Back to resultsA Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY2428757
TT223
Placebo for LY2428757
Placebo for TT223
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2
Eligibility Criteria
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.
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
LY2428757 plus TT223 3 milligrams (mg)
LY2428757 plus TT223 2mg
LY2428757 plus placebo
Placebo plus Placebo
Arm Description
Weekly LY2428757 plus 3 milligrams (mg) daily TT223
Weekly LY2428757 plus 2 mg daily TT223
Weekly LY2428757 plus daily TT223 placebo
Weekly LY2428757 placebo plus daily TT223 placebo
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Number of Participants With Antibodies to LY2428757
Participants who were positive for antibodies to LY2428757.
Number of Participants With Antibodies to TT223
Participants who were positive for antibodies for TT223.
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.
Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax)
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
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)
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)
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)
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.
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.
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.
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%.
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.
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.
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.
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.
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.
Change From Baseline in Waist Circumference at 6-Month Endpoint
Change from baseline means the absolute change from baseline (endpoint-baseline).
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.
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).
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).
Change From Baseline in Amylase at 6-Month Endpoint
Change from baseline means the absolute change from baseline (endpoint-baseline).
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.
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.
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).
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.
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).
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).
Full Information
NCT ID
NCT00853151
First Posted
February 26, 2009
Last Updated
March 19, 2012
Sponsor
Eli Lilly and Company
Collaborators
OPKO Health, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00853151
Brief Title
A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes
Official Title
A Proof of Concept Study to Evaluate the Coadministration of TT223 Given Daily and LY2428757 Given Once-Weekly for Four Weeks in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
OPKO Health, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
131 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY2428757 plus TT223 3 milligrams (mg)
Arm Type
Experimental
Arm Description
Weekly LY2428757 plus 3 milligrams (mg) daily TT223
Arm Title
LY2428757 plus TT223 2mg
Arm Type
Experimental
Arm Description
Weekly LY2428757 plus 2 mg daily TT223
Arm Title
LY2428757 plus placebo
Arm Type
Experimental
Arm Description
Weekly LY2428757 plus daily TT223 placebo
Arm Title
Placebo plus Placebo
Arm Type
Placebo Comparator
Arm Description
Weekly LY2428757 placebo plus daily TT223 placebo
Intervention Type
Drug
Intervention Name(s)
LY2428757
Intervention Description
14 mg subcutaneous injection 1 time a week for 5 weeks
Intervention Type
Drug
Intervention Name(s)
TT223
Intervention Description
subcutaneous injection once a day for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo for LY2428757
Intervention Description
subcutaneous injection 1 time a week for 5 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo for TT223
Intervention Description
subcutaneous injection once a day for 4 weeks
Primary Outcome Measure Information:
Title
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint
Description
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
Title
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Description
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
Title
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Description
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
Title
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
Description
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
Title
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
Description
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
Title
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
Description
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
Title
Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints
Description
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
Title
Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints
Description
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
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Title
Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints
Description
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
Title
Number of Participants With Antibodies to LY2428757
Description
Participants who were positive for antibodies to LY2428757.
Time Frame
Baseline (Week -1) through 6 months
Title
Number of Participants With Antibodies to TT223
Description
Participants who were positive for antibodies for TT223.
Time Frame
Baseline (Week -1) through 6 months
Title
Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax)
Description
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
Title
Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax)
Description
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
Title
Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis
Description
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
Title
Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity)
Description
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
Title
Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
Description
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
Title
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)
Description
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
Title
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
Description
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
Title
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax)
Description
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
Title
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2)
Description
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
Title
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity])
Description
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
Title
Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
Description
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
Title
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)
Description
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
Title
Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
Description
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)
Title
Visual Analog Scale (VAS) for Nausea
Description
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
Title
Change From Baseline in Waist Circumference at 6-Month Endpoint
Description
Change from baseline means the absolute change from baseline (endpoint-baseline).
Time Frame
Baseline (Week -1), 6 months
Title
7-point Profile, Self-Monitored Blood Glucose (SMBG) Values
Description
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
Title
Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints
Description
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
Title
Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints
Description
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
Title
Change From Baseline in Amylase at 6-Month Endpoint
Description
Change from baseline means the absolute change from baseline (endpoint-baseline).
Time Frame
Baseline (Week -1), 6 months
Title
Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint
Description
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
Title
Percentage of Participants With Hypoglycemia
Description
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
Title
Number of Participants With Hypoglycemia
Description
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
Title
Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint
Description
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
Title
Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints
Description
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
Title
Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT -5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35242
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Artesia
State/Province
California
ZIP/Postal Code
90701
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Norwalk
State/Province
California
ZIP/Postal Code
90650
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Deland
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33316
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Plantation
State/Province
Florida
ZIP/Postal Code
33317
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67203
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Elizabeth
State/Province
New Jersey
ZIP/Postal Code
07202
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Yukon
State/Province
Oklahoma
ZIP/Postal Code
73099
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29650
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Taylors
State/Province
South Carolina
ZIP/Postal Code
29687
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Houston
State/Province
Texas
ZIP/Postal Code
77081
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Midvale
State/Province
Utah
ZIP/Postal Code
84047
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23454
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Carolina
ZIP/Postal Code
00983
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Manati
ZIP/Postal Code
00674
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
San Juan
ZIP/Postal Code
00907
Country
Puerto Rico
12. IPD Sharing Statement
Learn more about this trial
A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes
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