Diabetes Mellitus, Type 2
Conditions
Brief summary
A multicenter, multinational, randomized,double-blind, placebo-controlled study in patients with Type 2 Diabetes Mellitus (T2DM). Patients with inadequate glycemic control using diet and exercise alone, or in combination with metformin, will be enrolled. The primary objective of this study is to test the hypothesis that LY2428757 given to patients with T2DM inadequately controlled with diet and exercise alone, or metformin monotherapy, produces a significant decrease in the mean hemoglobin A1c (HbA1c) from baseline to endpoint at 12 weeks as compared to placebo. Trial consists of 12 weeks of double-blind treatment and 4-week safety follow-up.
Interventions
DRUGLY2428757
Once weekly for 12 weeks as a subcutaneous injection.
DRUGPlacebo
1 of 5 volumes of placebo given once weekly for 12 weeks as a subcutaneous injection.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes mellitus for at least 6 months prior to entering the trial. * Treated with diet and exercise alone or in combination with at least 1000 milligrams (mg)/day of metformin for at least 2 months prior to screening. * Have a glycosylated fraction of hemoglobin A (HbA1c) value of 7.0% - 10.0% at screening * Women of child-bearing potential must test negative for pregnancy at screening and agree to abstain from heterosexual intercourse for the duration of the study, or use 2 effective forms of birth control during the study. * Have a body mass index (BMI) between 25 and 40 kilograms per square meters kg/m\^2) at screening * Stable weight during the 3 months prior to screening.
Exclusion criteria
* Use any antidiabetic agent other than metformin during the 2 months prior to screening. * Have a gastrointestinal disease that significantly impacts gastric emptying or motility or have undergone bariatric surgery. * Are currently taking prescription or over-the counter medications to promote weight loss. * Have been previously diagnosed with pancreatitis * Women who are breastfeeding. * Have a history of myocardial infarction, unstable angina, coronary artery bypass graft (CABG), percutaneous coronary intervention, transient ischemic attack, stroke or decompensated congestive heart failure in the past 6 months. * Have poorly controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | baseline, 12 weeks | LSMean adjusted for baseline HbA1c, metformin use, treatment, visit, treatment-by-visit interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | baseline through 16 weeks | Blood samples were collected from all randomized participants to test for the development of antibodies binding to LY2428757. If a participant developed a positive anti-LY2428757 antibody titer, appropriate medical management was to be utilized at the discretion of the sponsor and investigator, if deemed necessary. |
| Total Average Concentration (Cavg) of LY2428757 | 4 weeks, 6 weeks, 8 weeks, 10 weeks | Average concentration (Cavg) is calculated as the AUC0-168 (area under the plasma concentration vs. time curve during one dosing interval of 168 hours) divided by 168 hours. The numbers presented reflect the average LY2428757 drug concentration circulating in the body over 168 hours (one dosing interval). |
| Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | baseline, 12 weeks | Self-monitored glucose levels measured at 7 timepoints during the day. Timepoints include: fasting pre-breakfast, 2 hours post breakfast, prior to lunch, 2 hours post lunch, prior to dinner, 2 hours post dinner, and prior to bed. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | baseline, 12 weeks | An oral glucose tolerance test (OGTT) was used to assess changes in glucose tolerance. The area under the plasma glucose concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for glucose represents the area that is under the curve of glucose values when they are plotted over time. Larger AUC values represent a greater average glucose value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | baseline, 12 weeks | An oral glucose tolerance test (OGTT) was used to assess changes in insulin secretory response. The area under the insulin concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for insulin represents the area that is under the curve of insulin values when they are plotted over time. Larger AUC values represent a greater average insulin value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | baseline, 12 weeks | An oral glucose tolerance test (OGTT) was used to assess changes in insulin secretory response. The area under the C-peptide concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for C-peptide represents the area that is under the curve of C-peptide values when they are plotted over time. Larger AUC values represent a greater average C-peptide value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | baseline, 12 weeks | The VAS scales for appetite (hunger) and satiety (how full) were recorded on a scale with range of possible scores from 0 to 100 represented in millimeters on a 10 centimeter line. For appetite, participant chooses where they think their appetite lies on a 10 centimeter line between two anchors (0 - not at all hungry and 10 - extremely hungry). For satiety, participant chooses where they think their satiety lies on a 10 centimeter line between two anchors (0 - not at all full and 10 - extremely full). LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in Fasting Weight From Baseline to Week 12 Endpoint | baseline, 12 weeks | LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction. |
| Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | baseline, 12 weeks | Impact of Weight on Quality of Life (IWQoL) - Lite Version consists of 31 items from 5 subscales: physical functioning, self-esteem, sexual life, public distress, and work as well as a total score. Individual item scoring ranges from 0 (never true) to 4 (always true) with total score range from 0 to 124. Higher scores on the subscales and total score correspond with lower levels of functioning or greater negative effect. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment. |
| Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | baseline, 12 weeks | DSC-R assesses the presence and perceived burden of diabetes-related symptoms using the following subscales: hypoglycemic, hyperglycemic, psychological, cardiovascular, neurological, ophthalmological. Participants evaluate symptoms based on a 5-point Likert-type scale, ranging from 1=not at all troublesome to 5=extremely troublesome. Higher scores indicated greater severity of symptoms within a domain, or poorer perceived health, respectively. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment. |
| Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | baseline, 12 weeks | Participant chooses where they think their current health state lies on a 10 centimeter line between two anchors (0 - worst imaginable health state and 10 - best imaginable health state). The possible range of scores is 0 to 100 and represents millimeters on the 10 centimeter line. A higher score is associated with better health state. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment. |
| Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Baseline, 12 Weeks | The EuroQoL Questionnaire - 5 Dimension (EQ-5D) is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each participant, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant. |
| Change in Fasting Lipids From Baseline to Week 12 Endpoint | baseline, 12 weeks | Fasting lipids were measured after overnight fasting of at least 8 hours. Lipids analyzed include triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total-cholesterol. LSMean adjusted for baseline and treatment. |
Countries
Austria, Germany, India, Mexico, Puerto Rico, Romania, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.5 mg LY2428757 Once weekly, subcutaneous injection of 0.5 mg LY2428757 for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 36 |
| 2.0 mg LY2428757 Once weekly, subcutaneous injection of 2.0 mg LY2428757 for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 43 |
| 6.2 mg LY2428757 Once weekly, subcutaneous injection of 6.2 mg LY2428757 for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 42 |
| 12.0 mg LY2428757 Once weekly, subcutaneous injection of 12.0 mg LY2428757 for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 42 |
| 17.6 mg LY2428757 Once weekly, subcutaneous injection of 17.6 mg LY2428757 for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 43 |
| Placebo Once weekly, subcutaneous injection of placebo for 12 weeks. All injections were administered by study site personnel who were blinded to treatment assignment. | 41 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 1 | 3 | 0 |
| Overall Study | Inclusion/Exclusion criteria not met | 0 | 2 | 0 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 | 3 | 5 | 3 |
Baseline characteristics
| Characteristic | Total | 2.0 mg LY2428757 | 6.2 mg LY2428757 | 12.0 mg LY2428757 | 17.6 mg LY2428757 | Placebo | 0.5 mg LY2428757 |
|---|---|---|---|---|---|---|---|
| Age Continuous | 55.2 years STANDARD_DEVIATION 8.93 | 54.6 years STANDARD_DEVIATION 8.33 | 56.4 years STANDARD_DEVIATION 8.07 | 55.2 years STANDARD_DEVIATION 9.78 | 54.0 years STANDARD_DEVIATION 9.45 | 56.3 years STANDARD_DEVIATION 9.88 | 54.5 years STANDARD_DEVIATION 8.06 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 15 participants | 4 participants | 1 participants | 4 participants | 1 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 7 participants | 1 participants | 3 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 47 participants | 6 participants | 8 participants | 6 participants | 10 participants | 8 participants | 9 participants |
| Race/Ethnicity, Customized Multiple Race | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 3 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 174 participants | 31 participants | 29 participants | 30 participants | 32 participants | 28 participants | 24 participants |
| Region of Enrollment Austria | 7 participants | 2 participants | 0 participants | 1 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Germany | 17 participants | 2 participants | 3 participants | 2 participants | 5 participants | 4 participants | 1 participants |
| Region of Enrollment Mexico | 17 participants | 4 participants | 1 participants | 4 participants | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Romania | 24 participants | 5 participants | 6 participants | 5 participants | 3 participants | 1 participants | 4 participants |
| Region of Enrollment South Africa | 49 participants | 8 participants | 10 participants | 6 participants | 8 participants | 7 participants | 10 participants |
| Region of Enrollment Spain | 4 participants | 0 participants | 1 participants | 1 participants | 2 participants | 0 participants | 0 participants |
| Region of Enrollment Ukraine | 34 participants | 4 participants | 9 participants | 5 participants | 7 participants | 5 participants | 4 participants |
| Region of Enrollment United Kingdom | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 93 participants | 17 participants | 12 participants | 18 participants | 16 participants | 19 participants | 11 participants |
| Sex: Female, Male Female | 123 Participants | 20 Participants | 24 Participants | 18 Participants | 22 Participants | 24 Participants | 15 Participants |
| Sex: Female, Male Male | 124 Participants | 23 Participants | 18 Participants | 24 Participants | 21 Participants | 17 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 36 | 25 / 42 | 26 / 42 | 24 / 41 | 28 / 43 | 23 / 40 |
| serious Total, serious adverse events | 1 / 36 | 4 / 42 | 1 / 42 | 1 / 41 | 0 / 43 | 0 / 40 |
Outcome results
Primary
Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint
LSMean adjusted for baseline HbA1c, metformin use, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg LY2428757 | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -0.60 percentage of glycosylated hemoglobin |
| 2.0 mg LY2428757 | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -0.80 percentage of glycosylated hemoglobin |
| 6.2 mg LY2428757 | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -1.24 percentage of glycosylated hemoglobin |
| 12.0 mg LY2428757 | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -1.41 percentage of glycosylated hemoglobin |
| 17.6 mg LY2428757 | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -1.37 percentage of glycosylated hemoglobin |
| Placebo | Change in Hemoglobin A1C (HbA1c) From Baseline to Week 12 Endpoint | -0.13 percentage of glycosylated hemoglobin |
p-value: 0.010995% CI: [-0.83, -0.11]Mixed Models Analysis
p-value: 0.000395% CI: [-1.02, -0.31]Mixed Models Analysis
p-value: <0.000195% CI: [-1.46, -0.76]Mixed Models Analysis
p-value: <0.000195% CI: [-1.64, -0.93]Mixed Models Analysis
p-value: <0.000195% CI: [-1.59, -0.88]Mixed Models Analysis
Secondary
Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint
Self-monitored glucose levels measured at 7 timepoints during the day. Timepoints include: fasting pre-breakfast, 2 hours post breakfast, prior to lunch, 2 hours post lunch, prior to dinner, 2 hours post dinner, and prior to bed. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | -12.33 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -13.35 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -17.71 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | -2.14 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | -24.25 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | -6.22 milligrams per deciliter (mg/dL) |
| 0.5 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -7.85 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | -7.92 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -32.25 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -23.79 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -22.63 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | -24.08 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | -17.08 milligrams per deciliter (mg/dL) |
| 2.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | -33.82 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -36.70 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | -38.10 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | -26.48 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | -25.42 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -45.02 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -44.43 milligrams per deciliter (mg/dL) |
| 6.2 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | -30.13 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -35.97 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | -22.09 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -45.58 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | -28.05 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | -39.90 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | -29.05 milligrams per deciliter (mg/dL) |
| 12.0 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -31.10 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | -32.85 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | -45.82 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -51.41 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | -41.48 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -54.77 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -53.91 milligrams per deciliter (mg/dL) |
| 17.6 mg LY2428757 | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | -26.37 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Fasting | 2.39 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Bed (n=27, 23, 33, 25, 29, 25) | 11.69 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Dinner (n=29, 28, 35, 29, 29, 29) | -1.51 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Lunch (n=28, 27, 35, 28, 30, 29) | -11.30 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Lunch (n=29, 27, 34, 28, 29, 28) | 13.98 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | Prior to Dinner (n=29, 27, 35, 28, 29, 29) | 0.45 milligrams per deciliter (mg/dL) |
| Placebo | Change in 7-Point Self-Monitored Glucose From Baseline to Week 12 Endpoint | 2 Hours Post Breakfast (n=29, 28, 34,28 30,29) | -2.53 milligrams per deciliter (mg/dL) |
p-value: 0.4848Mixed Models Analysis
p-value: 0.0029Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.6279Mixed Models Analysis
p-value: 0.0072Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.0335Mixed Models Analysis
p-value: 0.0221Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.0002Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.503Mixed Models Analysis
p-value: 0.1938Mixed Models Analysis
p-value: 0.0003Mixed Models Analysis
p-value: 0.0101Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.006Mixed Models Analysis
p-value: 0.0002Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.2468Mixed Models Analysis
p-value: 0.0413Mixed Models Analysis
p-value: 0.0004Mixed Models Analysis
p-value: 0.004Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: 0.0199Mixed Models Analysis
p-value: 0.0008Mixed Models Analysis
p-value: 0.0001Mixed Models Analysis
p-value: 0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
Secondary
Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint
An oral glucose tolerance test (OGTT) was used to assess changes in insulin secretory response. The area under the C-peptide concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for C-peptide represents the area that is under the curve of C-peptide values when they are plotted over time. Larger AUC values represent a greater average C-peptide value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg LY2428757 | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -683.72 picomole per minute per liter |
| 2.0 mg LY2428757 | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 31434.85 picomole per minute per liter |
| 6.2 mg LY2428757 | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 49370.53 picomole per minute per liter |
| 12.0 mg LY2428757 | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 46280.14 picomole per minute per liter |
| 17.6 mg LY2428757 | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 22012.58 picomole per minute per liter |
| Placebo | Change in C-peptide Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 8714.30 picomole per minute per liter |
Secondary
Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint
DSC-R assesses the presence and perceived burden of diabetes-related symptoms using the following subscales: hypoglycemic, hyperglycemic, psychological, cardiovascular, neurological, ophthalmological. Participants evaluate symptoms based on a 5-point Likert-type scale, ranging from 1=not at all troublesome to 5=extremely troublesome. Higher scores indicated greater severity of symptoms within a domain, or poorer perceived health, respectively. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement, last observation carried forward (LOCF) up to visit 9 (week 12)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg LY2428757 | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.3 units on a scale | Standard Error 0.3 |
| 2.0 mg LY2428757 | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.1 units on a scale | Standard Error 0.28 |
| 6.2 mg LY2428757 | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.9 units on a scale | Standard Error 0.28 |
| 12.0 mg LY2428757 | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.4 units on a scale | Standard Error 0.29 |
| 17.6 mg LY2428757 | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.3 units on a scale | Standard Error 0.29 |
| Placebo | Change in Diabetes Symptom Checklist-Revised (DSC-R) Average Score From Baseline to Week 12 Endpoint | -0.7 units on a scale | Standard Error 0.28 |
Secondary
Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint
Participant chooses where they think their current health state lies on a 10 centimeter line between two anchors (0 - worst imaginable health state and 10 - best imaginable health state). The possible range of scores is 0 to 100 and represents millimeters on the 10 centimeter line. A higher score is associated with better health state. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement, last observation carried forward (LOCF) up to visit 9 (week 12)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg LY2428757 | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 6.9 millimeters | Standard Error 2.59 |
| 2.0 mg LY2428757 | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 6.2 millimeters | Standard Error 2.33 |
| 6.2 mg LY2428757 | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 6.0 millimeters | Standard Error 2.41 |
| 12.0 mg LY2428757 | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 6.0 millimeters | Standard Error 2.46 |
| 17.6 mg LY2428757 | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 7.1 millimeters | Standard Error 2.47 |
| Placebo | Change in European Quality of Life (EuroQol)- Visual Analog Scale From Baseline to Week 12 Endpoint | 2.7 millimeters | Standard Error 2.48 |
Secondary
Change in Fasting Lipids From Baseline to Week 12 Endpoint
Fasting lipids were measured after overnight fasting of at least 8 hours. Lipids analyzed include triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total-cholesterol. LSMean adjusted for baseline and treatment.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement. The last post-baseline measurement was carried forward if the value at week 12 was missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | -0.10 millimole per liter (mmol/L) | Standard Error 0.104 |
| 0.5 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | 0.02 millimole per liter (mmol/L) | Standard Error 0.034 |
| 0.5 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | -0.15 millimole per liter (mmol/L) | Standard Error 0.139 |
| 0.5 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | 0.0 millimole per liter (mmol/L) | Standard Error 0.09 |
| 2.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | -0.1 millimole per liter (mmol/L) | Standard Error 0.09 |
| 2.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | 0.08 millimole per liter (mmol/L) | Standard Error 0.13 |
| 2.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | -0.01 millimole per liter (mmol/L) | Standard Error 0.1 |
| 2.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | -0.03 millimole per liter (mmol/L) | Standard Error 0.032 |
| 6.2 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | -0.35 millimole per liter (mmol/L) | Standard Error 0.13 |
| 6.2 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | -0.30 millimole per liter (mmol/L) | Standard Error 0.098 |
| 6.2 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | -0.03 millimole per liter (mmol/L) | Standard Error 0.032 |
| 6.2 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | -0.1 millimole per liter (mmol/L) | Standard Error 0.09 |
| 12.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | -0.10 millimole per liter (mmol/L) | Standard Error 0.112 |
| 12.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | -0.03 millimole per liter (mmol/L) | Standard Error 0.036 |
| 12.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | 0.0 millimole per liter (mmol/L) | Standard Error 0.1 |
| 12.0 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | -0.31 millimole per liter (mmol/L) | Standard Error 0.135 |
| 17.6 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | 0.02 millimole per liter (mmol/L) | Standard Error 0.032 |
| 17.6 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | -0.31 millimole per liter (mmol/L) | Standard Error 0.128 |
| 17.6 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | -0.1 millimole per liter (mmol/L) | Standard Error 0.09 |
| 17.6 mg LY2428757 | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | -0.25 millimole per liter (mmol/L) | Standard Error 0.099 |
| Placebo | Change in Fasting Lipids From Baseline to Week 12 Endpoint | HDL (n=35, 38, 39, 31, 39, 34) | 0.01 millimole per liter (mmol/L) | Standard Error 0.034 |
| Placebo | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Triglycerides (n=35, 40, 40, 37, 41, 37) | -0.22 millimole per liter (mmol/L) | Standard Error 0.135 |
| Placebo | Change in Fasting Lipids From Baseline to Week 12 Endpoint | Total cholesterol (n=35, 38, 39, 31, 39, 34) | 0.02 millimole per liter (mmol/L) | Standard Error 0.105 |
| Placebo | Change in Fasting Lipids From Baseline to Week 12 Endpoint | LDL (n=35, 37, 39, 31, 39, 34) | 0.1 millimole per liter (mmol/L) | Standard Error 0.09 |
p-value: 0.693ANCOVA
p-value: 0.104ANCOVA
p-value: 0.506ANCOVA
p-value: 0.648ANCOVA
p-value: 0.647ANCOVA
p-value: 0.781ANCOVA
p-value: 0.401ANCOVA
p-value: 0.464ANCOVA
p-value: 0.42ANCOVA
p-value: 0.762ANCOVA
p-value: 0.738ANCOVA
p-value: 0.277ANCOVA
p-value: 0.094ANCOVA
p-value: 0.792ANCOVA
p-value: 0.105ANCOVA
p-value: 0.403ANCOVA
p-value: 0.799ANCOVA
p-value: 0.029ANCOVA
p-value: 0.439ANCOVA
p-value: 0.062ANCOVA
Secondary
Change in Fasting Weight From Baseline to Week 12 Endpoint
LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg LY2428757 | Change in Fasting Weight From Baseline to Week 12 Endpoint | -0.75 kilograms (kg) |
| 2.0 mg LY2428757 | Change in Fasting Weight From Baseline to Week 12 Endpoint | -0.85 kilograms (kg) |
| 6.2 mg LY2428757 | Change in Fasting Weight From Baseline to Week 12 Endpoint | -2.12 kilograms (kg) |
| 12.0 mg LY2428757 | Change in Fasting Weight From Baseline to Week 12 Endpoint | -1.03 kilograms (kg) |
| 17.6 mg LY2428757 | Change in Fasting Weight From Baseline to Week 12 Endpoint | -2.60 kilograms (kg) |
| Placebo | Change in Fasting Weight From Baseline to Week 12 Endpoint | -0.59 kilograms (kg) |
p-value: 0.8003Mixed Models Analysis
p-value: 0.6736Mixed Models Analysis
p-value: 0.0123Mixed Models Analysis
p-value: 0.4771Mixed Models Analysis
p-value: 0.0013Mixed Models Analysis
Secondary
Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint
Impact of Weight on Quality of Life (IWQoL) - Lite Version consists of 31 items from 5 subscales: physical functioning, self-esteem, sexual life, public distress, and work as well as a total score. Individual item scoring ranges from 0 (never true) to 4 (always true) with total score range from 0 to 124. Higher scores on the subscales and total score correspond with lower levels of functioning or greater negative effect. LSMean adjusted for baseline, baseline HbA1c (less than 8.5% versus greater than or equal to 8.5%), metformin use, treatment.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement, last observation carried forward (LOCF) up to visit 9 (week 12)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg LY2428757 | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | 0.2 units on a scale | Standard Error 0.22 |
| 2.0 mg LY2428757 | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | -0.1 units on a scale | Standard Error 0.2 |
| 6.2 mg LY2428757 | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | 0.3 units on a scale | Standard Error 0.21 |
| 12.0 mg LY2428757 | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | 0.2 units on a scale | Standard Error 0.21 |
| 17.6 mg LY2428757 | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | 0.1 units on a scale | Standard Error 0.21 |
| Placebo | Change in Impact of Weight on Quality of Life - Lite (IWQoL-Lite) Average Score From Baseline to Week 12 Endpoint | 0.2 units on a scale | Standard Error 0.21 |
Secondary
Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint
An oral glucose tolerance test (OGTT) was used to assess changes in insulin secretory response. The area under the insulin concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for insulin represents the area that is under the curve of insulin values when they are plotted over time. Larger AUC values represent a greater average insulin value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg LY2428757 | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 3111.25 picomole per minute per liter |
| 2.0 mg LY2428757 | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 3984.37 picomole per minute per liter |
| 6.2 mg LY2428757 | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 12521.89 picomole per minute per liter |
| 12.0 mg LY2428757 | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 14179.28 picomole per minute per liter |
| 17.6 mg LY2428757 | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 8778.23 picomole per minute per liter |
| Placebo | Change in Insulin Total Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | 3540.52 picomole per minute per liter |
Secondary
Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint
An oral glucose tolerance test (OGTT) was used to assess changes in glucose tolerance. The area under the plasma glucose concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for glucose represents the area that is under the curve of glucose values when they are plotted over time. Larger AUC values represent a greater average glucose value over time. LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg LY2428757 | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -1370.49 milligrams per minute per deciliter |
| 2.0 mg LY2428757 | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -1709.67 milligrams per minute per deciliter |
| 6.2 mg LY2428757 | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -5786.59 milligrams per minute per deciliter |
| 12.0 mg LY2428757 | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -6354.83 milligrams per minute per deciliter |
| 17.6 mg LY2428757 | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -8025.33 milligrams per minute per deciliter |
| Placebo | Change in Total Glucose Area Under the Curve (AUC) From Baseline to Week 12 Endpoint | -238.64 milligrams per minute per deciliter |
p-value: 0.4193Mixed Models Analysis
p-value: 0.3026Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
p-value: <0.0001Mixed Models Analysis
Secondary
Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint
The VAS scales for appetite (hunger) and satiety (how full) were recorded on a scale with range of possible scores from 0 to 100 represented in millimeters on a 10 centimeter line. For appetite, participant chooses where they think their appetite lies on a 10 centimeter line between two anchors (0 - not at all hungry and 10 - extremely hungry). For satiety, participant chooses where they think their satiety lies on a 10 centimeter line between two anchors (0 - not at all full and 10 - extremely full). LSMean adjusted for baseline, treatment, visit, treatment-by-visit interaction.
Time frame: baseline, 12 weeks
Population: Modified intention to treat population, defined as all randomized participants with at least one post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -2.28 millimeters (mm) | Standard Error 3.05 |
| 0.5 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 13.32 millimeters (mm) | Standard Error 3.53 |
| 2.0 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -0.85 millimeters (mm) | Standard Error 3.03 |
| 2.0 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 3.04 millimeters (mm) | Standard Error 3.48 |
| 6.2 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -3.76 millimeters (mm) | Standard Error 2.88 |
| 6.2 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 5.98 millimeters (mm) | Standard Error 3.33 |
| 12.0 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -0.92 millimeters (mm) | Standard Error 3.04 |
| 12.0 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 2.38 millimeters (mm) | Standard Error 3.5 |
| 17.6 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 4.41 millimeters (mm) | Standard Error 3.44 |
| 17.6 mg LY2428757 | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -1.37 millimeters (mm) | Standard Error 3 |
| Placebo | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | Hunger | -4.22 millimeters (mm) | Standard Error 3.05 |
| Placebo | Change in Visual Analogue Scales (VAS) For Appetite and Satiety From Baseline to Week 12 Endpoint | How Full | 10.43 millimeters (mm) | Standard Error 3.49 |
p-value: 0.655Mixed Models Analysis
p-value: 0.436Mixed Models Analysis
p-value: 0.914Mixed Models Analysis
p-value: 0.446Mixed Models Analysis
p-value: 0.508Mixed Models Analysis
p-value: 0.561Mixed Models Analysis
p-value: 0.135Mixed Models Analysis
p-value: 0.357Mixed Models Analysis
p-value: 0.105Mixed Models Analysis
p-value: 0.221Mixed Models Analysis
Secondary
Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study
Blood samples were collected from all randomized participants to test for the development of antibodies binding to LY2428757. If a participant developed a positive anti-LY2428757 antibody titer, appropriate medical management was to be utilized at the discretion of the sponsor and investigator, if deemed necessary.
Time frame: baseline through 16 weeks
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.5 mg LY2428757 | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 1 participants |
| 2.0 mg LY2428757 | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 2 participants |
| 6.2 mg LY2428757 | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 1 participants |
| 12.0 mg LY2428757 | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 3 participants |
| 17.6 mg LY2428757 | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 2 participants |
| Placebo | Number of Participants With Detectable Antibodies To LY2428757 At Any Time During The Study | 1 participants |
Secondary
Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint
The EuroQoL Questionnaire - 5 Dimension (EQ-5D) is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each participant, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.
Time frame: Baseline, 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 94.3 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 97.2 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 68.6 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 66.7 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 60.0 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 61.1 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 94.3 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 88.9 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 91.4 percentage of participants |
| 0.5 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 80.6 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 77.8 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 73.8 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 97.6 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 97.2 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 81.0 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 88.9 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 59.5 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 52.8 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 64.3 percentage of participants |
| 2.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 69.4 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 100.0 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 70.0 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 76.2 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 83.3 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 90.5 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 90.0 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 90.0 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 73.8 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 87.5 percentage of participants |
| 6.2 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 54.8 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 59.0 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 63.9 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 77.8 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 77.8 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 74.4 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 84.6 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 91.7 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 87.2 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 94.4 percentage of participants |
| 12.0 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 94.9 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 54.8 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 100.0 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 81.0 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 97.1 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 81.0 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 71.4 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 74.3 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 66.7 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 95.2 percentage of participants |
| 17.6 mg LY2428757 | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 88.6 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Endpoint | 88.2 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Endpoint | 70.6 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Endpoint | 85.3 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care-Baseline | 97.5 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Usual Activities- Baseline | 75.0 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Baseline | 52.5 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Self Care- Endpoint | 97.1 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Pain/Discomfort- Endpoint | 61.8 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Mobility-Baseline | 75.0 percentage of participants |
| Placebo | Percent of Participants Domain Scores Indicating No Problems on European Quality of Life (EuroQol) at Baseline and Week 12 Endpoint | Anxiety/Depression- Baseline | 70.0 percentage of participants |
Secondary
Total Average Concentration (Cavg) of LY2428757
Average concentration (Cavg) is calculated as the AUC0-168 (area under the plasma concentration vs. time curve during one dosing interval of 168 hours) divided by 168 hours. The numbers presented reflect the average LY2428757 drug concentration circulating in the body over 168 hours (one dosing interval).
Time frame: 4 weeks, 6 weeks, 8 weeks, 10 weeks
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.5 mg LY2428757 | Total Average Concentration (Cavg) of LY2428757 | 29.5 nanograms per milliliter (ng/mL) |
| 2.0 mg LY2428757 | Total Average Concentration (Cavg) of LY2428757 | 118 nanograms per milliliter (ng/mL) |
| 6.2 mg LY2428757 | Total Average Concentration (Cavg) of LY2428757 | 453 nanograms per milliliter (ng/mL) |
| 12.0 mg LY2428757 | Total Average Concentration (Cavg) of LY2428757 | 877 nanograms per milliliter (ng/mL) |
| 17.6 mg LY2428757 | Total Average Concentration (Cavg) of LY2428757 | 1290 nanograms per milliliter (ng/mL) |
| Placebo | Total Average Concentration (Cavg) of LY2428757 | 0 nanograms per milliliter (ng/mL) |