Diabetes Mellitus, Type 2
Conditions
Brief summary
Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.
Interventions
DRUGLY2428757
14 mg subcutaneous injection 1 time a week for 5 weeks
DRUGTT223
subcutaneous injection once a day for 4 weeks
DRUGPlacebo for LY2428757
subcutaneous injection 1 time a week for 5 weeks
DRUGPlacebo for TT223
subcutaneous injection once a day for 4 weeks
Sponsors
OPKO Health, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Have type 2 diabetes mellitus (T2DM) for at least 6 months * Currently treated with diet and exercise alone or in combination with stable metformin * Glycosylated hemoglobin (HbA1c) 7.0% to 10.0% * Ages 18 to 70 years * Women not of childbearing potential * Body mass index (BMI) between 25 and 40 kilograms per meters squared (kg/m\^2), and stable weight in the 3 months prior to screening.
Exclusion criteria
* Use of diabetes medicine other than metformin in past 3 months * Gastrointestinal disease or surgery or drugs that significantly impacts gastric filling, emptying or motility; ongoing cholelithiasis or cholecystitis. * Chronic, daily proton pump inhibitors (PPIs) and histamine (H2) antagonists. * Severe hypoglycemia or hyperglycemia * Advanced microvascular diabetes complications * Medications to promote weight loss. * Breastfeeding women * Cardiac autonomic neuropathy * In the past 6 months have cardiac disease with functional status that is Class II-IV or a history of myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, transient ischemic attack, cerebrovascular accident (stroke), or decompensated congestive heart failure. * History of a supraventricular or ventricular tachycardia, pacemaker implantation, or other cardiac arrhythmia: Poorly controlled hypertension, malignant hypertension, renal artery stenosis, and/or evidence of labile blood pressure including symptomatic postural hypotension. * Electrocardiograms (ECG) abnormality or medication that impairs the ability to measure QT interval (QT), or correct the QT interval (QT) for rate. * QT interval Bazett corrected (QTcB) \>450 milliseconds (msec) or PR interval (PR) \>220 milliseconds (msec) * Personal or family history of long QT interval (QT) syndrome, sudden death, or unexplained syncope * Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase levels \> 2.5 times the upper limit of the reference range * Hypertriglyceridemia \> 400 mg/deciliter (dL) * Inadequately treated hypothyroidism or hyperthyroidism * Peptic ulcer disease and/or gastrointestinal bleeding/perforation. * Known pentagastrin hypersensitivity * Impaired renal function * Transplanted organ. * Active, uncontrolled endocrine or autoimmune abnormality * \> 2 weeks systemic glucocorticoid therapy * Ongoing courses of non-steroidal anti-inflammatory drugs (NSAIDs), except for aspirin 81-325 milligrams (mg) * Diagnosed malignancy or in remission for less than 5 years. * Prior acute or chronic pancreatitis or elevated serum lipase or amylase * Current central nervous system stimulant * Other conditions that preclude the participant from participating, following or completing the protocol. * Chronic infection * Personnel affiliated with the study and their immediate families. * Within 30 days of the initial dose of study drug, have participated in an interventional medical, surgical, or pharmaceutical study in which a medical or surgical treatment was given. * Have previously completed or withdrawn from this study after providing informed consent. * Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | Baseline (Week -1), 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | Baseline (Week -1), 3 weeks, 6 months | 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). |
| Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | Baseline (Week -1), 3 weeks, 6 months | 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). |
| 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 | Baseline (Week -1), 3 weeks, 6 months | 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). |
| Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | Baseline (Week -1), 3 weeks, 6 months | 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). |
| 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 | Baseline (Week -1), 3 weeks, 6 months | 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). |
| Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | Baseline (Week -1), 3 weeks, 6 months | 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). |
| Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | Baseline (Week -1), 4 weeks, 6 months | 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). |
| 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 | Baseline (Week -1), 6 months | 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). |
| 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 | Baseline (Week -1), Week 0, 3 weeks, 3.5 months, 6 months | 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). |
| 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 | Baseline (Week -1), 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months | 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). |
| Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | Baseline (Week -1), Week 0, 4 weeks, 6 months | 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). |
| Number of Participants With Antibodies to LY2428757 | Baseline (Week -1) through 6 months | Participants who were positive for antibodies to LY2428757. |
| Number of Participants With Antibodies to TT223 | Baseline (Week -1) through 6 months | Participants who were positive for antibodies for TT223. |
| Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs. |
| Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug. |
| Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Half-life is the time it takes for the concentration of drug in plasma to decline by 50%. |
| Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| 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) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | Baseline (Week -1), 4 weeks | 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). |
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs. |
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Half-life (t1/2) is the time it takes for the concentration of drug in plasma to decline by 50%. |
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity]) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | Baseline (Week -1), Week 0, 4 weeks, 6 months | 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). |
| 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) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | 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. |
| Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) | 0 (pre-dose) | 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. |
| Change From Baseline in Amylase at 6-Month Endpoint | Baseline (Week -1), 6 months | Change from baseline means the absolute change from baseline (endpoint-baseline). |
| Visual Analog Scale (VAS) for Nausea | 4 weeks, 6 months | 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. |
| Change From Baseline in Waist Circumference at 6-Month Endpoint | Baseline (Week -1), 6 months | Change from baseline means the absolute change from baseline (endpoint-baseline). |
| 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | Baseline (Week -1), 4 weeks, 6 months | 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. |
| Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Baseline (Week -1) through 6 months | 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. |
| Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Baseline (Week -1), 4 weeks, 6 months | 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). |
| Percentage of Participants With Hypoglycemia | Baseline (Week -1) through 6 months | 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. |
| Number of Participants With Hypoglycemia | Baseline (Week -1) through 6 months | 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). |
| Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | Baseline (Week -1) through 6 months | 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. |
| Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | Baseline (Week -1), 4 weeks, 6 months | 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). |
| Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | Baseline (Week -1), 3 weeks, 6 months | 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). |
| Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) | 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours | Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Reporting on 131 participants who received either TT223 or its placebo and reflects data from treatment and follow-up. 151 enrolled in run-in. 16/130 randomized to LY2428757 run-in did not get treatment assignment. 3/21 assigned to placebo run-in did not enter treatment phase. 1 was given treatment assignment but never received TT223 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| LY2428757 Plus TT223 3mg Weekly LY2428757 14 mg subcutaneous injection for 5 weeks plus TT223 3 mg subcutaneous injection daily for 4 weeks | 38 |
| LY2428757 Plus TT223 2mg Weekly LY2428757 14 mg subcutaneous injection for 5 weeks plus TT223 2 mg subcutaneous injection daily for 4 weeks | 37 |
| LY2428757 Plus TT223 Placebo Weekly LY2428757 14 mg subcutaneous injection for 5 weeks plus TT223 placebo subcutaneous injection daily for 4 weeks | 38 |
| LY Placebo Plus TT223 Placebo Weekly LY2428757 placebo subcutaneous injection for 5 weeks plus TT223 placebo subcutaneous injection daily for 4 weeks | 18 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 2 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 1 |
| Overall Study | Inclusion/Exclusion Criteria Not Met | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 3 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Sponsor Decision | 0 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | LY2428757 Plus TT223 3mg | LY2428757 Plus TT223 2mg | LY2428757 Plus TT223 Placebo | LY Placebo Plus TT223 Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 53.7 years STANDARD_DEVIATION 9.69 | 52.4 years STANDARD_DEVIATION 10.12 | 52.9 years STANDARD_DEVIATION 8.99 | 55.4 years STANDARD_DEVIATION 7.9 | 53.3 years STANDARD_DEVIATION 9.33 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 1 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 4 participants | 3 participants | 4 participants | 3 participants | 14 participants |
| Race/Ethnicity, Customized Not Assessed | 0 participants | 2 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized White | 32 participants | 31 participants | 33 participants | 12 participants | 108 participants |
| Region of Enrollment Puerto Rico | 1 participants | 3 participants | 5 participants | 1 participants | 10 participants |
| Region of Enrollment United States | 37 participants | 34 participants | 33 participants | 17 participants | 121 participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 16 Participants | 5 Participants | 55 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 22 Participants | 13 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 38 | 29 / 37 | 26 / 38 | 12 / 18 |
| serious Total, serious adverse events | 2 / 38 | 1 / 37 | 0 / 38 | 2 / 18 |
Outcome results
Primary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline glycosylated hemoglobin (HbA1c) value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | -0.08 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.163 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | 0.06 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.179 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | -0.15 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.162 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint | 0.04 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.234 |
p-value: 0.623Mixed Models Analysis
p-value: 0.809Mixed Models Analysis
Secondary
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
Population: Each visit includes participants who received at least 1 dose of TT223 or its placebo who had both a baseline value and a value at that visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 4 weeks (n=31, 22, 30, 15) | 152.75 milligrams per deciliter (mg/dL) | Standard Deviation 29.973 |
| LY2428757 Plus TT223 3mg | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 6 months (n=24, 19, 23, 12) | 173.18 milligrams per deciliter (mg/dL) | Standard Deviation 46.455 |
| LY2428757 Plus TT223 2mg | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 6 months (n=24, 19, 23, 12) | 177.50 milligrams per deciliter (mg/dL) | Standard Deviation 49.379 |
| LY2428757 Plus TT223 2mg | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 4 weeks (n=31, 22, 30, 15) | 147.10 milligrams per deciliter (mg/dL) | Standard Deviation 24.514 |
| LY2428757 Plus TT223 Placebo | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 4 weeks (n=31, 22, 30, 15) | 142.38 milligrams per deciliter (mg/dL) | Standard Deviation 32.199 |
| LY2428757 Plus TT223 Placebo | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 6 months (n=24, 19, 23, 12) | 176.33 milligrams per deciliter (mg/dL) | Standard Deviation 38.9 |
| LY Placebo Plus TT223 Placebo | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 4 weeks (n=31, 22, 30, 15) | 169.23 milligrams per deciliter (mg/dL) | Standard Deviation 55.866 |
| LY Placebo Plus TT223 Placebo | 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values | 6 months (n=24, 19, 23, 12) | 172.05 milligrams per deciliter (mg/dL) | Standard Deviation 28.688 |
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value for the variable being analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after midday meal 4 weeks (n=30,22,29,15) | -32.64 milligrams per deciliter (mg/dL) | Standard Error 6.719 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 4 weeks (n=31,22,30,15) | -24.30 milligrams per deciliter (mg/dL) | Standard Error 5.335 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after morning meal 4 weeks (n=30,21,29,15) | -38.41 milligrams per deciliter (mg/dL) | Standard Error 6.094 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 4 weeks (n=30,22,29,15) | -14.76 milligrams per deciliter (mg/dL) | Standard Error 5.95 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 4 weeks (n=31,22,30,15) | -29.28 milligrams per deciliter (mg/dL) | Standard Error 5.082 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 4 weeks (n=30,22,29,15) | -26.67 milligrams per deciliter (mg/dL) | Standard Error 5.565 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after evening meal 4 weeks (n=30,22,29,14) | -37.72 milligrams per deciliter (mg/dL) | Standard Error 6.728 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 4 weeks (n=28,21,28,15) | -35.44 milligrams per deciliter (mg/dL) | Standard Error 7.112 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 6 months (n=24,19,23,12) | -7.66 milligrams per deciliter (mg/dL) | Standard Error 7.693 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 6 months (n=24,19,23,12) | -5.00 milligrams per deciliter (mg/dL) | Standard Error 5.981 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after morning meal 6 months (n=23,19,23,12) | -12.25 milligrams per deciliter (mg/dL) | Standard Error 8.654 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 6 months (n=24,19,23,12) | -4.76 milligrams per deciliter (mg/dL) | Standard Error 8.345 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after midday meal 6 months (n=24,19,23,12) | -5.51 milligrams per deciliter (mg/dL) | Standard Error 9.418 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 6 months (n=24,19,23,12) | -2.61 milligrams per deciliter (mg/dL) | Standard Error 8.562 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after evening meal 6 months (n=24,19,23,12) | -11.20 milligrams per deciliter (mg/dL) | Standard Error 10.373 |
| LY2428757 Plus TT223 3mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 6 months (n=21,18,22,11) | -11.27 milligrams per deciliter (mg/dL) | Standard Error 9.684 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 4 weeks (n=30,22,29,15) | -28.36 milligrams per deciliter (mg/dL) | Standard Error 6.663 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 6 months (n=24,19,23,12) | -11.70 milligrams per deciliter (mg/dL) | Standard Error 8.759 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 6 months (n=21,18,22,11) | -21.61 milligrams per deciliter (mg/dL) | Standard Error 10.612 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 6 months (n=24,19,23,12) | 3.95 milligrams per deciliter (mg/dL) | Standard Error 9.452 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after evening meal 6 months (n=24,19,23,12) | -20.89 milligrams per deciliter (mg/dL) | Standard Error 11.815 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 6 months (n=24,19,23,12) | -4.89 milligrams per deciliter (mg/dL) | Standard Error 6.869 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after morning meal 4 weeks (n=30,21,29,15) | -63.72 milligrams per deciliter (mg/dL) | Standard Error 7.409 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after morning meal 6 months (n=23,19,23,12) | -18.40 milligrams per deciliter (mg/dL) | Standard Error 9.631 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after midday meal 4 weeks (n=30,22,29,15) | -38.90 milligrams per deciliter (mg/dL) | Standard Error 8.037 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after evening meal 4 weeks (n=30,22,29,14) | -53.39 milligrams per deciliter (mg/dL) | Standard Error 8.125 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 4 weeks (n=30,22,29,15) | -30.83 milligrams per deciliter (mg/dL) | Standard Error 7.088 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 4 weeks (n=31,22,30,15) | -42.95 milligrams per deciliter (mg/dL) | Standard Error 6.526 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after midday meal 6 months (n=24,19,23,12) | -4.15 milligrams per deciliter (mg/dL) | Standard Error 10.722 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 4 weeks (n=28,21,28,15) | -44.50 milligrams per deciliter (mg/dL) | Standard Error 8.378 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 6 months (n=24,19,23,12) | -7.53 milligrams per deciliter (mg/dL) | Standard Error 9.727 |
| LY2428757 Plus TT223 2mg | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 4 weeks (n=31,22,30,15) | -45.03 milligrams per deciliter (mg/dL) | Standard Error 6.192 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 4 weeks (n=30,22,29,15) | -30.87 milligrams per deciliter (mg/dL) | Standard Error 5.76 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after midday meal 4 weeks (n=30,22,29,15) | -39.30 milligrams per deciliter (mg/dL) | Standard Error 6.907 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 6 months (n=24,19,23,12) | 1.53 milligrams per deciliter (mg/dL) | Standard Error 8.881 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after evening meal 4 weeks (n=30,22,29,14) | -51.07 milligrams per deciliter (mg/dL) | Standard Error 6.927 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 4 weeks (n=28,21,28,15) | -41.22 milligrams per deciliter (mg/dL) | Standard Error 7.108 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 6 months (n=21,18,22,11) | -6.40 milligrams per deciliter (mg/dL) | Standard Error 9.599 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 6 months (n=24,19,23,12) | -5.76 milligrams per deciliter (mg/dL) | Standard Error 7.97 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 6 months (n=24,19,23,12) | -10.48 milligrams per deciliter (mg/dL) | Standard Error 6.236 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after evening meal 6 months (n=24,19,23,12) | -9.98 milligrams per deciliter (mg/dL) | Standard Error 10.726 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after morning meal 6 months (n=23,19,23,12) | -14.84 milligrams per deciliter (mg/dL) | Standard Error 8.739 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 6 months (n=24,19,23,12) | -0.96 milligrams per deciliter (mg/dL) | Standard Error 8.558 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 4 weeks (n=31,22,30,15) | -41.18 milligrams per deciliter (mg/dL) | Standard Error 5.215 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 4 weeks (n=31,22,30,15) | -32.41 milligrams per deciliter (mg/dL) | Standard Error 5.466 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after midday meal 6 months (n=24,19,23,12) | 4.67 milligrams per deciliter (mg/dL) | Standard Error 9.788 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after morning meal 4 weeks (n=30,21,29,15) | -51.70 milligrams per deciliter (mg/dL) | Standard Error 6.158 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 4 weeks (n=30,22,29,15) | -32.86 milligrams per deciliter (mg/dL) | Standard Error 6.048 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 6 months (n=21,18,22,11) | -3.79 milligrams per deciliter (mg/dL) | Standard Error 13.15 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Bedtime 4 weeks (n=28,21,28,15) | -14.66 milligrams per deciliter (mg/dL) | Standard Error 9.492 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after morning meal 4 weeks (n=30,21,29,15) | -23.80 milligrams per deciliter (mg/dL) | Standard Error 8.313 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 4 weeks (n=31,22,30,15) | -18.95 milligrams per deciliter (mg/dL) | Standard Error 7.136 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 6 months (n=24,19,23,12) | -15.57 milligrams per deciliter (mg/dL) | Standard Error 11.958 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after evening meal 4 weeks (n=30,22,29,14) | -29.01 milligrams per deciliter (mg/dL) | Standard Error 9.574 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after midday meal 6 months (n=24,19,23,12) | -12.71 milligrams per deciliter (mg/dL) | Standard Error 13.152 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 4 weeks (n=31,22,30,15) | -5.89 milligrams per deciliter (mg/dL) | Standard Error 7.529 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2 hours after midday meal 4 weeks (n=30,22,29,15) | -22.19 milligrams per deciliter (mg/dL) | Standard Error 9.328 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-morning meal fasting 6 months (n=24,19,23,12) | -6.45 milligrams per deciliter (mg/dL) | Standard Error 8.314 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-evening meal 4 weeks (n=30,22,29,15) | -16.85 milligrams per deciliter (mg/dL) | Standard Error 7.721 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after morning meal 6 months (n=23,19,23,12) | -27.48 milligrams per deciliter (mg/dL) | Standard Error 11.755 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | 2hours after evening meal 6 months (n=24,19,23,12) | -7.62 milligrams per deciliter (mg/dL) | Standard Error 14.491 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Average 6 months (n=24,19,23,12) | -13.07 milligrams per deciliter (mg/dL) | Standard Error 10.751 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 4 weeks (n=30,22,29,15) | -14.96 milligrams per deciliter (mg/dL) | Standard Error 8.194 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints | Pre-midday meal 6 months (n=24,19,23,12) | -9.54 milligrams per deciliter (mg/dL) | Standard Error 11.554 |
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline amylase value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Amylase at 6-Month Endpoint | -2.9 units/liter (U/L) | Standard Error 3.15 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Amylase at 6-Month Endpoint | -4.5 units/liter (U/L) | Standard Error 3.45 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Amylase at 6-Month Endpoint | 1.5 units/liter (U/L) | Standard Error 3.01 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Amylase at 6-Month Endpoint | -10.3 units/liter (U/L) | Standard Error 4.23 |
Secondary
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
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline fasting blood glucose (FBG) value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 4 weeks (n=32, 27, 33, 16) | -0.7 millimoles per liter (mmol/L) | Standard Error 0.4 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 6 months (n=23, 21, 22, 12) | 0.1 millimoles per liter (mmol/L) | Standard Error 0.41 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 6 months (n=23, 21, 22, 12) | 0.1 millimoles per liter (mmol/L) | Standard Error 0.44 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 4 weeks (n=32, 27, 33, 16) | -1.6 millimoles per liter (mmol/L) | Standard Error 0.44 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 4 weeks (n=32, 27, 33, 16) | -1.6 millimoles per liter (mmol/L) | Standard Error 0.4 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 6 months (n=23, 21, 22, 12) | 0.3 millimoles per liter (mmol/L) | Standard Error 0.42 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 4 weeks (n=32, 27, 33, 16) | 0.5 millimoles per liter (mmol/L) | Standard Error 0.56 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints | 6 months (n=23, 21, 22, 12) | -0.2 millimoles per liter (mmol/L) | Standard Error 0.57 |
Secondary
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
Population: Intent-to-treat: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline fasting insulin value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 4 weeks (n=31, 25, 32, 16) | 6.7 microinternational units/milliliter | Standard Error 4.57 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 6 months (n=23, 20, 22, 12) | 2.3 microinternational units/milliliter | Standard Error 4.03 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 6 months (n=23, 20, 22, 12) | -4.2 microinternational units/milliliter | Standard Error 4.41 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 4 weeks (n=31, 25, 32, 16) | -4.2 microinternational units/milliliter | Standard Error 4.89 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 4 weeks (n=31, 25, 32, 16) | 4.7 microinternational units/milliliter | Standard Error 4.49 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 6 months (n=23, 20, 22, 12) | 2.8 microinternational units/milliliter | Standard Error 3.95 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 4 weeks (n=31, 25, 32, 16) | 0.7 microinternational units/milliliter | Standard Error 6.21 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints | 6 months (n=23, 20, 22, 12) | -7.2 microinternational units/milliliter | Standard Error 5.43 |
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 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 | Baseline HbA1c <8% (n=24, 21, 23, 12) | -0.36 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.169 |
| LY2428757 Plus TT223 3mg | 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 | C-peptide level elevated (n=23, 21, 23, 12) | -0.30 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.254 |
| LY2428757 Plus TT223 3mg | 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 | BMI >=30 (n=24, 21, 23, 12) | -0.10 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.179 |
| LY2428757 Plus TT223 3mg | 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 | Baseline HbA1c >=8% (n=24, 21, 23, 12) | -0.17 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.25 |
| LY2428757 Plus TT223 3mg | 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 | BMI <30 (n=24, 21, 23, 12) | -0.45 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.194 |
| LY2428757 Plus TT223 3mg | 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 | HOMA <baseline median (n=23, 19, 20, 12) | -0.18 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.195 |
| LY2428757 Plus TT223 3mg | 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 | C-peptide level normal (n=23, 21, 23, 12) | -0.26 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.157 |
| LY2428757 Plus TT223 3mg | 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 | Duration of diabetes >=10 years (n=24, 21, 23, 12) | -0.19 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.278 |
| LY2428757 Plus TT223 3mg | 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 | Duration diabetes 3-<10 years (n=24, 21, 23, 12) | -0.19 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.157 |
| LY2428757 Plus TT223 3mg | 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 | HOMA >=baseline median (n=23, 19, 20, 12) | -0.24 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.187 |
| LY2428757 Plus TT223 3mg | 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 | Duration of diabetes <3 years (n=24, 21, 23, 12) | -0.87 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.348 |
| LY2428757 Plus TT223 2mg | 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 | HOMA >=baseline median (n=23, 19, 20, 12) | -0.15 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.188 |
| LY2428757 Plus TT223 2mg | 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 | Duration of diabetes <3 years (n=24, 21, 23, 12) | -0.77 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.236 |
| LY2428757 Plus TT223 2mg | 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 | BMI <30 (n=24, 21, 23, 12) | 0.37 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.25 |
| LY2428757 Plus TT223 2mg | 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 | BMI >=30 (n=24, 21, 23, 12) | -0.12 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.172 |
| LY2428757 Plus TT223 2mg | 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 | C-peptide level normal (n=23, 21, 23, 12) | 0.28 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.165 |
| LY2428757 Plus TT223 2mg | 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 | Duration of diabetes >=10 years (n=24, 21, 23, 12) | 0.09 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.349 |
| LY2428757 Plus TT223 2mg | 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 | C-peptide level elevated (n=23, 21, 23, 12) | -0.78 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.286 |
| LY2428757 Plus TT223 2mg | 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 | Duration diabetes 3-<10 years (n=24, 21, 23, 12) | 0.50 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.192 |
| LY2428757 Plus TT223 2mg | 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 | HOMA <baseline median (n=23, 19, 20, 12) | 0.28 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.241 |
| LY2428757 Plus TT223 2mg | 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 | Baseline HbA1c >=8% (n=24, 21, 23, 12) | 0.40 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.228 |
| LY2428757 Plus TT223 2mg | 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 | Baseline HbA1c <8% (n=24, 21, 23, 12) | -0.22 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.194 |
| LY2428757 Plus TT223 Placebo | 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 | Duration diabetes 3-<10 years (n=24, 21, 23, 12) | -0.34 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.172 |
| LY2428757 Plus TT223 Placebo | 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 | Baseline HbA1c <8% (n=24, 21, 23, 12) | -0.20 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.183 |
| LY2428757 Plus TT223 Placebo | 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 | Baseline HbA1c >=8% (n=24, 21, 23, 12) | -0.12 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.222 |
| LY2428757 Plus TT223 Placebo | 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 | C-peptide level normal (n=23, 21, 23, 12) | -0.20 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.14 |
| LY2428757 Plus TT223 Placebo | 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 | C-peptide level elevated (n=23, 21, 23, 12) | 0.06 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.6 |
| LY2428757 Plus TT223 Placebo | 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 | HOMA <baseline median (n=23, 19, 20, 12) | -0.23 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.209 |
| LY2428757 Plus TT223 Placebo | 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 | HOMA >=baseline median (n=23, 19, 20, 12) | -0.38 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.195 |
| LY2428757 Plus TT223 Placebo | 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 | BMI <30 (n=24, 21, 23, 12) | 0.07 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.194 |
| LY2428757 Plus TT223 Placebo | 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 | BMI >=30 (n=24, 21, 23, 12) | -0.45 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.189 |
| LY2428757 Plus TT223 Placebo | 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 | Duration of diabetes <3 years (n=24, 21, 23, 12) | 0.18 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.24 |
| LY2428757 Plus TT223 Placebo | 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 | Duration of diabetes >=10 years (n=24, 21, 23, 12) | -0.50 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.429 |
| LY Placebo Plus TT223 Placebo | 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 | HOMA >=baseline median (n=23, 19, 20, 12) | -0.56 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.322 |
| LY Placebo Plus TT223 Placebo | 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 | Duration of diabetes >=10 years (n=24, 21, 23, 12) | -0.28 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.425 |
| LY Placebo Plus TT223 Placebo | 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 | Duration of diabetes <3 years (n=24, 21, 23, 12) | -0.49 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.263 |
| LY Placebo Plus TT223 Placebo | 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 | HOMA <baseline median (n=23, 19, 20, 12) | 0.16 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.227 |
| LY Placebo Plus TT223 Placebo | 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 | C-peptide level elevated (n=23, 21, 23, 12) | -0.32 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.661 |
| LY Placebo Plus TT223 Placebo | 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 | C-peptide level normal (n=23, 21, 23, 12) | -0.05 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.195 |
| LY Placebo Plus TT223 Placebo | 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 | Duration diabetes 3-<10 years (n=24, 21, 23, 12) | 0.49 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.307 |
| LY Placebo Plus TT223 Placebo | 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 | Baseline HbA1c >=8% (n=24, 21, 23, 12) | 0.35 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.269 |
| LY Placebo Plus TT223 Placebo | 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 | Baseline HbA1c <8% (n=24, 21, 23, 12) | -0.53 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.274 |
| LY Placebo Plus TT223 Placebo | 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 | BMI >=30 (n=24, 21, 23, 12) | 0.03 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.229 |
| LY Placebo Plus TT223 Placebo | 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 | BMI <30 (n=24, 21, 23, 12) | -0.34 percent glucosylated hemoglobin (HbA1c) | Standard Error 0.335 |
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline glycosylated hemoglobin (HbA1c) value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | -0.81 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.111 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | -0.97 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.117 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | -0.79 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.112 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint | -0.19 percent glycosylated hemoglobin (HbA1c) | Standard Error 0.162 |
Secondary
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
Population: Intent-to-treat: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline HOMA value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 3 weeks (n=26, 23, 26, 14) | 19.12 units on a scale | Standard Error 7.605 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 6 months (n=19, 18, 19, 11) | -3.05 units on a scale | Standard Error 9.128 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 6 months (n=19, 18, 19, 11) | 4.41 units on a scale | Standard Error 9.415 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 3 weeks (n=26, 23, 26, 14) | 34.73 units on a scale | Standard Error 8.093 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 3 weeks (n=26, 23, 26, 14) | 37.76 units on a scale | Standard Error 7.597 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 6 months (n=19, 18, 19, 11) | 19.17 units on a scale | Standard Error 9.111 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 3 weeks (n=26, 23, 26, 14) | -14.99 units on a scale | Standard Error 10.193 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints | 6 months (n=19, 18, 19, 11) | -9.01 units on a scale | Standard Error 11.986 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 36, 38, 18) | 12.1 units per liter (U/L) | Standard Error 7.89 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=28, 23, 30, 15) | -2.1 units per liter (U/L) | Standard Error 4.52 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=32, 27, 34, 16) | 14.8 units per liter (U/L) | Standard Error 9.92 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 36, 38, 18) | 8.1 units per liter (U/L) | Standard Error 8.11 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=28, 23, 30, 15) | -5.0 units per liter (U/L) | Standard Error 4.95 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=32, 27, 34, 16) | 10.1 units per liter (U/L) | Standard Error 10.53 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=32, 27, 34, 16) | 40.5 units per liter (U/L) | Standard Error 9.79 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 36, 38, 18) | 15.8 units per liter (U/L) | Standard Error 7.89 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=28, 23, 30, 15) | 7.0 units per liter (U/L) | Standard Error 4.42 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 36, 38, 18) | 2.3 units per liter (U/L) | Standard Error 11.46 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=28, 23, 30, 15) | -3.1 units per liter (U/L) | Standard Error 6.34 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=32, 27, 34, 16) | 0.4 units per liter (U/L) | Standard Error 14.24 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline C-peptide area under the curve (AUC) value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 28, 32, 16) | 44.44 millimoles/liter*hour (mmol/L*hr) | Standard Error 163.317 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | 221.02 millimoles/liter*hour (mmol/L*hr) | Standard Error 185.341 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -148.34 millimoles/liter*hour (mmol/L*hr) | Standard Error 197.247 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 28, 32, 16) | -44.12 millimoles/liter*hour (mmol/L*hr) | Standard Error 176.487 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 28, 32, 16) | 119.23 millimoles/liter*hour (mmol/L*hr) | Standard Error 164.846 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -241.88 millimoles/liter*hour (mmol/L*hr) | Standard Error 190.87 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 28, 32, 16) | -24.89 millimoles/liter*hour (mmol/L*hr) | Standard Error 226.274 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -133.30 millimoles/liter*hour (mmol/L*hr) | Standard Error 253.264 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=30, 28, 32, 16) | -16.76 picomoles/liter (pmmol/L) | Standard Error 15.367 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -26.48 picomoles/liter (pmmol/L) | Standard Error 4.504 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -15.96 picomoles/liter (pmmol/L) | Standard Error 4.81 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=30, 28, 32, 16) | -29.12 picomoles/liter (pmmol/L) | Standard Error 15.888 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=30, 28, 32, 16) | -47.76 picomoles/liter (pmmol/L) | Standard Error 14.89 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -21.77 picomoles/liter (pmmol/L) | Standard Error 4.654 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=30, 28, 32, 16) | -26.46 picomoles/liter (pmmol/L) | Standard Error 21.164 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -12.10 picomoles/liter (pmmol/L) | Standard Error 6.156 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 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 | 3 Weeks (n=30, 28, 32, 16) | -0.90 picomoles/liter (pmmol/L) | Standard Error 2.007 |
| LY2428757 Plus TT223 3mg | 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 | 6 Months (n=23, 21, 22, 12) | 0.41 picomoles/liter (pmmol/L) | Standard Error 2.162 |
| LY2428757 Plus TT223 2mg | 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 | 6 Months (n=23, 21, 22, 12) | 0.51 picomoles/liter (pmmol/L) | Standard Error 2.302 |
| LY2428757 Plus TT223 2mg | 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 | 3 Weeks (n=30, 28, 32, 16) | 0.86 picomoles/liter (pmmol/L) | Standard Error 2.094 |
| LY2428757 Plus TT223 Placebo | 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 | 3 Weeks (n=30, 28, 32, 16) | 1.48 picomoles/liter (pmmol/L) | Standard Error 1.948 |
| LY2428757 Plus TT223 Placebo | 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 | 6 Months (n=23, 21, 22, 12) | -5.93 picomoles/liter (pmmol/L) | Standard Error 2.225 |
| LY Placebo Plus TT223 Placebo | 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 | 3 Weeks (n=30, 28, 32, 16) | -0.47 picomoles/liter (pmmol/L) | Standard Error 2.702 |
| LY Placebo Plus TT223 Placebo | 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 | 6 Months (n=23, 21, 22, 12) | 1.71 picomoles/liter (pmmol/L) | Standard Error 2.955 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline value and at least 1 post-baseline glucose area under the curve (AUC) value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 27, 32, 16) | 15.04 millimoles/liter*hour (mmol/L*hr) | Standard Error 2.121 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -1.21 millimoles/liter*hour (mmol/L*hr) | Standard Error 1.49 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -1.05 millimoles/liter*hour (mmol/L*hr) | Standard Error 1.622 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 27, 32, 16) | 13.14 millimoles/liter*hour (mmol/L*hr) | Standard Error 2.3 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 27, 32, 16) | 7.51 millimoles/liter*hour (mmol/L*hr) | Standard Error 2.138 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | -1.05 millimoles/liter*hour (mmol/L*hr) | Standard Error 1.549 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 3 Weeks (n=32, 27, 32, 16) | 28.47 millimoles/liter*hour (mmol/L*hr) | Standard Error 2.979 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints | 6 Months (n=23, 21, 22, 12) | 1.46 millimoles/liter*hour (mmol/L*hr) | Standard Error 2.036 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit and time point being assessed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 3 Weeks 2 hours (n=32, 27, 31, 16) | -1.48 millimoles/liter (mmol/L) | Standard Error 0.417 |
| LY2428757 Plus TT223 3mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 6 Months 2 hours (n=23, 21, 22, 12) | -0.72 millimoles/liter (mmol/L) | Standard Error 0.541 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 6 Months 2 hours (n=23, 21, 22, 12) | -0.06 millimoles/liter (mmol/L) | Standard Error 0.576 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 3 Weeks 2 hours (n=32, 27, 31, 16) | -1.12 millimoles/liter (mmol/L) | Standard Error 0.455 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 3 Weeks 2 hours (n=32, 27, 31, 16) | -2.90 millimoles/liter (mmol/L) | Standard Error 0.426 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 6 Months 2 hours (n=23, 21, 22, 12) | -0.43 millimoles/liter (mmol/L) | Standard Error 0.556 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 3 Weeks 2 hours (n=32, 27, 31, 16) | 0.60 millimoles/liter (mmol/L) | Standard Error 0.581 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints | 6 Months 2 hours (n=23, 21, 22, 12) | 0.58 millimoles/liter (mmol/L) | Standard Error 0.748 |
Secondary
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
Population: Intent-to-treat population (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline AUC insulin/AUC glucose value. Reporting is on the 131 participants who received either TT223 or its placebo and reflects data only from the treatment and follow-up phases of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 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 | 3 Weeks (n=30, 27, 32, 16) | -0.96 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.324 |
| LY2428757 Plus TT223 3mg | 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 | 6 Months (n=23, 21, 22, 12) | 0.05 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.413 |
| LY2428757 Plus TT223 2mg | 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 | 6 Months (n=23, 21, 22, 12) | -0.19 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.425 |
| LY2428757 Plus TT223 2mg | 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 | 3 Weeks (n=30, 27, 32, 16) | -0.90 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.341 |
| LY2428757 Plus TT223 Placebo | 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 | 3 Weeks (n=30, 27, 32, 16) | -0.16 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.321 |
| LY2428757 Plus TT223 Placebo | 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 | 6 Months (n=23, 21, 22, 12) | 0.15 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.418 |
| LY Placebo Plus TT223 Placebo | 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 | 3 Weeks (n=30, 27, 32, 16) | -1.37 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.433 |
| LY Placebo Plus TT223 Placebo | 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 | 6 Months (n=23, 21, 22, 12) | -0.53 millimoles/liter*hour (mmol/L*hr) | Standard Error 0.566 |
Secondary
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
Population: Because the subgroup analyses for MMTT response were not conducted due to the lack of statistically significant findings in the subgroup analysis for the HbA1c analyses, zero participants were analyzed.
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Change From Baseline in Waist Circumference at 6-Month Endpoint | 1.55 centimeters (cm) | Standard Deviation 5.276 |
| LY2428757 Plus TT223 2mg | Change From Baseline in Waist Circumference at 6-Month Endpoint | -0.60 centimeters (cm) | Standard Deviation 2.433 |
| LY2428757 Plus TT223 Placebo | Change From Baseline in Waist Circumference at 6-Month Endpoint | -0.16 centimeters (cm) | Standard Deviation 2.599 |
| LY Placebo Plus TT223 Placebo | Change From Baseline in Waist Circumference at 6-Month Endpoint | -0.33 centimeters (cm) | Standard Deviation 3.06 |
Secondary
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
Population: Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline weight value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 37, 38, 18) | -0.198 kilograms (kg) | Standard Error 0.238 |
| LY2428757 Plus TT223 3mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=24, 21, 23,12) | 0.066 kilograms (kg) | Standard Error 0.7007 |
| LY2428757 Plus TT223 3mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=33, 27, 33, 16) | -0.561 kilograms (kg) | Standard Error 0.2923 |
| LY2428757 Plus TT223 2mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 37, 38, 18) | -0.137 kilograms (kg) | Standard Error 0.2455 |
| LY2428757 Plus TT223 2mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=24, 21, 23,12) | 0.026 kilograms (kg) | Standard Error 0.7613 |
| LY2428757 Plus TT223 2mg | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=33, 27, 33, 16) | -0.975 kilograms (kg) | Standard Error 0.3167 |
| LY2428757 Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=33, 27, 33, 16) | -0.824 kilograms (kg) | Standard Error 0.2956 |
| LY2428757 Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 37, 38, 18) | -0.288 kilograms (kg) | Standard Error 0.2438 |
| LY2428757 Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=24, 21, 23,12) | -0.762 kilograms (kg) | Standard Error 0.7044 |
| LY Placebo Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | Week 0 (n=38, 37, 38, 18) | 0.305 kilograms (kg) | Standard Error 0.3338 |
| LY Placebo Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 6 months (n=24, 21, 23,12) | -0.164 kilograms (kg) | Standard Error 0.9996 |
| LY Placebo Plus TT223 Placebo | Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints | 4 weeks (n=33, 27, 33, 16) | -0.542 kilograms (kg) | Standard Error 0.409 |
Secondary
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
Population: All participants who received at least 1 dose of TT223 or its placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | 2 participants |
| LY2428757 Plus TT223 2mg | Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | 0 participants |
| LY2428757 Plus TT223 Placebo | Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | 0 participants |
| LY Placebo Plus TT223 Placebo | Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint | 1 participants |
Secondary
Number of Participants With Antibodies to LY2428757
Participants who were positive for antibodies to LY2428757.
Time frame: Baseline (Week -1) through 6 months
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Number of Participants With Antibodies to LY2428757 | 1 participants |
| LY2428757 Plus TT223 2mg | Number of Participants With Antibodies to LY2428757 | 1 participants |
| LY2428757 Plus TT223 Placebo | Number of Participants With Antibodies to LY2428757 | 0 participants |
| LY Placebo Plus TT223 Placebo | Number of Participants With Antibodies to LY2428757 | 0 participants |
Secondary
Number of Participants With Antibodies to TT223
Participants who were positive for antibodies for TT223.
Time frame: Baseline (Week -1) through 6 months
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Number of Participants With Antibodies to TT223 | 0 participants |
| LY2428757 Plus TT223 2mg | Number of Participants With Antibodies to TT223 | 0 participants |
| LY2428757 Plus TT223 Placebo | Number of Participants With Antibodies to TT223 | 0 participants |
| LY Placebo Plus TT223 Placebo | Number of Participants With Antibodies to TT223 | 0 participants |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Number of Participants With Hypoglycemia | 2 participants |
| LY2428757 Plus TT223 2mg | Number of Participants With Hypoglycemia | 2 participants |
| LY2428757 Plus TT223 Placebo | Number of Participants With Hypoglycemia | 3 participants |
| LY Placebo Plus TT223 Placebo | Number of Participants With Hypoglycemia | 1 participants |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Lipase >= 2 times the upper limit of normal | 0 percentage of participants |
| LY2428757 Plus TT223 3mg | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Amylase >=2 times the upper limit of normal | 0 percentage of participants |
| LY2428757 Plus TT223 2mg | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Amylase >=2 times the upper limit of normal | 0 percentage of participants |
| LY2428757 Plus TT223 2mg | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Lipase >= 2 times the upper limit of normal | 0 percentage of participants |
| LY2428757 Plus TT223 Placebo | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Lipase >= 2 times the upper limit of normal | 2 percentage of participants |
| LY2428757 Plus TT223 Placebo | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Amylase >=2 times the upper limit of normal | 0 percentage of participants |
| LY Placebo Plus TT223 Placebo | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Lipase >= 2 times the upper limit of normal | 0 percentage of participants |
| LY Placebo Plus TT223 Placebo | Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint | Amylase >=2 times the upper limit of normal | 0 percentage of participants |
Secondary
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
Population: Because the number of hypoglycemia events were too low to model the percentage of hypoglycemia, zero participants were analyzed.
Secondary
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)
Population: Analyses were not conducted due to insufficient time points being collected; zero participants were analyzed.
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 79.6 liters per hour (L/hr) | Geometric Coefficient of Variation 67 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 92.3 liters per hour (L/hr) | Geometric Coefficient of Variation 596 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 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) | Vz/F | 124 liters (L) | Geometric Coefficient of Variation 129 |
| LY2428757 Plus TT223 3mg | 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) | Vss/F | 163 liters (L) | Geometric Coefficient of Variation 97 |
| LY2428757 Plus TT223 2mg | 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) | Vz/F | 137 liters (L) | Geometric Coefficient of Variation 645 |
| LY2428757 Plus TT223 2mg | 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) | Vss/F | 202 liters (L) | Geometric Coefficient of Variation 519 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity]) | 25.1 nanograms*hour/milliliter (ng*hr/ml) | Geometric Coefficient of Variation 67 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity]) | 32.6 nanograms*hour/milliliter (ng*hr/ml) | Geometric Coefficient of Variation 596 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2) | 1.08 hours | Geometric Coefficient of Variation 59 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2) | 1.03 hours | Geometric Coefficient of Variation 52 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) | 5.61 nanograms per milliliter (ng/ml) | Geometric Coefficient of Variation 652 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) | 5.97 nanograms per milliliter (ng/ml) | Geometric Coefficient of Variation 1320 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax) | 0.50 hours |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax) | 0.50 hours |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 71.4 liters/hour (L/hr) | Geometric Coefficient of Variation 66 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) | 57.5 liters/hour (L/hr) | Geometric Coefficient of Variation 38 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | 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) | Vz/F | 115 liters (L) | Geometric Coefficient of Variation 108 |
| LY2428757 Plus TT223 3mg | 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) | Vss/F | 157 liters (L) | Geometric Coefficient of Variation 91 |
| LY2428757 Plus TT223 2mg | 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) | Vz/F | 99.2 liters (L) | Geometric Coefficient of Variation 87 |
| LY2428757 Plus TT223 2mg | 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) | Vss/F | 136 liters (L) | Geometric Coefficient of Variation 60 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity) | 28.0 nanograms*hour/milliliter (ng*hr/ml) | Geometric Coefficient of Variation 66 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity) | 52.2 nanograms*hour/milliliter (ng*hr/ml) | Geometric Coefficient of Variation 38 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis | 1.11 hours | Geometric Coefficient of Variation 56 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis | 1.20 hours | Geometric Coefficient of Variation 70 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax) | 8.52 nanograms per milliliter (ng/ml) | Geometric Coefficient of Variation 276 |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax) | 8.46 nanograms per milliliter (ng/ml) | Geometric Coefficient of Variation 531 |
Secondary
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
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LY2428757 Plus TT223 3mg | Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax) | 0.50 hours |
| LY2428757 Plus TT223 2mg | Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax) | 1.00 hours |
Secondary
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
Population: Each visit includes participants who received at least 1 dose of TT223 or its placebo who had both a baseline value and a value at that visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2428757 Plus TT223 3mg | Visual Analog Scale (VAS) for Nausea | 6 months (n=27, 24, 30, 15) | 7.1 units on a scale | Standard Deviation 11.31 |
| LY2428757 Plus TT223 3mg | Visual Analog Scale (VAS) for Nausea | 4 weeks (n=33, 27, 34, 16) | 22.0 units on a scale | Standard Deviation 20.49 |
| LY2428757 Plus TT223 3mg | Visual Analog Scale (VAS) for Nausea | Baseline (n=38, 37, 38, 18) | 10.8 units on a scale | Standard Deviation 19.21 |
| LY2428757 Plus TT223 2mg | Visual Analog Scale (VAS) for Nausea | 6 months (n=27, 24, 30, 15) | 3.4 units on a scale | Standard Deviation 4.86 |
| LY2428757 Plus TT223 2mg | Visual Analog Scale (VAS) for Nausea | 4 weeks (n=33, 27, 34, 16) | 27.6 units on a scale | Standard Deviation 26.67 |
| LY2428757 Plus TT223 2mg | Visual Analog Scale (VAS) for Nausea | Baseline (n=38, 37, 38, 18) | 5.7 units on a scale | Standard Deviation 11.27 |
| LY2428757 Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | 4 weeks (n=33, 27, 34, 16) | 11.9 units on a scale | Standard Deviation 19.66 |
| LY2428757 Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | Baseline (n=38, 37, 38, 18) | 8.4 units on a scale | Standard Deviation 17.12 |
| LY2428757 Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | 6 months (n=27, 24, 30, 15) | 7.3 units on a scale | Standard Deviation 18.38 |
| LY Placebo Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | 4 weeks (n=33, 27, 34, 16) | 9.1 units on a scale | Standard Deviation 11.92 |
| LY Placebo Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | 6 months (n=27, 24, 30, 15) | 8.1 units on a scale | Standard Deviation 12.99 |
| LY Placebo Plus TT223 Placebo | Visual Analog Scale (VAS) for Nausea | Baseline (n=38, 37, 38, 18) | 4.7 units on a scale | Standard Deviation 11.15 |