A Phase 1 interventional study of LY2428757 and TT223 in Diabetes Mellitus, Type 2, sponsored by Eli Lilly and Company. Completed at 29 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2012-04-13.
Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Treatment
Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.
9,590 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 131 is above the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Eli Lilly and Company is the lead sponsor of 2,095 studies on the registry; 142 are open to participants now.
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Exclusion Criteria:
Weekly LY2428757 plus 3 milligrams (mg) daily TT223
Drug: LY2428757 · Drug: TT223
Weekly LY2428757 plus 2 mg daily TT223
Drug: LY2428757 · Drug: TT223
Weekly LY2428757 plus daily TT223 placebo
Drug: LY2428757 · Drug: Placebo for TT223
Weekly LY2428757 placebo plus daily TT223 placebo
Drug: Placebo for LY2428757 · Drug: Placebo for TT223
14 mg subcutaneous injection 1 time a week for 5 weeks
subcutaneous injection once a day for 4 weeks
subcutaneous injection 1 time a week for 5 weeks
subcutaneous injection once a day for 4 weeks
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 6 months
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 4 weeks
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Standardized mixed-meal tolerance test (MMTT) used to assess changes in function of cells that make insulin (pancreatic beta cell function). Area under the plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for glucose represents area under curve of values when plotted over time. Larger area under the curve values represent greater average glucose value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
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 area under the curve (AUC) of C-peptide values when plotted over time. Larger area under the curve (AUC) values represent a greater average C-peptide value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit interaction. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Mixed Meal Tolerance Test (MMTT) Response - Ratio of Insulin Area Under the Curve (AUC)/Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Mixed meal tolerance test (MMTT) to assess changes in function of cells making insulin. AUCinsulin/AUCglucose ratio: index of insulin secretion. Larger values reflect greater secretion adjusted for glucose in response to meal. Area under insulin concentration versus time curve and area under plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for insulin and glucose represents AUC of values plotted over time. LS means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under the plasma glucagon concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for glucagon represents the AUC of glucagon values when are plotted over time. Larger area under the curve (AUC) values represent a greater average glucagon value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon-like Peptide-1 (GLP-1) Area Under the Cure (AUC) at 3-Week and 6-Month Endpoints
Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under plasma glucagon-like peptide-1 (GLP-1) concentration versus time curve calculated using linear-trapezoidal method. Area under the curve (AUC) for glucagon-like peptide-1 (GLP-1) represents the AUC of GLP-1 values when plotted over time. Larger AUC values represent a greater average GLP-1 value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints
Standardized MMTT to assess changes in function of cells that make insulin (pancreatic beta cells). Glucose measured at 2-hour timepoint during MMTT reflects glucose values in response to meal. Change in postprandial glucose calculated based on difference of 2-hour postprandial glucose at endpoint compared to baseline. Larger changes from baseline represent a greater postprandial glucose compared to 2-hour timepoint prior to treatment. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline fasting blood glucose (FBG). Fasting blood glucose (FBG) is the mixed meal tolerance test (MMTT) glucose assessment at time point 0, where available, otherwise it is the assessment taken from the chemistry panel. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 4 weeks, 6 months
Change From Baseline in Glycosylated Hemoglobin (HbA1C) Adjusted for Baseline Glycosylated Hemoglobin (HbA1c), C-Peptide Level, Homeostasis Model Assessment of Insulin Resistance (HOMA), Duration of Diabetes, and Body Mass Index (BMI) at 6-Month Endpoint
HbA1c adjusted: baseline HbA1c (\<8%,≥8%); C-peptide level (normal, elevated); HOMA (\<baseline median,≥baseline median); duration diabetes (\<3,3-10,\>10 years); BMI (\<30,≥30). BMI estimates body fat based on weight/height squared. HOMA: index of function of cells that make insulin/insulin resistance. Indices derived from fasting glucose and insulin concentrations. LS means adjusted for treatment, baseline therapy, visit, treatment-by-visit, subgroup, subgroup-by-treatment, subgroup-by-visit, subgroup-by-treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 6 months
Change From Baseline in MMTT Response (Postprandial Glucose, Glucose AUC, Insulin/c-Peptide Secretory Response, HOMA, GLP-1, Glucagon) Adjusted for Baseline HbA1c, C-Peptide Level, HOMA, Duration of Diabetes, Weight at Week 0, 3, Month 3.5, 6 Endpoints
Subgroup analyses for mixed meal tolerance test (MMTT) response (adjusted for baseline glycosylated hemoglobin (HbA1c), C-peptide level, Homeostasis Model Assessment of Insulin Resistance (HOMA), duration of diabetes, weight) not performed due to lack of statistically significant findings in subgroup analysis for HbA1c analyses. HOMA was not done for mixed meal tolerance test (MMTT) because it is not calculated from the mixed meal tolerance test (MMTT). It is reported separately as a secondary outcome measure. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), Week 0, 3 weeks, 3.5 months, 6 months
Change From Baseline in Fasting Blood Glucose (FBG) Adjusted for Baseline HbA1c, C-Peptide Level, Homeostasis Model Assessment of Insulin Resistance, Duration of Diabetes, and Weight at 3-Week, 4-Week, 2-Month, 3.5-Month, 5-Month, and 6-Month Endpoints
The subgroup analyses for fasting blood glucose (FBG) (adjusted for baseline glycosylated hemoglobin \[HbA1c\]), C-peptide level, homeostasis model assessment of insulin resistance (HOMA), duration of diabetes, and weight) were not performed due to the lack of statistically significant findings in the subgroup analysis for the glycosylated hemoglobin (HbA1c) analyses. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months
Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline weight. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), Week 0, 4 weeks, 6 months
Number of Participants With Antibodies to LY2428757
Participants who were positive for antibodies to LY2428757.
Time frame: Baseline (Week -1) through 6 months
Number of Participants With Antibodies to TT223
Participants who were positive for antibodies for TT223.
Time frame: Baseline (Week -1) through 6 months
Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax)
Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax)
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis
Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity)
Area under the curve (AUC)(0-infinity) = area under concentration versus time from zero to infinity. Area under the curve (AUC) is a measure of the total exposure to a drug.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
Apparent total body clearance of drug calculated after extra-Vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, First Dose - Apparent Volume of Distribution During the Terminal Phase After Extra-Vascular Administration (Vz/F), Apparent Volume of Distribution at Steady-State After Extra-Vascular Administration (Vss/F)
volume of distribution during the terminal phase after extra-vascular administration (Vz/F): Apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-State after extra-vascular administration (Vss/F): Apparent volume that contains drug when drug is being given continuously.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax)
Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2)
Half-life (t1/2) is the time it takes for the concentration of drug in plasma to decline by 50%.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity])
Area under concentration versus time curve from zero to infinity (AUC\[0-infinity\]). Area under the curve (AUC) is a measure of the total exposure to a drug.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
Apparent total body clearance of drug calculated after extra-vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Volume of Distribution During the Terminal Phase After Extra-Vascular Administration (Vz/F), Apparent Volume of Distribution at Steady-State After Extra-Vascular Administration (Vss/F)
Apparent volume of distribution during the terminal phase after extra-vascular administration (Vz/F) is the apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-state after extra-vascular administration (Vss/F) is the apparent volume that contains drug when drug is being given continuously.
Time frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug. LY2428757 concentrations were collected at only a single timepoint; therefore, pharmacokinetic (PK) parameters could not be modeled from the data. Analysis was not done due to insufficient time points being collected.
Time frame: 0 (pre-dose)
Visual Analog Scale (VAS) for Nausea
The Visual Analog Scale (VAS) is a continuous measure for degree of nausea and/or gastrointestinal discomfort. Each of these scales is 100 millimeters (mm) in length with 0 meaning no nausea at all and 100 meaning extreme nausea. Participants record self-assessment of how much nausea they have had, from 0 to 100, during the time interval indicated.
Time frame: 4 weeks, 6 months
Change From Baseline in Waist Circumference at 6-Month Endpoint
Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 6 months
7-point Profile, Self-Monitored Blood Glucose (SMBG) Values
The 7-point average is the average of the mean value of all time points for the visit. Time points included pre-morning meal, 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and bedtime.
Time frame: Baseline (Week -1), 4 weeks, 6 months
Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints
7-point average=average of mean value of all time points for visit (premorning meal, 2-hours postmorning meal, premidday meal, 2-hours postmidday meal, preevening meal, 2-hours postevening meal, bedtime). Values represent mean of values collected same time on 3 separate days within week prior to visit. Values from repeated measures included fixed categorical effects: treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate baseline \<7-point average glucose value or time point presented. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 4 weeks, 6 months
Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline serum lipase. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), Week 0, 4 weeks, 6 months
Change From Baseline in Amylase at 6-Month Endpoint
Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 6 months
Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline amylase.
Time frame: Baseline (Week -1) through 6 months
Percentage of Participants With Hypoglycemia
Calculation of frequency of low glucose for time period. Hypoglycemia≥1 events: severe\<50mg/dL, unable to treat self/recover after treatment; documented symptomatic≤70mg/dL, adrenergic/neuroglycopenic symptoms; asymptomatic≤70mg/dL no symptoms; probable symptomatic glucose missing, adrenergic/neuroglycopenic symptoms; relative\>70mg/dL, adrenergic/neuroglycopenic symptoms, nocturnal≤70mg/dL, adrenergic/neuroglycopenic symptoms between bedtime/waking. Because number participants who experienced hypoglycemia was low for every arm (1-3/arm) did not model percentage participants with hypoglycemia.
Time frame: Baseline (Week -1) through 6 months
Number of Participants With Hypoglycemia
The number of participants for whom low blood glucose was reported. Hypoglycemia ≥1 events including: severe hypoglycemia(glucose \<50mg/dL, unable to treat self or recover after treatment); documented symptomatic (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms); asymptomatic (glucose ≤70mg/dL no symptoms); probable symptomatic (glucose missing, adrenergic or neuroglycopenic symptoms); relative (glucose \>70mg/dL, adrenergic or neuroglycopenic symptoms), nocturnal (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms between bedtime/waking).
Time frame: Baseline (Week -1) through 6 months
Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint
The protocol specified that deaths and nonfatal cardiovascular (CV) adverse events (AEs) be adjudicated by independent physician(s) with cardiology or neurology experience. The CV AEs to be adjudicated were protocol-defined as myocardial infarction (MI), hospitalization for unstable angina or for heart failure, coronary interventions (coronary artery bypass graft or percutaneous coronary intervention \[PCI\]) and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack (TIA). 3 CV events were adjudicated by an external independent adjudication committee.
Time frame: Baseline (Week -1) through 6 months
Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline Fasting Insulin. Fasting insulin is the Mixed-Meal Tolerance Test (MMTT) insulin assessment at timepoint 0, where available, otherwise it is the assessment taken from the fasting laboratory measurements obtained during the clinic visit. Change from baseline means the absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 4 weeks, 6 months
Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints
Values from repeated measures include fixed categorical effects of treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate of baseline HOMA derived beta-cell function (HOMA-B). HOMA=index of function of cells that make insulin. Indices derived from fasting glucose and insulin concentrations. HOMA is measurement reflecting fasting plasma glucose and insulin. Has no defined minimum/maximum value. HOMA-B values generated from table reflecting values derived from Oxford HOMA2 model calculator. Change from baseline=absolute change from baseline (endpoint-baseline).
Time frame: Baseline (Week -1), 3 weeks, 6 months
| Milestone | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Started | 38 | 37 | 38 | 18 |
| Completed | 28 | 24 | 30 | 15 |
| Not completed | 10 | 13 | 8 | 3 |
| Withdrew: Adverse event | 1 | 4 | 2 | 0 |
| Withdrew: Inclusion/exclusion criteria not met | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 | 3 | 0 |
| Withdrew: Death | 1 | 0 | 0 | 1 |
| Withdrew: Protocol violation | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 5 | 4 | 2 | 1 |
| Withdrew: Physician decision | 0 | 2 | 1 | 0 |
| Withdrew: Sponsor decision | 0 | 3 | 0 | 0 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).
| percent glycosylated hemoglobin (HbA1c) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | -0.08 ± 0.163 | 0.06 ± 0.179 | -0.15 ± 0.162 | 0.04 ± 0.234 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).
| percent glycosylated hemoglobin (HbA1c) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | -0.81 ± 0.111 | -0.97 ± 0.117 | -0.79 ± 0.112 | -0.19 ± 0.162 |
Standardized mixed-meal tolerance test (MMTT) used to assess changes in function of cells that make insulin (pancreatic beta cell function). Area under the plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for glucose represents area under curve of values when plotted over time. Larger area under the curve values represent greater average glucose value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| millimoles/liter*hour (mmol/L*hr) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks (n=32, 27, 32, 16) | 15.04 ± 2.121 | 13.14 ± 2.300 | 7.51 ± 2.138 | 28.47 ± 2.979 |
| 6 Months (n=23, 21, 22, 12) | -1.21 ± 1.490 | -1.05 ± 1.622 | -1.05 ± 1.549 | 1.46 ± 2.036 |
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 area under the curve (AUC) of C-peptide values when plotted over time. Larger area under the curve (AUC) values represent a greater average C-peptide value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit interaction. Change from baseline means the absolute change from baseline (endpoint-baseline).
| millimoles/liter*hour (mmol/L*hr) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks (n=32, 28, 32, 16) | 44.44 ± 163.317 | -44.12 ± 176.487 | 119.23 ± 164.846 | -24.89 ± 226.274 |
| 6 Months (n=23, 21, 22, 12) | 221.02 ± 185.341 | -148.34 ± 197.247 | -241.88 ± 190.870 | -133.30 ± 253.264 |
Mixed meal tolerance test (MMTT) to assess changes in function of cells making insulin. AUCinsulin/AUCglucose ratio: index of insulin secretion. Larger values reflect greater secretion adjusted for glucose in response to meal. Area under insulin concentration versus time curve and area under plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for insulin and glucose represents AUC of values plotted over time. LS means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| millimoles/liter*hour (mmol/L*hr) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks (n=30, 27, 32, 16) | -0.96 ± 0.324 | -0.90 ± 0.341 | -0.16 ± 0.321 | -1.37 ± 0.433 |
| 6 Months (n=23, 21, 22, 12) | 0.05 ± 0.413 | -0.19 ± 0.425 | 0.15 ± 0.418 | -0.53 ± 0.566 |
Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under the plasma glucagon concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for glucagon represents the AUC of glucagon values when are plotted over time. Larger area under the curve (AUC) values represent a greater average glucagon value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| picomoles/liter (pmmol/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks (n=30, 28, 32, 16) | -16.76 ± 15.367 | -29.12 ± 15.888 | -47.76 ± 14.890 | -26.46 ± 21.164 |
| 6 Months (n=23, 21, 22, 12) | -26.48 ± 4.504 | -15.96 ± 4.810 | -21.77 ± 4.654 | -12.10 ± 6.156 |
Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under plasma glucagon-like peptide-1 (GLP-1) concentration versus time curve calculated using linear-trapezoidal method. Area under the curve (AUC) for glucagon-like peptide-1 (GLP-1) represents the AUC of GLP-1 values when plotted over time. Larger AUC values represent a greater average GLP-1 value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| picomoles/liter (pmmol/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks (n=30, 28, 32, 16) | -0.90 ± 2.007 | 0.86 ± 2.094 | 1.48 ± 1.948 | -0.47 ± 2.702 |
| 6 Months (n=23, 21, 22, 12) | 0.41 ± 2.162 | 0.51 ± 2.302 | -5.93 ± 2.225 | 1.71 ± 2.955 |
Standardized MMTT to assess changes in function of cells that make insulin (pancreatic beta cells). Glucose measured at 2-hour timepoint during MMTT reflects glucose values in response to meal. Change in postprandial glucose calculated based on difference of 2-hour postprandial glucose at endpoint compared to baseline. Larger changes from baseline represent a greater postprandial glucose compared to 2-hour timepoint prior to treatment. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| millimoles/liter (mmol/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 Weeks 2 hours (n=32, 27, 31, 16) | -1.48 ± 0.417 | -1.12 ± 0.455 | -2.90 ± 0.426 | 0.60 ± 0.581 |
| 6 Months 2 hours (n=23, 21, 22, 12) | -0.72 ± 0.541 | -0.06 ± 0.576 | -0.43 ± 0.556 | 0.58 ± 0.748 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline fasting blood glucose (FBG). Fasting blood glucose (FBG) is the mixed meal tolerance test (MMTT) glucose assessment at time point 0, where available, otherwise it is the assessment taken from the chemistry panel. Change from baseline means the absolute change from baseline (endpoint-baseline).
| millimoles per liter (mmol/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 4 weeks (n=32, 27, 33, 16) | -0.7 ± 0.40 | -1.6 ± 0.44 | -1.6 ± 0.40 | 0.5 ± 0.56 |
| 6 months (n=23, 21, 22, 12) | 0.1 ± 0.41 | 0.1 ± 0.44 | 0.3 ± 0.42 | -0.2 ± 0.57 |
HbA1c adjusted: baseline HbA1c (\<8%,≥8%); C-peptide level (normal, elevated); HOMA (\<baseline median,≥baseline median); duration diabetes (\<3,3-10,\>10 years); BMI (\<30,≥30). BMI estimates body fat based on weight/height squared. HOMA: index of function of cells that make insulin/insulin resistance. Indices derived from fasting glucose and insulin concentrations. LS means adjusted for treatment, baseline therapy, visit, treatment-by-visit, subgroup, subgroup-by-treatment, subgroup-by-visit, subgroup-by-treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).
| percent glucosylated hemoglobin (HbA1c) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Baseline HbA1c <8% (n=24, 21, 23, 12) | -0.36 ± 0.169 | -0.22 ± 0.194 | -0.20 ± 0.183 | -0.53 ± 0.274 |
| Baseline HbA1c >=8% (n=24, 21, 23, 12) | -0.17 ± 0.250 | 0.40 ± 0.228 | -0.12 ± 0.222 | 0.35 ± 0.269 |
| C-peptide level normal (n=23, 21, 23, 12) | -0.26 ± 0.157 | 0.28 ± 0.165 | -0.20 ± 0.140 | -0.05 ± 0.195 |
| C-peptide level elevated (n=23, 21, 23, 12) | -0.30 ± 0.254 | -0.78 ± 0.286 | 0.06 ± 0.600 | -0.32 ± 0.661 |
| HOMA <baseline median (n=23, 19, 20, 12) | -0.18 ± 0.195 | 0.28 ± 0.241 | -0.23 ± 0.209 | 0.16 ± 0.227 |
| HOMA >=baseline median (n=23, 19, 20, 12) | -0.24 ± 0.187 | -0.15 ± 0.188 | -0.38 ± 0.195 | -0.56 ± 0.322 |
| BMI <30 (n=24, 21, 23, 12) | -0.45 ± 0.194 | 0.37 ± 0.250 | 0.07 ± 0.194 | -0.34 ± 0.335 |
| BMI >=30 (n=24, 21, 23, 12) | -0.10 ± 0.179 | -0.12 ± 0.172 | -0.45 ± 0.189 | 0.03 ± 0.229 |
| Duration of diabetes <3 years (n=24, 21, 23, 12) | -0.87 ± 0.348 | -0.77 ± 0.236 | 0.18 ± 0.240 | -0.49 ± 0.263 |
| Duration diabetes 3-<10 years (n=24, 21, 23, 12) | -0.19 ± 0.157 | 0.50 ± 0.192 | -0.34 ± 0.172 | 0.49 ± 0.307 |
| Duration of diabetes >=10 years (n=24, 21, 23, 12) | -0.19 ± 0.278 | 0.09 ± 0.349 | -0.50 ± 0.429 | -0.28 ± 0.425 |
Subgroup analyses for mixed meal tolerance test (MMTT) response (adjusted for baseline glycosylated hemoglobin (HbA1c), C-peptide level, Homeostasis Model Assessment of Insulin Resistance (HOMA), duration of diabetes, weight) not performed due to lack of statistically significant findings in subgroup analysis for HbA1c analyses. HOMA was not done for mixed meal tolerance test (MMTT) because it is not calculated from the mixed meal tolerance test (MMTT). It is reported separately as a secondary outcome measure. Change from baseline=absolute change from baseline (endpoint-baseline).
No measurements were reported for this outcome.
The subgroup analyses for fasting blood glucose (FBG) (adjusted for baseline glycosylated hemoglobin \[HbA1c\]), C-peptide level, homeostasis model assessment of insulin resistance (HOMA), duration of diabetes, and weight) were not performed due to the lack of statistically significant findings in the subgroup analysis for the glycosylated hemoglobin (HbA1c) analyses. Change from baseline means the absolute change from baseline (endpoint-baseline).
No measurements were reported for this outcome.
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline weight. Change from baseline means the absolute change from baseline (endpoint-baseline).
| kilograms (kg) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Week 0 (n=38, 37, 38, 18) | -0.198 ± 0.2380 | -0.137 ± 0.2455 | -0.288 ± 0.2438 | 0.305 ± 0.3338 |
| 4 weeks (n=33, 27, 33, 16) | -0.561 ± 0.2923 | -0.975 ± 0.3167 | -0.824 ± 0.2956 | -0.542 ± 0.4090 |
| 6 months (n=24, 21, 23,12) | 0.066 ± 0.7007 | 0.026 ± 0.7613 | -0.762 ± 0.7044 | -0.164 ± 0.9996 |
Participants who were positive for antibodies to LY2428757.
| participants | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Number of Participants With Antibodies to LY2428757 | 1 | 1 | 0 | 0 |
Participants who were positive for antibodies for TT223.
| participants | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Number of Participants With Antibodies to TT223 | 0 | 0 | 0 | 0 |
Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.
| hours | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax) | 0.50 ± 0.30-3.00 | 1.00 ± 0.30-4.00 |
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.
| nanograms per milliliter (ng/ml) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax) | 8.52 ± 276 | 8.46 ± 531 |
Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.
| hours | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis | 1.11 ± 56 | 1.20 ± 70 |
Area under the curve (AUC)(0-infinity) = area under concentration versus time from zero to infinity. Area under the curve (AUC) is a measure of the total exposure to a drug.
| nanograms*hour/milliliter (ng*hr/ml) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity) | 28.0 ± 66 | 52.2 ± 38 |
Apparent total body clearance of drug calculated after extra-Vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.
| liters/hour (L/hr) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 71.4 ± 66 | 57.5 ± 38 |
volume of distribution during the terminal phase after extra-vascular administration (Vz/F): Apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-State after extra-vascular administration (Vss/F): Apparent volume that contains drug when drug is being given continuously.
| liters (L) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Vz/F | 115 ± 108 | 99.2 ± 87 |
| Vss/F | 157 ± 91 | 136 ± 60 |
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.
| nanograms per milliliter (ng/ml) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) | 5.61 ± 652 | 5.97 ± 1320 |
Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.
| hours | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax) | 0.50 (0.33 to 6.00) | 0.50 (0.32 to 6.00) |
Half-life (t1/2) is the time it takes for the concentration of drug in plasma to decline by 50%.
| hours | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2) | 1.08 ± 59 | 1.03 ± 52 |
Area under concentration versus time curve from zero to infinity (AUC\[0-infinity\]). Area under the curve (AUC) is a measure of the total exposure to a drug.
| nanograms*hour/milliliter (ng*hr/ml) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity]) | 25.1 ± 67 | 32.6 ± 596 |
Apparent total body clearance of drug calculated after extra-vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.
| liters per hour (L/hr) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 79.6 ± 67 | 92.3 ± 596 |
Apparent volume of distribution during the terminal phase after extra-vascular administration (Vz/F) is the apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-state after extra-vascular administration (Vss/F) is the apparent volume that contains drug when drug is being given continuously.
| liters (L) | LY2428757 Plus TT223 2 mg | LY2428757 Plus TT223 3 mg |
|---|---|---|
| Vz/F | 124 ± 129 | 137 ± 645 |
| Vss/F | 163 ± 97 | 202 ± 519 |
Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug. LY2428757 concentrations were collected at only a single timepoint; therefore, pharmacokinetic (PK) parameters could not be modeled from the data. Analysis was not done due to insufficient time points being collected.
No measurements were reported for this outcome.
The Visual Analog Scale (VAS) is a continuous measure for degree of nausea and/or gastrointestinal discomfort. Each of these scales is 100 millimeters (mm) in length with 0 meaning no nausea at all and 100 meaning extreme nausea. Participants record self-assessment of how much nausea they have had, from 0 to 100, during the time interval indicated.
| units on a scale | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Baseline (n=38, 37, 38, 18) | 10.8 ± 19.21 | 5.7 ± 11.27 | 8.4 ± 17.12 | 4.7 ± 11.15 |
| 4 weeks (n=33, 27, 34, 16) | 22.0 ± 20.49 | 27.6 ± 26.67 | 11.9 ± 19.66 | 9.1 ± 11.92 |
| 6 months (n=27, 24, 30, 15) | 7.1 ± 11.31 | 3.4 ± 4.86 | 7.3 ± 18.38 | 8.1 ± 12.99 |
Change from baseline means the absolute change from baseline (endpoint-baseline).
| centimeters (cm) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Change From Baseline in Waist Circumference at 6-Month Endpoint | 1.55 ± 5.276 | -0.60 ± 2.433 | -0.16 ± 2.599 | -0.33 ± 3.060 |
The 7-point average is the average of the mean value of all time points for the visit. Time points included pre-morning meal, 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and bedtime.
| milligrams per deciliter (mg/dL) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 4 weeks (n=31, 22, 30, 15) | 152.75 ± 29.973 | 147.10 ± 24.514 | 142.38 ± 32.199 | 169.23 ± 55.866 |
| 6 months (n=24, 19, 23, 12) | 173.18 ± 46.455 | 177.50 ± 49.379 | 176.33 ± 38.900 | 172.05 ± 28.688 |
7-point average=average of mean value of all time points for visit (premorning meal, 2-hours postmorning meal, premidday meal, 2-hours postmidday meal, preevening meal, 2-hours postevening meal, bedtime). Values represent mean of values collected same time on 3 separate days within week prior to visit. Values from repeated measures included fixed categorical effects: treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate baseline \<7-point average glucose value or time point presented. Change from baseline=absolute change from baseline (endpoint-baseline).
| milligrams per deciliter (mg/dL) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Average 4 weeks (n=31,22,30,15) | -29.28 ± 5.082 | -45.03 ± 6.192 | -41.18 ± 5.215 | -18.95 ± 7.136 |
| Pre-morning meal fasting 4 weeks (n=31,22,30,15) | -24.30 ± 5.335 | -42.95 ± 6.526 | -32.41 ± 5.466 | -5.89 ± 7.529 |
| 2 hours after morning meal 4 weeks (n=30,21,29,15) | -38.41 ± 6.094 | -63.72 ± 7.409 | -51.70 ± 6.158 | -23.80 ± 8.313 |
| Pre-midday meal 4 weeks (n=30,22,29,15) | -14.76 ± 5.950 | -30.83 ± 7.088 | -32.86 ± 6.048 | -14.96 ± 8.194 |
| 2 hours after midday meal 4 weeks (n=30,22,29,15) | -32.64 ± 6.719 | -38.90 ± 8.037 | -39.30 ± 6.907 | -22.19 ± 9.328 |
| Pre-evening meal 4 weeks (n=30,22,29,15) | -26.67 ± 5.565 | -28.36 ± 6.663 | -30.87 ± 5.760 | -16.85 ± 7.721 |
| 2 hours after evening meal 4 weeks (n=30,22,29,14) | -37.72 ± 6.728 | -53.39 ± 8.125 | -51.07 ± 6.927 | -29.01 ± 9.574 |
| Bedtime 4 weeks (n=28,21,28,15) | -35.44 ± 7.112 | -44.50 ± 8.378 | -41.22 ± 7.108 | -14.66 ± 9.492 |
| Average 6 months (n=24,19,23,12) | -7.66 ± 7.693 | -11.70 ± 8.759 | -5.76 ± 7.970 | -13.07 ± 10.751 |
| Pre-morning meal fasting 6 months (n=24,19,23,12) | -5.00 ± 5.981 | -4.89 ± 6.869 | -10.48 ± 6.236 | -6.45 ± 8.314 |
| 2hours after morning meal 6 months (n=23,19,23,12) | -12.25 ± 8.654 | -18.40 ± 9.631 | -14.84 ± 8.739 | -27.48 ± 11.755 |
| Pre-midday meal 6 months (n=24,19,23,12) | -4.76 ± 8.345 | 3.95 ± 9.452 | -0.96 ± 8.558 | -9.54 ± 11.554 |
| 2hours after midday meal 6 months (n=24,19,23,12) | -5.51 ± 9.418 | -4.15 ± 10.722 | 4.67 ± 9.788 | -12.71 ± 13.152 |
| Pre-evening meal 6 months (n=24,19,23,12) | -2.61 ± 8.562 | -7.53 ± 9.727 | 1.53 ± 8.881 | -15.57 ± 11.958 |
| 2hours after evening meal 6 months (n=24,19,23,12) | -11.20 ± 10.373 | -20.89 ± 11.815 | -9.98 ± 10.726 | -7.62 ± 14.491 |
| Bedtime 6 months (n=21,18,22,11) | -11.27 ± 9.684 | -21.61 ± 10.612 | -6.40 ± 9.599 | -3.79 ± 13.150 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline serum lipase. Change from baseline means the absolute change from baseline (endpoint-baseline).
| units per liter (U/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Week 0 (n=38, 36, 38, 18) | 12.1 ± 7.89 | 8.1 ± 8.11 | 15.8 ± 7.89 | 2.3 ± 11.46 |
| 4 weeks (n=32, 27, 34, 16) | 14.8 ± 9.92 | 10.1 ± 10.53 | 40.5 ± 9.79 | 0.4 ± 14.24 |
| 6 months (n=28, 23, 30, 15) | -2.1 ± 4.52 | -5.0 ± 4.95 | 7.0 ± 4.42 | -3.1 ± 6.34 |
Change from baseline means the absolute change from baseline (endpoint-baseline).
| units/liter (U/L) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Change From Baseline in Amylase at 6-Month Endpoint | -2.9 ± 3.15 | -4.5 ± 3.45 | 1.5 ± 3.01 | -10.3 ± 4.23 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline amylase.
| percentage of participants | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Lipase >= 2 times the upper limit of normal | 0 | 0 | 2 | 0 |
| Amylase >=2 times the upper limit of normal | 0 | 0 | 0 | 0 |
Calculation of frequency of low glucose for time period. Hypoglycemia≥1 events: severe\<50mg/dL, unable to treat self/recover after treatment; documented symptomatic≤70mg/dL, adrenergic/neuroglycopenic symptoms; asymptomatic≤70mg/dL no symptoms; probable symptomatic glucose missing, adrenergic/neuroglycopenic symptoms; relative\>70mg/dL, adrenergic/neuroglycopenic symptoms, nocturnal≤70mg/dL, adrenergic/neuroglycopenic symptoms between bedtime/waking. Because number participants who experienced hypoglycemia was low for every arm (1-3/arm) did not model percentage participants with hypoglycemia.
No measurements were reported for this outcome.
The number of participants for whom low blood glucose was reported. Hypoglycemia ≥1 events including: severe hypoglycemia(glucose \<50mg/dL, unable to treat self or recover after treatment); documented symptomatic (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms); asymptomatic (glucose ≤70mg/dL no symptoms); probable symptomatic (glucose missing, adrenergic or neuroglycopenic symptoms); relative (glucose \>70mg/dL, adrenergic or neuroglycopenic symptoms), nocturnal (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms between bedtime/waking).
| participants | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Number of Participants With Hypoglycemia | 2 | 2 | 3 | 1 |
The protocol specified that deaths and nonfatal cardiovascular (CV) adverse events (AEs) be adjudicated by independent physician(s) with cardiology or neurology experience. The CV AEs to be adjudicated were protocol-defined as myocardial infarction (MI), hospitalization for unstable angina or for heart failure, coronary interventions (coronary artery bypass graft or percutaneous coronary intervention \[PCI\]) and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack (TIA). 3 CV events were adjudicated by an external independent adjudication committee.
| participants | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | 2 | 0 | 0 | 1 |
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline Fasting Insulin. Fasting insulin is the Mixed-Meal Tolerance Test (MMTT) insulin assessment at timepoint 0, where available, otherwise it is the assessment taken from the fasting laboratory measurements obtained during the clinic visit. Change from baseline means the absolute change from baseline (endpoint-baseline).
| microinternational units/milliliter | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 4 weeks (n=31, 25, 32, 16) | 6.7 ± 4.57 | -4.2 ± 4.89 | 4.7 ± 4.49 | 0.7 ± 6.21 |
| 6 months (n=23, 20, 22, 12) | 2.3 ± 4.03 | -4.2 ± 4.41 | 2.8 ± 3.95 | -7.2 ± 5.43 |
Values from repeated measures include fixed categorical effects of treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate of baseline HOMA derived beta-cell function (HOMA-B). HOMA=index of function of cells that make insulin. Indices derived from fasting glucose and insulin concentrations. HOMA is measurement reflecting fasting plasma glucose and insulin. Has no defined minimum/maximum value. HOMA-B values generated from table reflecting values derived from Oxford HOMA2 model calculator. Change from baseline=absolute change from baseline (endpoint-baseline).
| units on a scale | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| 3 weeks (n=26, 23, 26, 14) | 19.12 ± 7.605 | 34.73 ± 8.093 | 37.76 ± 7.597 | -14.99 ± 10.193 |
| 6 months (n=19, 18, 19, 11) | -3.05 ± 9.128 | 4.41 ± 9.415 | 19.17 ± 9.111 | -9.01 ± 11.986 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | — | 2/38 (5.3%) | 23/38 (60.5%) |
| LY2428757 Plus TT223 2mg | — | 1/37 (2.7%) | 29/37 (78.4%) |
| LY2428757 Plus TT223 Placebo | — | 0/38 (0%) | 26/38 (68.4%) |
| LY Placebo Plus TT223 Placebo | — | 2/18 (11.1%) | 12/18 (66.7%) |
| Event | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| Acute myocardial infarctionCardiac disorders | 0/38 | 0/37 | 0/38 | 1/18 |
| Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/38 | 0/37 | 0/38 | 1/18 |
| Carotid artery stenosisNervous system disorders | 0/38 | 1/37 | 0/38 | 0/18 |
| Ischaemic cardiomyopathyCardiac disorders | 1/38 | 0/37 | 0/38 | 0/18 |
| Gun shot woundInjury, poisoning and procedural complications | 1/38 | 0/37 | 0/38 | 0/18 |
| Event | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo |
|---|---|---|---|---|
| NauseaGastrointestinal disorders | 11/38 | 15/37 | 5/38 | 1/18 |
| VomitingGastrointestinal disorders | 6/38 | 5/37 | 1/38 | 0/18 |
| DizzinessNervous system disorders | 5/38 | 2/37 | 1/38 | 0/18 |
| InfluenzaInfections and infestations | 0/38 | 2/37 | 3/38 | 2/18 |
| Decreased appetiteMetabolism and nutrition disorders | 2/38 | 2/37 | 3/38 | 2/18 |
| FatigueGeneral disorders | 0/38 | 4/37 | 0/38 | 0/18 |
| DiarrhoeaGastrointestinal disorders | 1/38 | 3/37 | 2/38 | 1/18 |
| DyspepsiaGastrointestinal disorders | 2/38 | 3/37 | 1/38 | 0/18 |
| Upper respiratory tract infectionInfections and infestations | 0/38 | 3/37 | 2/38 | 1/18 |
| HyperglycaemiaMetabolism and nutrition disorders | 3/38 | 0/37 | 1/38 | 0/18 |
| Age Continuous(years) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo | Total |
|---|---|---|---|---|---|
| Mean | 53.7 ± 9.69 | 52.4 ± 10.12 | 52.9 ± 8.99 | 55.4 ± 7.90 | 53.3 ± 9.33 |
| Sex: Female, Male(Participants) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo | Total |
|---|---|---|---|---|---|
| Female | 17 | 17 | 16 | 5 | 55 |
| Male | 21 | 20 | 22 | 13 | 76 |
| Race/Ethnicity, Customized(participants) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo | Total |
|---|---|---|---|---|---|
| American Indian or Alaskan Native | 0 | 1 | 0 | 1 | 2 |
| Asian | 2 | 0 | 1 | 1 | 4 |
| Black or African American | 4 | 3 | 4 | 3 | 14 |
| White | 32 | 31 | 33 | 12 | 108 |
| Not Assessed | 0 | 2 | 0 | 1 | 3 |
| Region of Enrollment(participants) | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo | Total |
|---|---|---|---|---|---|
| United States | 37 | 34 | 33 | 17 | 121 |
| Puerto Rico | 1 | 3 | 5 | 1 | 10 |
This study is completed, as verified in Mar 2012. You cannot join it, but the record below documents what was studied.
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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.