Trial Outcomes & Findings for A Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes (NCT NCT00467649)
NCT ID: NCT00467649
Last Updated: 2015-04-14
Results Overview
A severe hypoglycemia is defined as an event during which the patient required the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
112 participants
Primary outcome timeframe
24 Weeks
Results posted on
2015-04-14
Participant Flow
Participant milestones
| Measure |
Group A (Phase 1 SYMLIN)
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group C (Phase 2 SYMLIN)
Patients from Group A, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group D (Phase 2 SYMLIN+RA)
Patients from Group A, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated RA insulin during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Phase 1 (Randomized Population)
STARTED
|
57
|
56
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
Intent to Treat
|
56
|
56
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
COMPLETED
|
48
|
50
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
NOT COMPLETED
|
9
|
6
|
0
|
0
|
0
|
0
|
|
Phase 2 (Intent-to-Treat Population)
STARTED
|
0
|
0
|
17
|
31
|
14
|
36
|
|
Phase 2 (Intent-to-Treat Population)
COMPLETED
|
0
|
0
|
17
|
29
|
14
|
35
|
|
Phase 2 (Intent-to-Treat Population)
NOT COMPLETED
|
0
|
0
|
0
|
2
|
0
|
1
|
Reasons for withdrawal
| Measure |
Group A (Phase 1 SYMLIN)
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group C (Phase 2 SYMLIN)
Patients from Group A, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group D (Phase 2 SYMLIN+RA)
Patients from Group A, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated RA insulin during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Phase 1 (Randomized Population)
Adverse Event
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
Investigator Decision
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
Lost to Follow-up
|
2
|
4
|
0
|
0
|
0
|
0
|
|
Phase 1 (Randomized Population)
Withdrawal of Consent
|
4
|
2
|
0
|
0
|
0
|
0
|
|
Phase 2 (Intent-to-Treat Population)
Lost to Follow-up
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Phase 2 (Intent-to-Treat Population)
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Phase 2 (Intent-to-Treat Population)
Withdrawal of Consent
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Characterize Regimens of Basal Insulin Intensified With Either Symlin® or Rapid Acting Insulin in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
46 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
95 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Age, Continuous
|
55.0 years
STANDARD_DEVIATION 11.35 • n=93 Participants
|
53.6 years
STANDARD_DEVIATION 9.70 • n=4 Participants
|
54.3 years
STANDARD_DEVIATION 10.53 • n=27 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=93 Participants
|
19 Participants
n=4 Participants
|
41 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=93 Participants
|
37 Participants
n=4 Participants
|
71 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=93 Participants
|
56 participants
n=4 Participants
|
112 participants
n=27 Participants
|
|
Fasting Plasma Glucose
|
155.1 mg/dL
STANDARD_DEVIATION 39.60 • n=93 Participants
|
164.3 mg/dL
STANDARD_DEVIATION 49.61 • n=4 Participants
|
159.7 mg/dL
STANDARD_DEVIATION 44.92 • n=27 Participants
|
|
Fasting Serum Lipids
Total Cholesterol
|
167.53 mg/dL
STANDARD_DEVIATION 47.054 • n=93 Participants
|
169.86 mg/dL
STANDARD_DEVIATION 49.121 • n=4 Participants
|
168.70 mg/dL
STANDARD_DEVIATION 47.903 • n=27 Participants
|
|
Fasting Serum Lipids
HDL
|
44.71 mg/dL
STANDARD_DEVIATION 11.893 • n=93 Participants
|
41.77 mg/dL
STANDARD_DEVIATION 9.468 • n=4 Participants
|
43.23 mg/dL
STANDARD_DEVIATION 10.790 • n=27 Participants
|
|
Fasting Serum Lipids
LDL
|
89.15 mg/dL
STANDARD_DEVIATION 38.386 • n=93 Participants
|
90.41 mg/dL
STANDARD_DEVIATION 34.114 • n=4 Participants
|
89.78 mg/dL
STANDARD_DEVIATION 36.133 • n=27 Participants
|
|
Fasting Serum Lipids
Triglycerides
|
174.13 mg/dL
STANDARD_DEVIATION 108.257 • n=93 Participants
|
193.59 mg/dL
STANDARD_DEVIATION 159.508 • n=4 Participants
|
183.95 mg/dL
STANDARD_DEVIATION 136.273 • n=27 Participants
|
|
HbA1c
|
8.19 Percent
STANDARD_DEVIATION 0.840 • n=93 Participants
|
8.25 Percent
STANDARD_DEVIATION 0.816 • n=4 Participants
|
8.22 Percent
STANDARD_DEVIATION 0.825 • n=27 Participants
|
|
Waist Circumference
|
116.31 cm
STANDARD_DEVIATION 15.427 • n=93 Participants
|
117.15 cm
STANDARD_DEVIATION 13.198 • n=4 Participants
|
116.73 cm
STANDARD_DEVIATION 14.297 • n=27 Participants
|
|
Weight
|
107.87 kg
STANDARD_DEVIATION 21.893 • n=93 Participants
|
103.46 kg
STANDARD_DEVIATION 17.908 • n=4 Participants
|
105.67 kg
STANDARD_DEVIATION 20.032 • n=27 Participants
|
PRIMARY outcome
Timeframe: 24 WeeksPopulation: Phase 1 Intent-to-Treat LOCF. LOCF: If a treated patient has missing result value at week 24, then last observed value before week 24 and after baseline is carried forward to impute the week 24 value.
A severe hypoglycemia is defined as an event during which the patient required the assistance of another individual (including aid in ingestion of oral carbohydrate); and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention.
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
The Percentage of Patients Achieving HbA1c <=7% at Week 24 With no Gain in Body Weight From Baseline and no Incidence of Severe Hypoglycemia
|
30.4 Percent
|
10.7 Percent
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 WeeksPopulation: Phase 1 Intent-to-Treat
This is a component of the primary endpoint
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Percentage of Patients Achieving HbA1c <=7% at Week 24
|
44.6 Percent
|
55.4 Percent
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 WeeksPopulation: Phase 1 Intent-to-Treat
This is a component of the primary endpoint
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Percentage of Patients With no Weight Gain at Week 24
|
46.4 Percent
|
14.3 Percent
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 WeeksPopulation: Phase 1 Intent-to-Treat
This is a component of the primary endpoint.
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Percentage of Patients With a Severe Hypoglycemia Adverse Event
|
0.0 Percent
|
0.0 Percent
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: Phase 1 Intent-to-Treat LOCF. LOCF: If a treated patient has missing result value at week 24, then last observed value before week 24 and after baseline is carried forward to impute the week 24 value.
Baseline values are presented in the Baseline Characteristics section
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Change in HbA1c From Baseline at Week 24
|
-1.11 Percent
Standard Error 0.17
|
-1.27 Percent
Standard Error 0.17
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: Phase 1 Intent-to-Treat LOCF. LOCF: If a treated patient has missing result value at week 24, then last observed value before week 24 and after baseline is carried forward to impute the week 24 value.
Baseline values are presented in the Baseline Characteristics section
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Change in Body Weight From Baseline at Week 24
|
0.02 kg
Standard Error 0.68
|
4.65 kg
Standard Error 0.68
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: Phase 1 Intent-to-Treat LOCF. LOCF: If a treated patient has missing result value at week 24, then last observed value before week 24 and after baseline is carried forward to impute the week 24 value.
Baseline values are presented in the Baseline Characteristics section
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=53 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Change in Waist Circumference From Baseline at Week 24
|
-0.63 cm
Standard Error 0.87
|
2.17 cm
Standard Error 0.86
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: Phase 1 Intent-to-Treat
Baseline values are presented in the Baseline Characteristics section
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=45 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=50 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Change in Fasting Plasma Glucose From Baseline at Week 24
|
-29.0 mg/dL
Standard Error 7.32
|
-37.8 mg/dL
Standard Error 7.69
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, week 24Population: Phase 1 Intent-to-Treat
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=47 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=49 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Fasting Serum Lipids Change From Baseline to Week 24
Total Cholesterol
|
-1.81 mg/dL
Standard Error 5.826
|
5.27 mg/dL
Standard Error 4.649
|
—
|
—
|
—
|
—
|
|
Fasting Serum Lipids Change From Baseline to Week 24
HDL
|
1.11 mg/dL
Standard Error 1.190
|
1.65 mg/dL
Standard Error 1.075
|
—
|
—
|
—
|
—
|
|
Fasting Serum Lipids Change From Baseline to Week 24
LDL
|
2.36 mg/dL
Standard Error 4.456
|
9.12 mg/dL
Standard Error 3.865
|
—
|
—
|
—
|
—
|
|
Fasting Serum Lipids Change From Baseline to Week 24
Triglycerides
|
-28.96 mg/dL
Standard Error 12.442
|
-31.98 mg/dL
Standard Error 13.883
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36Population: Phase 2 Intent-to-Treat
Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only).
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=17 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=30 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
n=14 Participants
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=36 Participants
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Phase 2: Change in HbA1c at Week 36
Change From Phase 1 Baseline to Week 36
|
-1.96 Percent
Standard Error 0.238
|
-0.68 Percent
Standard Error 0.174
|
-1.49 Percent
Standard Error 0.189
|
-0.99 Percent
Standard Error 0.157
|
—
|
—
|
|
Phase 2: Change in HbA1c at Week 36
Phase 1 Baseline
|
8.35 Percent
Standard Error 0.214
|
8.03 Percent
Standard Error 0.140
|
7.85 Percent
Standard Error 0.183
|
8.38 Percent
Standard Error 0.145
|
—
|
—
|
|
Phase 2: Change in HbA1c at Week 36
Phase 2 Baseline at Week 24
|
6.26 Percent
Standard Error 0.121
|
7.57 Percent
Standard Error 0.171
|
6.14 Percent
Standard Error 0.107
|
7.32 Percent
Standard Error 0.170
|
—
|
—
|
|
Phase 2: Change in HbA1c at Week 36
Change From Phase 2 Baseline to Week 36
|
0.14 Percent
Standard Error 0.062
|
-0.23 Percent
Standard Error 0.123
|
0.22 Percent
Standard Error 0.097
|
0.07 Percent
Standard Error 0.113
|
—
|
—
|
SECONDARY outcome
Timeframe: Phase 1 Baseline, Phase 2 Baseline at Week 24, Week 36Population: Phase 2 Intent-to-Treat
Two changes are calculated, the first by subtracting Week 36 value from the Phase 1 Baseline value (total change over 36 weeks), the second by subtracting the Week 36 value from the Phase 2 Baseline value (change from week 24 to week 36 only).
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=17 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=30 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
n=14 Participants
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=36 Participants
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Phase 2: Change in Body Weight at Week 36
Phase 1 Baseline
|
109.98 kg
Standard Error 4.916
|
104.83 kg
Standard Error 3.959
|
104.42 kg
Standard Error 7.341
|
105.30 kg
Standard Error 2.210
|
—
|
—
|
|
Phase 2: Change in Body Weight at Week 36
Change From Phase 1 Baseline to Week 36
|
-0.80 kg
Standard Error 2.096
|
1.34 kg
Standard Error 0.933
|
3.90 kg
Standard Error 1.488
|
4.51 kg
Standard Error 0.761
|
—
|
—
|
|
Phase 2: Change in Body Weight at Week 36
Phase 2 Baseline at Week 24
|
108.50 kg
Standard Error 5.656
|
105.67 kg
Standard Error 4.045
|
107.87 kg
Standard Error 7.801
|
110.68 kg
Standard Error 2.507
|
—
|
—
|
|
Phase 2: Change in Body Weight at Week 36
Change From Phase 2 Baseline to Week 36
|
0.69 kg
Standard Error 0.654
|
0.50 kg
Standard Error 0.303
|
0.44 kg
Standard Error 0.518
|
-0.86 kg
Standard Error 0.353
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 36 weeksMILD: patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms did not greatly interrupt or interfere with the patients daily activities. Symptoms dissipated spontaneously or upon eating. MODERATE: Patient reported symptoms consistent with hypoglycemia that may or may not have been documented by glucose monitoring at the time of symptoms. Symptoms interrupted or interfered with the patients daily activities and required immediate self treatment (e.g. carbohydrate ingestion). SEVERE: Patient required the assistance of another individual (including aid in ingestion of oral carbohydrate): and/or required the administration of glucagon injection, intravenous glucose, or other medical intervention.
Outcome measures
| Measure |
Group A (Phase 1 SYMLIN)
n=56 Participants
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 Participants
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group E (Phase 2 RA Insulin)
n=17 Participants
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=31 Participants
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
Group E (Phase 2 RA Insulin)
n=14 Participants
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=36 Participants
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Hypoglycemia Adverse Events
Mild
|
31 participants
|
46 participants
|
7 participants
|
18 participants
|
9 participants
|
19 participants
|
|
Hypoglycemia Adverse Events
Moderate
|
12 participants
|
13 participants
|
0 participants
|
1 participants
|
2 participants
|
3 participants
|
|
Hypoglycemia Adverse Events
Severe
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Group A (Phase 1 SYMLIN)
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Group B (Phase 1 RA Insulin)
Serious events: 5 serious events
Other events: 28 other events
Deaths: 0 deaths
Group C (Phase 2 SYMLIN)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Group D (Phase 2 SYMLIN+RA)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Group E (Phase 2 RA Insulin)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group F (Phase 2 RA Insulin + SYMLIN)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group A (Phase 1 SYMLIN)
n=56 participants at risk
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 participants at risk
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group C (Phase 2 SYMLIN)
n=17 participants at risk
Patients from Group A, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group D (Phase 2 SYMLIN+RA)
n=31 participants at risk
Patients from Group A, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated RA insulin during Phase 2
|
Group E (Phase 2 RA Insulin)
n=14 participants at risk
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=36 participants at risk
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
1.8%
1/56 • Number of events 1
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Hepatobiliary disorders
Biliary dyskinesia
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Nervous system disorders
Syncope
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Cellulitis
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Nervous system disorders
Ischaemic cerebral infarction
|
0.00%
0/56
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
Other adverse events
| Measure |
Group A (Phase 1 SYMLIN)
n=56 participants at risk
SYMLIN treatment (120 mcg prior to major meals) was initiated on Day 1. Basal insulin was titrated throughout the study
|
Group B (Phase 1 RA Insulin)
n=56 participants at risk
Rapid acting insulin (RA Insulin: variable dosing, titrated to optimize postprandial glucose control) was initiated at Week 4. Basal insulin was titrated throughout the study
|
Group C (Phase 2 SYMLIN)
n=17 participants at risk
Patients from Group A, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group D (Phase 2 SYMLIN+RA)
n=31 participants at risk
Patients from Group A, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated RA insulin during Phase 2
|
Group E (Phase 2 RA Insulin)
n=14 participants at risk
Patients from Group B, who achieved HbA1c goal at Week 24, continued Phase 1 treatment during Phase 2
|
Group F (Phase 2 RA Insulin + SYMLIN)
n=36 participants at risk
Patients from Group B, who did not achieve HbA1c goal at Week 24, continued Phase 1 treatment and initiated SYMLIN during Phase 2
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
21.4%
12/56 • Number of events 16
|
0.00%
0/56
|
0.00%
0/17
|
6.5%
2/31 • Number of events 2
|
0.00%
0/14
|
11.1%
4/36 • Number of events 4
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
5/56 • Number of events 7
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
5.6%
2/36 • Number of events 2
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Gastrointestinal disorders
Peptic ulcer
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
General disorders
Chest pain
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 2
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
General disorders
Oedema peripheral
|
0.00%
0/56
|
7.1%
4/56 • Number of events 5
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
3/56 • Number of events 3
|
8.9%
5/56 • Number of events 5
|
5.9%
1/17 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
0.00%
0/36
|
|
Infections and infestations
Bronchitis
|
0.00%
0/56
|
0.00%
0/56
|
0.00%
0/17
|
9.7%
3/31 • Number of events 3
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Influenza
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
6.5%
2/31 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
0.00%
0/36
|
|
Infections and infestations
Otitis externa
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Sinusitis
|
3.6%
2/56 • Number of events 2
|
8.9%
5/56 • Number of events 5
|
5.9%
1/17 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
0.00%
0/14
|
2.8%
1/36 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
7/56 • Number of events 8
|
8.9%
5/56 • Number of events 5
|
5.9%
1/17 • Number of events 1
|
6.5%
2/31 • Number of events 2
|
7.1%
1/14 • Number of events 2
|
2.8%
1/36 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
5.4%
3/56 • Number of events 3
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/56
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
5.6%
2/36 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
5.4%
3/56 • Number of events 3
|
3.6%
2/56 • Number of events 2
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/56
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
7.1%
1/14 • Number of events 1
|
0.00%
0/36
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/56
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
7.1%
1/14 • Number of events 1
|
0.00%
0/36
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/56
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
5.6%
2/36 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
2.8%
1/36 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
3/56 • Number of events 4
|
8.9%
5/56 • Number of events 7
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.9%
5/56 • Number of events 5
|
0.00%
0/56
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/56
|
5.4%
3/56 • Number of events 3
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/56
|
5.4%
3/56 • Number of events 3
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Nervous system disorders
Headache
|
8.9%
5/56 • Number of events 11
|
1.8%
1/56 • Number of events 1
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.6%
2/56 • Number of events 2
|
8.9%
5/56 • Number of events 5
|
0.00%
0/17
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/56
|
0.00%
0/56
|
5.9%
1/17 • Number of events 1
|
0.00%
0/31
|
0.00%
0/14
|
0.00%
0/36
|
|
Vascular disorders
Hypertension
|
0.00%
0/56
|
8.9%
5/56 • Number of events 5
|
0.00%
0/17
|
6.5%
2/31 • Number of events 3
|
7.1%
1/14 • Number of events 1
|
5.6%
2/36 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60