)
|
77.50 percentage of participants
|
77.24 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through Week 24Population: Randomized participants who received at least 1 dose of U-500R.
Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
30-Day Adjusted Rate of Hypoglycemic Events
Documented Symptomatic HE
|
3.343 events per participant per 30 days
Standard Deviation 3.174
|
3.885 events per participant per 30 days
Standard Deviation 3.448
|
|
30-Day Adjusted Rate of Hypoglycemic Events
Severe HE
|
0.004 events per participant per 30 days
Standard Deviation 0.028
|
0.009 events per participant per 30 days
Standard Deviation 0.053
|
|
30-Day Adjusted Rate of Hypoglycemic Events
Documented Symptomatic Nocturnal HE
|
1.013 events per participant per 30 days
Standard Deviation 1.438
|
1.299 events per participant per 30 days
Standard Deviation 1.540
|
|
30-Day Adjusted Rate of Hypoglycemic Events
Asymptomatic HE
|
1.340 events per participant per 30 days
Standard Deviation 3.215
|
1.028 events per participant per 30 days
Standard Deviation 2.231
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.
LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Body Weight
|
5.44 kilograms (kg)
Standard Error 0.41
|
4.88 kilograms (kg)
Standard Error 0.41
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.
Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin
|
55.19 units
Standard Error 10.16
|
51.39 units
Standard Error 10.24
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.
Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin
|
0.32 units per kilogram (units/kg)
Standard Error 0.08
|
0.32 units per kilogram (units/kg)
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable FPG data.
LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline FPG as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=159 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels
|
-6.66 milligrams per deciliter (mg/dL)
Standard Error 5.64
|
-8.86 milligrams per deciliter (mg/dL)
Standard Error 5.72
|
SECONDARY outcome
Timeframe: Baseline through 6, 12, 18, and 24 weeks.Population: Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data
The cumulative number of participants achieving an HbA1c of ≤6.5%, \<7.0%, \<7.5%, and \<8.0% is summarized at Weeks 6, 12, 18, and 24. The number of participants at risk (n) is also provided for each target value and timepoint.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=154 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=155 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Time to Reach HbA1c Target Values
HbA1c ≤6.5%, Week 12 (n=145, 151)
|
15 participants
|
15 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <8.0%, Week 18 (n=111, 113)
|
85 participants
|
86 participants
|
|
Time to Reach HbA1c Target Values
HbA1c ≤6.5%, Week 6 (n=154, 155)
|
1 participants
|
6 participants
|
|
Time to Reach HbA1c Target Values
HbA1c ≤6.5%, Week 18 (n=140, 145)
|
24 participants
|
27 participants
|
|
Time to Reach HbA1c Target Values
HbA1c ≤6.5%, Week 24 (n=76, 65)
|
28 participants
|
37 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.0%, Week 6 (n=154, 153)
|
14 participants
|
10 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.0%, Week 12 (n=148, 149)
|
31 participants
|
36 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.0%, Week 18 (n=144, 145)
|
52 participants
|
55 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.0%, Week 24 (n=53, 52)
|
60 participants
|
65 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.5%, Week 6 (n=144, 137)
|
30 participants
|
20 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.5%, Week 12 (n=140, 134)
|
59 participants
|
59 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.5%, Week 18 (n=136, 132)
|
81 participants
|
78 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <7.5%, Week 24 (n=34, 31)
|
90 participants
|
87 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <8.0%, Week 6 (n=117, 117)
|
32 participants
|
34 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <8.0%, Week 12 (n=114, 115)
|
66 participants
|
72 participants
|
|
Time to Reach HbA1c Target Values
HbA1c <8.0%, Week 24 (n=20, 19)
|
89 participants
|
95 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 24Population: Randomized participants who received at least 1 dose of U-500R.
Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The percentage of participants with HE at 24 weeks was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Percentage of Participants With Hypoglycemic Events
Documented Symptomatic HE
|
91.98 percentage of participants
|
90.06 percentage of participants
|
|
Percentage of Participants With Hypoglycemic Events
Asymptomatic HE
|
64.20 percentage of participants
|
66.46 percentage of participants
|
|
Percentage of Participants With Hypoglycemic Events
Severe HE
|
1.85 percentage of participants
|
3.73 percentage of participants
|
|
Percentage of Participants With Hypoglycemic Events
Documented Symptomatic Nocturnal HE
|
77.78 percentage of participants
|
80.75 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R. Last observation carried forward (LOCF) was used to impute missing postbaseline values.
The number of insulin injections per day at baseline (Week 0) and at Week 24 are presented.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Number of Insulin Injections
Baseline
|
4.765 injections per day
Standard Deviation 1.234
|
4.783 injections per day
Standard Deviation 1.307
|
|
Change From Baseline to Week 24 in Number of Insulin Injections
Week 24
|
3.000 injections per day
Standard Deviation 0.000
|
2.000 injections per day
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable SMBG data.
The 7-point SMBG is a participant self-administered blood glucose test which utilizes measurements at specific time points over a 24-hour period, including pre-morning meal (fasting), 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and 3 AM. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline SMBG as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=150 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=149 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
2 Hours After Midday Meal (n=143, 133)
|
-24.31 mg/dL
Standard Error 4.50
|
-22.53 mg/dL
Standard Error 4.49
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
2 Hours After Morning Meal (n=146, 133)
|
-21.68 mg/dL
Standard Error 4.29
|
-31.32 mg/dL
Standard Error 4.29
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
Pre-midday Meal (n=150, 149)
|
-23.54 mg/dL
Standard Error 4.17
|
-32.26 mg/dL
Standard Error 4.11
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
Pre-evening Meal (n=150, 149)
|
-34.17 mg/dL
Standard Error 3.93
|
-32.96 mg/dL
Standard Error 3.85
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
2 Hours After Evening Meal (n=147, 142)
|
-40.56 mg/dL
Standard Error 4.13
|
-38.36 mg/dL
Standard Error 4.11
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
3 AM (n=147, 140)
|
-36.77 mg/dL
Standard Error 4.34
|
-47.82 mg/dL
Standard Error 4.29
|
|
Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)
Pre-morning Meal (n=150, 149)
|
-24.10 mg/dL
Standard Error 3.96
|
-29.19 mg/dL
Standard Error 3.91
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Baseline TDD ≤2.0 units/kg (n=50, 46)
|
-0.99 percentage of HbA1c
Standard Error 0.14
|
-1.32 percentage of HbA1c
Standard Error 0.15
|
|
Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Baseline TDD >2.0 units/kg (n=112, 115)
|
-1.19 percentage of HbA1c
Standard Error 0.10
|
-1.18 percentage of HbA1c
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R.
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person \[accompanied by neurologic/cognitive impairment\]), documented symptomatic (DS; an event which is associated with signs/symptoms of hypoglycemia and plasma glucose \[PG\] ≤70 milligrams per deciliter \[mg/dL\]), or nocturnal (Noc; any documented symptomatic HE that occurred between bedtime and waking). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Severe HE, TDD >2 units/kg, Baseline (n=112, 115)
|
0 events per participant per 30 days
Standard Deviation 0
|
0 events per participant per 30 days
Standard Deviation 0
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Severe HE, TDD >2 units/kg, Week 24 (n=112, 115)
|
0.004 events per participant per 30 days
Standard Deviation 0.029
|
0.013 events per participant per 30 days
Standard Deviation 0.062
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
DS HE, TDD ≤2 units/kg, Baseline (n=50, 46)
|
1.958 events per participant per 30 days
Standard Deviation 4.808
|
1.454 events per participant per 30 days
Standard Deviation 3.251
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
DS HE, TDD ≤2 units/kg, Week 24 (n=50, 46))
|
2.356 events per participant per 30 days
Standard Deviation 2.352
|
3.131 events per participant per 30 days
Standard Deviation 3.204
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
DS HE, TDD >2 units/kg, Week 24 (n=112, 115)
|
3.784 events per participant per 30 days
Standard Deviation 3.397
|
4.186 events per participant per 30 days
Standard Deviation 3.509
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Noc. HE, TDD ≤2 units/kg, Baseline (n=50, 46)
|
1.066 events per participant per 30 days
Standard Deviation 2.045
|
0.711 events per participant per 30 days
Standard Deviation 1.965
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Noc. HE, TDD ≤2 units/kg, Week 24 (n=50, 46)
|
1.105 events per participant per 30 days
Standard Deviation 1.153
|
1.282 events per participant per 30 days
Standard Deviation 1.431
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Severe HE, TDD ≤2 units/kg, Baseline (n=50, 46)
|
0 events per participant per 30 days
Standard Deviation 0
|
0 events per participant per 30 days
Standard Deviation 0
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Severe HE, TDD ≤2 units/kg, Week 24 (n=50, 46)
|
0.004 events per participant per 30 days
Standard Deviation 0.025
|
0 events per participant per 30 days
Standard Deviation 0
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
DS HE, TDD >2 units/kg, Baseline (n=112, 115)
|
2.037 events per participant per 30 days
Standard Deviation 4.382
|
1.730 events per participant per 30 days
Standard Deviation 3.180
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Noc. HE, TDD >2 units/kg, Baseline (n=112, 115)
|
0.792 events per participant per 30 days
Standard Deviation 2.465
|
0.585 events per participant per 30 days
Standard Deviation 1.445
|
|
Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg
Noc. HE, TDD >2 units/kg, Week 24 (n=112, 115)
|
1.522 events per participant per 30 days
Standard Deviation 2.018
|
1.753 events per participant per 30 days
Standard Deviation 1.934
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R.
Participants were stratified by their baseline TDD insulin (≤2.0 units (U)/kg or \>2.0 U/kg). The percentage of participants at risk of developing hypoglycemia (including documented symptomatic, asymptomatic, probable symptomatic, unspecified, or severe hypoglycemia) is presented at Baseline and at Week 24 and was calculated using MMRM fit with options of the binomial distribution and log link function including treatment, TDD (\>300 units or ≤300 units), pioglitazone use (yes or no), visit, and treatment-by-visit interaction as fixed effects, and baseline HbA1c value as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD ≤2.0 U/kg, Week 24 risk (n=50, 46)
|
94.00 percentage of participants
|
86.96 percentage of participants
|
|
Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD >2.0 U/kg, Baseline risk (n=112, 115)
|
47.32 percentage of participants
|
51.30 percentage of participants
|
|
Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD >2.0 U/kg, Week 24 risk (n=112, 115)
|
96.43 percentage of participants
|
97.39 percentage of participants
|
|
Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD≤2.0 U/kg, Baseline risk (n=50, 46)
|
56.00 percentage of participants
|
39.13 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.
Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or \>2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or \>8%), baseline TDD (≤300 or \>300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.
Outcome measures
| Measure |
Human Regular U-500 Insulin TID
n=162 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=161 Participants
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD insulin ≤2.0 units/kg (n=50, 46)
|
6.11 kg
Standard Error 0.88
|
6.09 kg
Standard Error 0.93
|
|
Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg
Baseline TDD insulin >2.0 units/kg (n=112, 115)
|
5.08 kg
Standard Error 0.44
|
4.40 kg
Standard Error 0.43
|
Adverse Events
Human Regular U-500 Insulin TID
Serious events: 28 serious events
Other events: 80 other events
Deaths: 0 deaths
Human Regular U-500 Insulin BID
Serious events: 27 serious events
Other events: 94 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Human Regular U-500 Insulin TID
n=162 participants at risk
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=163 participants at risk
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.9%
3/162 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Atrial fibrillation
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.62%
1/162 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
1.8%
3/163 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Coronary artery disease
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Diastolic dysfunction
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
General disorders
Chest pain
|
1.2%
2/162 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
1.2%
2/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
General disorders
Non-cardiac chest pain
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
General disorders
Oedema peripheral
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
General disorders
Pyrexia
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Cellulitis
|
1.2%
2/162 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Localised infection
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Osteomyelitis
|
0.62%
1/162 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Pharyngotonsillitis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Pneumonia
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
1.8%
3/163 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.9%
3/162 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
3.7%
6/163 • Number of events 6
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer stage i
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.62%
1/162 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Nervous system disorders
Brain injury
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Nervous system disorders
Viith nerve paralysis
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Psychiatric disorders
Post-traumatic stress disorder
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Psychiatric disorders
Suicidal ideation
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
1.2%
2/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
1.2%
2/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.62%
1/162 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Vascular disorders
Aortic stenosis
|
0.62%
1/162 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.00%
0/163
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Vascular disorders
Hypertension
|
0.62%
1/162 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 2
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/162
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
0.61%
1/163 • Number of events 1
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
Other adverse events
| Measure |
Human Regular U-500 Insulin TID
n=162 participants at risk
U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
|
Human Regular U-500 Insulin BID
n=163 participants at risk
U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.7%
6/162 • Number of events 6
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
6.1%
10/163 • Number of events 10
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Nausea
|
2.5%
4/162 • Number of events 4
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
5.5%
9/163 • Number of events 9
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
4/162 • Number of events 4
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
6.7%
11/163 • Number of events 11
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
General disorders
Oedema peripheral
|
3.7%
6/162 • Number of events 6
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
6.1%
10/163 • Number of events 10
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Bronchitis
|
5.6%
9/162 • Number of events 9
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
3.1%
5/163 • Number of events 5
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Nasopharyngitis
|
8.0%
13/162 • Number of events 13
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
10.4%
17/163 • Number of events 17
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.0%
13/162 • Number of events 13
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
5.5%
9/163 • Number of events 9
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.9%
3/162 • Number of events 3
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
6.1%
10/163 • Number of events 10
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Nervous system disorders
Headache
|
8.0%
13/162 • Number of events 13
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
3.7%
6/163 • Number of events 6
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.6%
9/162 • Number of events 9
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
4.3%
7/163 • Number of events 7
The Serious Adverse Events and Other Adverse Events Tables include all randomized participants.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60