Phase 1
Completed N=131
A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes
Source: ClinicalTrials.gov NCT00853151 ↗Enrolled (actual)
131
Serious AEs
3.8%
Results posted
Apr 2012
Primary outcomePrimary: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint — -0.08; 0.06; -0.15; 0.04 percent glycosylated hemoglobin (HbA1c) — p=0.623
Summary
Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint |
-0.08; 0.06; -0.15; 0.04 | 0.623 |
| SECONDARY Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint |
-0.81; -0.97; -0.79; -0.19 | — |
| SECONDARY Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints |
15.04; 13.14; 7.51; 28.47; -1.21; -1.05 | — |
| 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 |
44.44; -44.12; 119.23; -24.89; 221.02; -148.34 | — |
| 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 |
-0.96; -0.90; -0.16; -1.37; 0.05; -0.19 | — |
| SECONDARY Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints |
-16.76; -29.12; -47.76; -26.46; -26.48; -15.96 | — |
| 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 |
-0.90; 0.86; 1.48; -0.47; 0.41; 0.51 | — |
| SECONDARY Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints |
-1.48; -1.12; -2.90; 0.60; -0.72; -0.06 | — |
| SECONDARY Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints |
-0.7; -1.6; -1.6; 0.5; 0.1; 0.1 | — |
| 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 |
-0.36; -0.22; -0.20; -0.53; -0.17; 0.40 | — |
| 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 |
— | — |
| 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 |
— | — |
| SECONDARY Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints |
-0.198; -0.137; -0.288; 0.305; -0.561; -0.975 | — |
| SECONDARY Number of Participants With Antibodies to LY2428757 |
1; 1; 0; 0 | — |
| SECONDARY Number of Participants With Antibodies to TT223 |
0; 0; 0; 0 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax) |
0.50; 1.00 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax) |
8.52; 8.46 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis |
1.11; 1.20 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity) |
28.0; 52.2 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) |
71.4; 57.5 | — |
| 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) |
115; 99.2; 157; 136 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) |
5.61; 5.97 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax) |
0.50; 0.50 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2) |
1.08; 1.03 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity]) |
25.1; 32.6 | — |
| SECONDARY Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F) |
79.6; 92.3 | — |
| 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) |
124; 137; 163; 202 | — |
| SECONDARY Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax) |
— | — |
| SECONDARY Visual Analog Scale (VAS) for Nausea |
10.8; 5.7; 8.4; 4.7; 22.0; 27.6 | — |
| SECONDARY Change From Baseline in Waist Circumference at 6-Month Endpoint |
1.55; -0.60; -0.16; -0.33 | — |
| SECONDARY 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values |
152.75; 147.10; 142.38; 169.23; 173.18; 177.50 | — |
| SECONDARY Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints |
-29.28; -45.03; -41.18; -18.95; -24.30; -42.95 | — |
| SECONDARY Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints |
12.1; 8.1; 15.8; 2.3; 14.8; 10.1 | — |
| SECONDARY Change From Baseline in Amylase at 6-Month Endpoint |
-2.9; -4.5; 1.5; -10.3 | — |
| SECONDARY Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint |
0; 0; 2; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Hypoglycemia |
— | — |
| SECONDARY Number of Participants With Hypoglycemia |
2; 2; 3; 1 | — |
| SECONDARY Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint |
2; 0; 0; 1 | — |
| SECONDARY Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints |
6.7; -4.2; 4.7; 0.7; 2.3; -4.2 | — |
| SECONDARY Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints |
19.12; 34.73; 37.76; -14.99; -3.05; 4.41 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00853151). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.