Trial Outcomes & Findings for A Study of Dose Titration of LY2189265 in Overweight Participants With Type 2 Diabetes Mellitus (NCT NCT00630825)
NCT ID: NCT00630825
Last Updated: 2014-12-10
Results Overview
Once weekly injections of LY2189265 (titrated and non-titrated doses) compared to placebo on blood glucose were evaluated. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline glycosylated hemoglobin (HbA1c).
COMPLETED
PHASE2
262 participants
Baseline, 16 weeks
2014-12-10
Participant Flow
Participant milestones
| Measure |
1.0/2.0 Milligram (mg) LY2189265
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
65
|
65
|
66
|
66
|
|
Overall Study
Received at Least One Dose of Study Drug
|
65
|
65
|
66
|
66
|
|
Overall Study
COMPLETED
|
56
|
58
|
58
|
60
|
|
Overall Study
NOT COMPLETED
|
9
|
7
|
8
|
6
|
Reasons for withdrawal
| Measure |
1.0/2.0 Milligram (mg) LY2189265
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
4
|
3
|
1
|
|
Overall Study
Entry Criteria Not Met
|
1
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
2
|
3
|
Baseline Characteristics
A Study of Dose Titration of LY2189265 in Overweight Participants With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
Total
n=262 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.49 years
STANDARD_DEVIATION 11.28 • n=5 Participants
|
57.46 years
STANDARD_DEVIATION 11.72 • n=7 Participants
|
58.65 years
STANDARD_DEVIATION 11.69 • n=5 Participants
|
55.96 years
STANDARD_DEVIATION 12.49 • n=4 Participants
|
56.65 years
STANDARD_DEVIATION 11.84 • n=21 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
129 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
133 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
African
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
4 participants
n=4 Participants
|
19 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
36 participants
n=5 Participants
|
39 participants
n=7 Participants
|
40 participants
n=5 Participants
|
36 participants
n=4 Participants
|
151 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
23 participants
n=5 Participants
|
20 participants
n=7 Participants
|
19 participants
n=5 Participants
|
26 participants
n=4 Participants
|
88 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=5 Participants
|
56 participants
n=7 Participants
|
57 participants
n=5 Participants
|
58 participants
n=4 Participants
|
227 participants
n=21 Participants
|
|
Region of Enrollment
Puerto Rico
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
9 participants
n=5 Participants
|
8 participants
n=4 Participants
|
35 participants
n=21 Participants
|
|
Glycosylated Hemoglobin (HbA1c)
|
8.43 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.99 • n=5 Participants
|
8.25 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.99 • n=7 Participants
|
8.25 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.89 • n=5 Participants
|
8.05 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.82 • n=4 Participants
|
8.24 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.93 • n=21 Participants
|
|
Body Mass Index (BMI)
|
34.24 kilograms per square meters (kg/m^2)
STANDARD_DEVIATION 4.11 • n=5 Participants
|
33.85 kilograms per square meters (kg/m^2)
STANDARD_DEVIATION 3.95 • n=7 Participants
|
33.70 kilograms per square meters (kg/m^2)
STANDARD_DEVIATION 4.11 • n=5 Participants
|
33.89 kilograms per square meters (kg/m^2)
STANDARD_DEVIATION 4.31 • n=4 Participants
|
33.92 kilograms per square meters (kg/m^2)
STANDARD_DEVIATION 4.10 • n=21 Participants
|
|
Body Weight
|
98.60 kilograms (kg)
STANDARD_DEVIATION 18.41 • n=5 Participants
|
96.68 kilograms (kg)
STANDARD_DEVIATION 16.51 • n=7 Participants
|
94.76 kilograms (kg)
STANDARD_DEVIATION 16.53 • n=5 Participants
|
94.74 kilograms (kg)
STANDARD_DEVIATION 15.21 • n=4 Participants
|
96.18 kilograms (kg)
STANDARD_DEVIATION 16.68 • n=21 Participants
|
|
Duration of Diabetes
|
8.63 years
STANDARD_DEVIATION 6.92 • n=5 Participants
|
8.13 years
STANDARD_DEVIATION 5.43 • n=7 Participants
|
8.97 years
STANDARD_DEVIATION 7.62 • n=5 Participants
|
7.48 years
STANDARD_DEVIATION 5.41 • n=4 Participants
|
8.30 years
STANDARD_DEVIATION 6.41 • n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Once weekly injections of LY2189265 (titrated and non-titrated doses) compared to placebo on blood glucose were evaluated. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline glycosylated hemoglobin (HbA1c).
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=62 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=63 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=65 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) in Overweight and Obese Participants With Type 2 Diabetes Mellitus
|
-1.52 percentage of glycosylated hemoglobin
Standard Error 0.12
|
-1.29 percentage of glycosylated hemoglobin
Standard Error 0.12
|
-1.28 percentage of glycosylated hemoglobin
Standard Error 0.12
|
-0.27 percentage of glycosylated hemoglobin
Standard Error 0.12
|
SECONDARY outcome
Timeframe: Baseline, 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable fasting blood glucose data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means of change were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=51 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=52 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=48 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=53 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Fasting Blood Glucose
|
-2.64 millimoles per liter (mmol/L)
Standard Error 0.33
|
-2.04 millimoles per liter (mmol/L)
Standard Error 0.34
|
-2.09 millimoles per liter (mmol/L)
Standard Error 0.34
|
-0.49 millimoles per liter (mmol/L)
Standard Error 0.32
|
SECONDARY outcome
Timeframe: Baseline and 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable glucose excursion data.
Glucose excursion in response to a standardized solid mixed meal test was evaluated at baseline (randomization) and at Week 16, or at early termination. Each of the 2 standardized meal tests required participants to fast starting at 2200 hours the night prior to the test. A standardized breakfast meal was provided to the participant (approximately 550 kilocalorie \[Kcal\], 103 grams \[g\] carbohydrates, 22 g protein, and 8.5 g fat) and was to be consumed within 15 minutes. Serial venous blood samples were taken at the start of the meal (fasting \[0\]) and 30, 60, 90, 120, and 180 minutes after the start of the meal. Least Squares (LS) means of change in mean glucose area under the curve excursion following a test meal were calculated adjusting for treatment, combination of oral medications, and baseline.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=52 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=56 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=54 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=59 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal)
Baseline (n=63, n=62, n=66, n=63)
|
11.03 millimoles per liter (mmol/L)*minute
Standard Deviation 5.02
|
11.12 millimoles per liter (mmol/L)*minute
Standard Deviation 4.77
|
10.32 millimoles per liter (mmol/L)*minute
Standard Deviation 4.93
|
10.76 millimoles per liter (mmol/L)*minute
Standard Deviation 4.37
|
|
Meal Test Glucose Excursion (Change in Blood Glucose to Test Meal)
Week 16 (n=52, n=56, n=54, n=59)
|
8.16 millimoles per liter (mmol/L)*minute
Standard Deviation 4.58
|
9.92 millimoles per liter (mmol/L)*minute
Standard Deviation 5.32
|
8.85 millimoles per liter (mmol/L)*minute
Standard Deviation 4.94
|
10.94 millimoles per liter (mmol/L)*minute
Standard Deviation 4.79
|
SECONDARY outcome
Timeframe: 2 separate days in the week preceding the Baseline, Week 4, Week 8, and Week 16 visits.Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable blood glucose (SMBG) data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Change from baseline in mean daily blood glucose values were measured using self-monitored blood glucose (SMBG) data collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 2:00 am. The daily mean was calculated as the average of the 8 blood glucose values collected on a particular day. Least Squares (LS) means of change from baseline of the mean of the 8 time points (Daily Mean) were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=41 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=50 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=46 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=49 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles
Week 4 (n=34, n=38, n=35, n=41)
|
-31.19 milligrams per deciliter (mg/dL)
Standard Error 5.85
|
-35.94 milligrams per deciliter (mg/dL)
Standard Error 5.30
|
-31.66 milligrams per deciliter (mg/dL)
Standard Error 5.36
|
-8.10 milligrams per deciliter (mg/dL)
Standard Error 5.06
|
|
Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles
Week 8 (n=34, n=41, n=38, n=41)
|
-43.00 milligrams per deciliter (mg/dL)
Standard Error 5.88
|
-40.68 milligrams per deciliter (mg/dL)
Standard Error 5.43
|
-36.02 milligrams per deciliter (mg/dL)
Standard Error 5.35
|
-14.58 milligrams per deciliter (mg/dL)
Standard Error 5.38
|
|
Change From Baseline in Daily Mean Blood Glucose Values From the 8-point Self Monitored Blood Glucose (SMBG) Profiles
Week 16 (n=41, n=50, n=46, n=49)
|
-37.49 milligrams per deciliter (mg/dL)
Standard Error 5.89
|
-41.79 milligrams per deciliter (mg/dL)
Standard Error 5.25
|
-32.52 milligrams per deciliter (mg/dL)
Standard Error 5.40
|
-8.67 milligrams per deciliter (mg/dL)
Standard Error 5.30
|
SECONDARY outcome
Timeframe: Baseline, 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable HOMA2-%B or HOMA2-%S data.
Homeostasis Model Assessment tool (HOMA2) of β-cell function is a technique for estimating beta-cell function (HOMA2-%B) and insulin sensitivity (HOMA2-%S) using basal serum glucose, and c-peptide concentrations. A fasting blood glucose, c-peptide, and serum insulin level were drawn for purposes of this determination just prior to the mixed meal test.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=48 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=48 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=48 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=47 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2)
HOMA2-%B
|
45.61 percentage of HOMA2
Standard Deviation 55.20
|
44.26 percentage of HOMA2
Standard Deviation 93.89
|
39.20 percentage of HOMA2
Standard Deviation 45.56
|
1.04 percentage of HOMA2
Standard Deviation 41.12
|
|
Change From Baseline in Beta (β)-Cell Function and Insulin Sensitivity as Estimated by the Updated Homeostasis Model Assessment Method (HOMA2)
HOMA2-%S
|
3.58 percentage of HOMA2
Standard Deviation 18.51
|
-1.65 percentage of HOMA2
Standard Deviation 17.19
|
0.46 percentage of HOMA2
Standard Deviation 13.78
|
2.46 percentage of HOMA2
Standard Deviation 12.23
|
SECONDARY outcome
Timeframe: Baseline and 4 and 8 and 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of \<7% or ≤6.5% were analyzed with a logistic regression model with baseline, combination of oral medications, and treatment as factors included in the model.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels <7.0%, Baseline
|
3.1 percentage of participants
|
4.6 percentage of participants
|
1.5 percentage of participants
|
4.5 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels ≤6.5%, Baseline
|
0.0 percentage of participants
|
1.5 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels <7.0%, Week 4
|
15.4 percentage of participants
|
30.8 percentage of participants
|
22.7 percentage of participants
|
7.6 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels ≤6.5%, Week 4
|
4.6 percentage of participants
|
7.7 percentage of participants
|
3.0 percentage of participants
|
1.5 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels <7%, Week 8
|
41.5 percentage of participants
|
47.7 percentage of participants
|
47.0 percentage of participants
|
15.2 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels ≤6.5%, Week 8
|
20.0 percentage of participants
|
26.2 percentage of participants
|
18.2 percentage of participants
|
1.5 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels <7%, Week 16
|
53.8 percentage of participants
|
50.8 percentage of participants
|
56.1 percentage of participants
|
15.2 percentage of participants
|
|
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
HbA1c levels ≤6.5%, Week 16
|
32.3 percentage of participants
|
32.3 percentage of participants
|
33.3 percentage of participants
|
4.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 4, 8, and 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable body weight data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
LS means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusting for treatment, combination of oral medications, and baseline.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=63 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=63 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=65 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Body Weight
4 weeks (n=63, n=63, n=65, n=65)
|
-1.28 kilograms (kg)
Standard Error 0.23
|
-1.08 kilograms (kg)
Standard Error 0.23
|
-0.50 kilograms (kg)
Standard Error 0.22
|
-0.06 kilograms (kg)
Standard Error 0.22
|
|
Change From Baseline in Body Weight
8 weeks (n=61, n=60, n=63, n=64)
|
-2.12 kilograms (kg)
Standard Error 0.31
|
-1.67 kilograms (kg)
Standard Error 0.32
|
-1.39 kilograms (kg)
Standard Error 0.31
|
-0.12 kilograms (kg)
Standard Error 0.31
|
|
Change From Baseline in Body Weight
16 weeks (n=63, n=63, n=65, n=65)
|
-2.51 kilograms (kg)
Standard Error 0.38
|
-1.40 kilograms (kg)
Standard Error 0.38
|
-1.58 kilograms (kg)
Standard Error 0.37
|
-0.07 kilograms (kg)
Standard Error 0.38
|
SECONDARY outcome
Timeframe: Baseline, 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable waist circumference data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Mean change from baseline in waist circumference (a measure of central obesity).
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=59 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=60 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=63 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=60 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Waist Circumference
|
-1.92 centimeters (cm)
Standard Deviation 4.24
|
-1.51 centimeters (cm)
Standard Deviation 4.56
|
-1.33 centimeters (cm)
Standard Deviation 4.21
|
0.20 centimeters (cm)
Standard Deviation 3.40
|
SECONDARY outcome
Timeframe: One week before and one week after each of the Baseline and Week 4 and Week 8 and Week 16 visitsPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable nausea or dyspepsia (abdominal pain and bloating) data.
Participants were asked to score nausea and dyspepsia (abdominal pain and bloating) on a scale of 0 (none) to 100 after the largest meal of the day.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week before Baseline (n=52, 57, 61, 57)
|
4.81 units on a scale
Standard Deviation 10.50
|
3.56 units on a scale
Standard Deviation 6.46
|
3.70 units on a scale
Standard Deviation 5.76
|
3.35 units on a scale
Standard Deviation 5.83
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week after Baseline (n=42, 46, 50, 50)
|
5.07 units on a scale
Standard Deviation 8.58
|
3.85 units on a scale
Standard Deviation 6.46
|
3.86 units on a scale
Standard Deviation 5.96
|
2.25 units on a scale
Standard Deviation 4.82
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week before Baseline (n=52, 57, 61, 57)
|
5.66 units on a scale
Standard Deviation 11.37
|
3.55 units on a scale
Standard Deviation 9.14
|
4.04 units on a scale
Standard Deviation 7.15
|
3.63 units on a scale
Standard Deviation 6.58
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week after Baseline (n=42, 46, 50, 50)
|
5.82 units on a scale
Standard Deviation 9.41
|
4.89 units on a scale
Standard Deviation 13.35
|
4.51 units on a scale
Standard Deviation 8.60
|
2.86 units on a scale
Standard Deviation 7.27
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week before Baseline (n=52, 57, 61, 57)
|
11.49 units on a scale
Standard Deviation 16.80
|
8.11 units on a scale
Standard Deviation 18.04
|
10.21 units on a scale
Standard Deviation 15.32
|
9.30 units on a scale
Standard Deviation 18.65
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week after Baseline (n=42, 46, 50, 50)
|
8.95 units on a scale
Standard Deviation 12.90
|
10.10 units on a scale
Standard Deviation 16.64
|
9.17 units on a scale
Standard Deviation 15.61
|
8.42 units on a scale
Standard Deviation 20.05
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week before Week 4 (n=42, 55, 52, 59)
|
6.74 units on a scale
Standard Deviation 10.89
|
6.88 units on a scale
Standard Deviation 11.47
|
7.97 units on a scale
Standard Deviation 15.33
|
4.10 units on a scale
Standard Deviation 7.32
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week after Week 4 (n=49, 58, 59, 54)
|
18.13 units on a scale
Standard Deviation 24.52
|
12.28 units on a scale
Standard Deviation 19.46
|
7.91 units on a scale
Standard Deviation 12.39
|
4.10 units on a scale
Standard Deviation 7.57
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week before Week 4 (n=42, 55, 52, 59)
|
6.28 units on a scale
Standard Deviation 9.53
|
7.74 units on a scale
Standard Deviation 13.89
|
6.38 units on a scale
Standard Deviation 11.13
|
4.45 units on a scale
Standard Deviation 9.19
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week after Week 4 (n=49, 58, 59, 54)
|
12.47 units on a scale
Standard Deviation 20.44
|
9.31 units on a scale
Standard Deviation 15.77
|
4.94 units on a scale
Standard Deviation 8.89
|
4.59 units on a scale
Standard Deviation 7.88
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week before Week 4 (n=42, 55, 52, 59)
|
13.56 units on a scale
Standard Deviation 19.51
|
12.00 units on a scale
Standard Deviation 19.17
|
9.95 units on a scale
Standard Deviation 13.27
|
7.96 units on a scale
Standard Deviation 15.77
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week after Week 4 (n=49, 58, 59, 54)
|
19.90 units on a scale
Standard Deviation 25.61
|
13.40 units on a scale
Standard Deviation 21.15
|
10.23 units on a scale
Standard Deviation 13.88
|
8.40 units on a scale
Standard Deviation 14.96
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week before Week 8 (n=50, 51, 55, 58)
|
10.90 units on a scale
Standard Deviation 20.26
|
5.45 units on a scale
Standard Deviation 10.63
|
7.39 units on a scale
Standard Deviation 13.53
|
6.11 units on a scale
Standard Deviation 12.59
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week after Week 8 (n=50, 54, 54, 55)
|
8.58 units on a scale
Standard Deviation 12.88
|
5.57 units on a scale
Standard Deviation 11.50
|
8.69 units on a scale
Standard Deviation 13.41
|
5.30 units on a scale
Standard Deviation 11.52
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week before Week 8 (n=50, 51, 55, 58)
|
10.76 units on a scale
Standard Deviation 19.06
|
5.76 units on a scale
Standard Deviation 12.47
|
5.12 units on a scale
Standard Deviation 9.01
|
6.65 units on a scale
Standard Deviation 13.15
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week after Week 8 (n=50, 54, 54, 55)
|
7.97 units on a scale
Standard Deviation 14.72
|
6.87 units on a scale
Standard Deviation 14.56
|
6.26 units on a scale
Standard Deviation 11.93
|
6.38 units on a scale
Standard Deviation 12.74
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week before Week 8 (n=50, 51, 55, 58)
|
17.65 units on a scale
Standard Deviation 26.41
|
10.93 units on a scale
Standard Deviation 17.92
|
11.58 units on a scale
Standard Deviation 20.13
|
10.12 units on a scale
Standard Deviation 19.20
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week after Week 8 (n=50, 54, 54, 55)
|
13.30 units on a scale
Standard Deviation 18.66
|
11.18 units on a scale
Standard Deviation 19.56
|
14.50 units on a scale
Standard Deviation 20.95
|
10.34 units on a scale
Standard Deviation 17.17
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week before Week 16 (n=45, 49, 52, 54)
|
9.68 units on a scale
Standard Deviation 17.79
|
3.31 units on a scale
Standard Deviation 5.53
|
6.36 units on a scale
Standard Deviation 10.82
|
5.88 units on a scale
Standard Deviation 14.41
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Nausea, Week after Week 16 (n=45, 48, 49, 53)
|
11.09 units on a scale
Standard Deviation 17.62
|
5.73 units on a scale
Standard Deviation 10.80
|
7.77 units on a scale
Standard Deviation 12.25
|
3.40 units on a scale
Standard Deviation 6.40
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week before Week 16 (n=45, 49, 52, 54)
|
6.46 units on a scale
Standard Deviation 9.48
|
5.68 units on a scale
Standard Deviation 11.09
|
6.26 units on a scale
Standard Deviation 12.89
|
6.17 units on a scale
Standard Deviation 14.24
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Ab pain, Week after Week 16 (n=45, 48, 49, 53)
|
7.56 units on a scale
Standard Deviation 14.28
|
5.99 units on a scale
Standard Deviation 11.53
|
6.44 units on a scale
Standard Deviation 12.58
|
5.19 units on a scale
Standard Deviation 11.72
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week before Week 16 (n=45, 49, 52, 54)
|
12.57 units on a scale
Standard Deviation 18.93
|
9.06 units on a scale
Standard Deviation 16.78
|
12.26 units on a scale
Standard Deviation 20.06
|
9.30 units on a scale
Standard Deviation 18.60
|
|
Nausea and Dyspepsia Measured by Visual Analog Scale
Bloating, Week after Week 16 (n=45, 48, 49, 53)
|
14.06 units on a scale
Standard Deviation 20.46
|
11.11 units on a scale
Standard Deviation 19.62
|
14.04 units on a scale
Standard Deviation 22.26
|
8.84 units on a scale
Standard Deviation 17.44
|
SECONDARY outcome
Timeframe: Baseline and 4 and 8 and 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable Gastroparesis Cardinal Symptom Index (GCSI) questionnaire data. For Week 16 data, last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Gastroparesis Cardinal Symptom Index (GCSI) is a participant-completed questionnaire designed to assess the severity of symptoms consistent with delayed gastric emptying (nausea/vomiting, abdominal bloating, and stomach fullness) at each study visit. GCSI scores ranged from 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, to 5=very severe.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Stomach fullness, Week 4 (n=62, n=60, n=65, n=65)
|
0.55 units on a scale
Standard Deviation 1.51
|
0.57 units on a scale
Standard Deviation 1.35
|
0.62 units on a scale
Standard Deviation 1.26
|
0.35 units on a scale
Standard Deviation 1.39
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Stomach fullness, Week 8 (n=59, n=60, n=59, n=63)
|
0.46 units on a scale
Standard Deviation 1.65
|
0.30 units on a scale
Standard Deviation 1.33
|
0.71 units on a scale
Standard Deviation 1.54
|
0.25 units on a scale
Standard Deviation 1.39
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Stomach fullness, Week 16 (n=63, n=62, n=65, n=65)
|
0.21 units on a scale
Standard Deviation 1.58
|
0.27 units on a scale
Standard Deviation 1.28
|
0.51 units on a scale
Standard Deviation 1.34
|
0.15 units on a scale
Standard Deviation 1.34
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Bloating, Week 4 (n=62, n=60, n=65, n=65)
|
0.35 units on a scale
Standard Deviation 0.10
|
0.28 units on a scale
Standard Deviation 0.93
|
0.19 units on a scale
Standard Deviation 0.91
|
0.28 units on a scale
Standard Deviation 0.84
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Bloating, Week 8 (n=59, n=60, n=60, n=63)
|
0.41 units on a scale
Standard Deviation 1.34
|
0.13 units on a scale
Standard Deviation 1.02
|
0.14 units on a scale
Standard Deviation 1.32
|
0.18 units on a scale
Standard Deviation 0.92
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Bloating, Week 16 (n=63, n=62, n=65, n=65)
|
0.02 units on a scale
Standard Deviation 1.04
|
0.11 units on a scale
Standard Deviation 0.94
|
0.32 units on a scale
Standard Deviation 1.32
|
0.28 units on a scale
Standard Deviation 0.86
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Nausea/Vomiting, Week 4 (n=62, n=60, n=64, n=65)
|
0.25 units on a scale
Standard Deviation 0.71
|
0.19 units on a scale
Standard Deviation 0.71
|
0.22 units on a scale
Standard Deviation 0.52
|
0.03 units on a scale
Standard Deviation 0.40
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Nausea/Vomiting, Week 8 (n=59, n=60, n=60, n=63)
|
0.46 units on a scale
Standard Deviation 0.97
|
0.04 units on a scale
Standard Deviation 0.64
|
0.28 units on a scale
Standard Deviation 0.62
|
0.02 units on a scale
Standard Deviation 0.39
|
|
Change From Baseline in Gastroparesis Cardinal Symptom Index (GCSI) Scores
Nausea/Vomiting, Week 16 (n=63, n=62, n=65, n=65)
|
0.20 units on a scale
Standard Deviation 0.64
|
-0.01 units on a scale
Standard Deviation 0.59
|
0.27 units on a scale
Standard Deviation 0.48
|
-0.01 units on a scale
Standard Deviation 0.36
|
SECONDARY outcome
Timeframe: Baseline through 4, 8, and 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo.
A documented hypoglycemic episode is defined as an event which is associated with a measured blood glucose of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. A severe hypoglycemic episode is defined as an event with a measured blood glucose of \<50mg/dL. Participant reports of hypoglycemic events were collected at the beginning of each visit starting at Baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Number of Participants With a Hypoglycemic Event
Documented Hypoglycemic Event, Week 4
|
17 participants
|
17 participants
|
17 participants
|
9 participants
|
|
Number of Participants With a Hypoglycemic Event
Documented Hypoglycemic Event, Week 8
|
11 participants
|
13 participants
|
15 participants
|
10 participants
|
|
Number of Participants With a Hypoglycemic Event
Documented Hypoglycemic Event, Week 16
|
6 participants
|
10 participants
|
7 participants
|
8 participants
|
|
Number of Participants With a Hypoglycemic Event
Severe Hypoglycemic Event, Week 4
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Hypoglycemic Event
Severe Hypoglycemic Event, Week 8
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Hypoglycemic Event
Severe Hypoglycemic Event, Week 16
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline through 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo.
Hypoglycemic episodes are defined as an event which is associated with reported signs and/or symptoms of hypoglycemia (for example, sweating, shakiness, tachycardia, etc.) or a documented blood glucose (BG) concentration of ≤70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]), even if it was not associated with symptoms, signs, or treatment. The rate is the average number of days out of 30 that a participant reported hypoglycemia. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Rate of Hypoglycemia Per 30 Days
|
0.69 events per participant per 30 days
Standard Deviation 1.29
|
0.80 events per participant per 30 days
Standard Deviation 1.60
|
0.70 events per participant per 30 days
Standard Deviation 1.18
|
0.24 events per participant per 30 days
Standard Deviation 0.54
|
SECONDARY outcome
Timeframe: Baseline, 16 weeksPopulation: Participants who received at least one dose of LY2189265 or Placebo with evaluable lipid data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Lipids include total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Lipids
Cholesterol (n=61, n=60, n=60, n=62)
|
-0.34 millimoles per liter (mmol/L)
Interval -3.44 to 2.28
|
-0.05 millimoles per liter (mmol/L)
Interval -1.37 to 2.69
|
-0.09 millimoles per liter (mmol/L)
Interval -2.18 to 4.77
|
0.18 millimoles per liter (mmol/L)
Interval -1.91 to 2.56
|
|
Change From Baseline in Lipids
LDL-Cholesterol (n=61, n=60, n=60, n=61)
|
-0.26 millimoles per liter (mmol/L)
Interval -2.8 to 2.23
|
-0.09 millimoles per liter (mmol/L)
Interval -1.22 to 1.58
|
-0.07 millimoles per liter (mmol/L)
Interval -1.39 to 4.27
|
0.10 millimoles per liter (mmol/L)
Interval -0.83 to 2.12
|
|
Change From Baseline in Lipids
HDL-Cholesterol (n=61, n=60, n=60, n=61)
|
-0.02 millimoles per liter (mmol/L)
Interval -0.33 to 0.41
|
-0.02 millimoles per liter (mmol/L)
Interval -0.37 to 0.54
|
0.00 millimoles per liter (mmol/L)
Interval -0.26 to 0.23
|
0.00 millimoles per liter (mmol/L)
Interval -0.24 to 0.26
|
|
Change From Baseline in Lipids
Triglycerides (n=61, n=60, n=60, n=61)
|
-0.16 millimoles per liter (mmol/L)
Interval -7.63 to 2.22
|
-0.02 millimoles per liter (mmol/L)
Interval -4.84 to 2.96
|
-0.16 millimoles per liter (mmol/L)
Interval -4.25 to 2.96
|
0.00 millimoles per liter (mmol/L)
Interval -7.39 to 5.69
|
SECONDARY outcome
Timeframe: Baseline and 4 and 8 and 16 weeksPopulation: Participants in the per-protocol population with evaluable PAM-D-S questionnaire data. The per-protocol population consisted of participants who received at least one dose of study medication, had no significant protocol violations, completed the double-blind treatment phase, and were compliant with the study drug.
The Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire consisted of: 2 items in which respondents were asked about their satisfaction with their diabetes medication over the past week using a 6-point scale ranging from 1 "completely dissatisfied" to 6 "completely satisfied"; 10 items in which respondents were asked about the effectiveness of their diabetes medications in the past week using a 4-point scale ranging from 1 "all of the time" to 4 "none of the time"; and 15 items asking respondents to indicate the frequency of physical side effects in the past week using a 4-point scale ranging from 1 "all of the time" to 4 "none of the time." These items were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. The percentage of participants that rated their general health as good or better are summarized.
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=55 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=58 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=59 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=58 Participants
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
Baseline
|
72.7 percentage of participants
|
87.0 percentage of participants
|
87.5 percentage of participants
|
89.1 percentage of participants
|
|
Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
Week 4
|
83.3 percentage of participants
|
90.2 percentage of participants
|
87.5 percentage of participants
|
87.0 percentage of participants
|
|
Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
Week 8
|
82.9 percentage of participants
|
90.5 percentage of participants
|
90.9 percentage of participants
|
88.6 percentage of participants
|
|
Participants Perception of Medication Effectiveness Using the Perceptions About Medications - Diabetes, Short Version (PAM-D-S) Questionnaire
Week 16
|
92.1 percentage of participants
|
90.2 percentage of participants
|
86.0 percentage of participants
|
93.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and 4 and 8 and 16 weeksPopulation: The items in the Perceptions about Medications - Diabetes, Short Version (PAM-D-S) questionnaire were exploratory items taken from a Diabetes Medicines Survey and had not been validated as a scale. Therefore, no participants were analyzed for validation purposes.
This purpose of this outcome measure was to validate the PAM-D-S questionnaire for future use. Please refer to Outcome Measure #14 for a description of the PAM-D-S questionnaire and results collected. A preliminary analysis indicated modifications to the questionnaire were required and further study is necessary to complete the validation. Therefore, the PAM-D-S questionnaire was not validated as a part of Study H9X-MC-GBCJ.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time zero to 168 hours after study drug administration at 4, 8, and 16 weeksPopulation: Participants who received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve \[AUC\] at steady state from time zero to 168 hours after study drug administration).
Outcome measures
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=58 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=175 Participants
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=59 Participants
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of LY2189265 - Area Under the Concentration Time Curve (AUC)
|
14587 nanograms*hour/milliliter (ng*h/mL)
Standard Deviation 5674
|
7876 nanograms*hour/milliliter (ng*h/mL)
Standard Deviation 3064
|
4488 nanograms*hour/milliliter (ng*h/mL)
Standard Deviation 1746
|
—
|
Adverse Events
1.0/2.0 Milligram (mg) LY2189265
1.0/1.0 Milligram (mg) LY2189265
0.5/1.0 Milligram (mg) LY2189265
Placebo
Serious adverse events
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 participants at risk
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 participants at risk
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 participants at risk
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 participants at risk
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/65
|
0.00%
0/65
|
1.5%
1/66 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Pneumonia
|
1.5%
1/65 • Number of events 1
|
0.00%
0/65
|
0.00%
0/66
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Septic shock
|
0.00%
0/65
|
0.00%
0/65
|
0.00%
0/66
|
1.5%
1/66 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/65
|
1.5%
1/65 • Number of events 2
|
0.00%
0/66
|
0.00%
0/66
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/65
|
1.5%
1/65 • Number of events 1
|
0.00%
0/66
|
0.00%
0/66
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/65
|
0.00%
0/65
|
1.5%
1/66 • Number of events 1
|
0.00%
0/66
|
|
Respiratory, thoracic and mediastinal disorders
Cryptogenic organising pneumonia
|
0.00%
0/65
|
0.00%
0/65
|
1.5%
1/66 • Number of events 1
|
0.00%
0/66
|
Other adverse events
| Measure |
1.0/2.0 Milligram (mg) LY2189265
n=65 participants at risk
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 2.0 mg, SC injection, QW for 12 weeks
|
1.0/1.0 Milligram (mg) LY2189265
n=65 participants at risk
LY2189265: 1.0 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 16 weeks
|
0.5/1.0 Milligram (mg) LY2189265
n=66 participants at risk
LY2189265: 0.5 milligram (mg), subcutaneous (SC) injection, once weekly (QW) for 4 weeks; followed by 1.0 mg, SC injection, QW for 12 weeks
|
Placebo
n=66 participants at risk
Placebo: subcutaneous (SC), once weekly (QW) for 16 weeks
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
13.8%
9/65 • Number of events 9
|
7.7%
5/65 • Number of events 5
|
4.5%
3/66 • Number of events 3
|
6.1%
4/66 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain
|
6.2%
4/65 • Number of events 5
|
3.1%
2/65 • Number of events 2
|
7.6%
5/66 • Number of events 5
|
4.5%
3/66 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.2%
4/65 • Number of events 5
|
4.6%
3/65 • Number of events 3
|
3.0%
2/66 • Number of events 2
|
3.0%
2/66 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
9.2%
6/65 • Number of events 6
|
4.6%
3/65 • Number of events 3
|
9.1%
6/66 • Number of events 6
|
0.00%
0/66
|
|
Gastrointestinal disorders
Diarrhoea
|
13.8%
9/65 • Number of events 10
|
6.2%
4/65 • Number of events 4
|
7.6%
5/66 • Number of events 5
|
7.6%
5/66 • Number of events 9
|
|
Gastrointestinal disorders
Nausea
|
13.8%
9/65 • Number of events 10
|
16.9%
11/65 • Number of events 11
|
13.6%
9/66 • Number of events 13
|
7.6%
5/66 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
7/65 • Number of events 9
|
1.5%
1/65 • Number of events 1
|
4.5%
3/66 • Number of events 5
|
3.0%
2/66 • Number of events 2
|
|
General disorders
Chills
|
0.00%
0/65
|
0.00%
0/65
|
0.00%
0/66
|
4.5%
3/66 • Number of events 3
|
|
General disorders
Early satiety
|
0.00%
0/65
|
4.6%
3/65 • Number of events 3
|
1.5%
1/66 • Number of events 1
|
0.00%
0/66
|
|
Infections and infestations
Influenza
|
0.00%
0/65
|
3.1%
2/65 • Number of events 2
|
4.5%
3/66 • Number of events 3
|
0.00%
0/66
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
5/65 • Number of events 5
|
6.2%
4/65 • Number of events 4
|
3.0%
2/66 • Number of events 2
|
4.5%
3/66 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/65
|
0.00%
0/65
|
1.5%
1/66 • Number of events 1
|
6.1%
4/66 • Number of events 4
|
|
Infections and infestations
Urinary tract infection
|
3.1%
2/65 • Number of events 2
|
1.5%
1/65 • Number of events 1
|
4.5%
3/66 • Number of events 3
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/65
|
1.5%
1/65 • Number of events 1
|
4.5%
3/66 • Number of events 3
|
3.0%
2/66 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
4.6%
3/65 • Number of events 3
|
0.00%
0/65
|
4.5%
3/66 • Number of events 4
|
3.0%
2/66 • Number of events 2
|
|
Nervous system disorders
Headache
|
1.5%
1/65 • Number of events 3
|
4.6%
3/65 • Number of events 5
|
1.5%
1/66 • Number of events 1
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.5%
1/65 • Number of events 1
|
0.00%
0/65
|
3.0%
2/66 • Number of events 2
|
4.5%
3/66 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis seasonal
|
0.00%
0/65
|
0.00%
0/65
|
4.5%
3/66 • Number of events 3
|
0.00%
0/66
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60