Clinical trial NCT00853151: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: OPKO Health, Inc.
First posted: 2009-03-02
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.


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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint
timeFrame: Baseline (Week -1), 6 months
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint
timeFrame: Baseline (Week -1), 4 weeks
measure: Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: 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
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: 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
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 3 weeks, 6 months
measure: Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 4 weeks, 6 months
measure: 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
timeFrame: Baseline (Week -1), 6 months
measure: 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
timeFrame: Baseline (Week -1), Week 0, 3 weeks, 3.5 months, 6 months
measure: 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
timeFrame: Baseline (Week -1), 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months
measure: Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints
timeFrame: Baseline (Week -1), Week 0, 4 weeks, 6 months
measure: Number of Participants With Antibodies to LY2428757
timeFrame: Baseline (Week -1) through 6 months
measure: Number of Participants With Antibodies to TT223
timeFrame: Baseline (Week -1) through 6 months
measure: Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: 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)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity])
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: 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)
timeFrame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours
measure: Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)
timeFrame: 0 (pre-dose)
measure: Visual Analog Scale (VAS) for Nausea
timeFrame: 4 weeks, 6 months
measure: Change From Baseline in Waist Circumference at 6-Month Endpoint
timeFrame: Baseline (Week -1), 6 months
measure: 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values
timeFrame: Baseline (Week -1), 4 weeks, 6 months
measure: Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 4 weeks, 6 months
measure: Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints
timeFrame: Baseline (Week -1), Week 0, 4 weeks, 6 months
measure: Change From Baseline in Amylase at 6-Month Endpoint
timeFrame: Baseline (Week -1), 6 months
measure: Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint
timeFrame: Baseline (Week -1) through 6 months
measure: Percentage of Participants With Hypoglycemia
timeFrame: Baseline (Week -1) through 6 months
measure: Number of Participants With Hypoglycemia
timeFrame: Baseline (Week -1) through 6 months
measure: Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint
timeFrame: Baseline (Week -1) through 6 months
measure: Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 4 weeks, 6 months
measure: Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints
timeFrame: Baseline (Week -1), 3 weeks, 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 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.
state: Alabama
city: Anaheim
country: United States
facility: 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.
state: California
city: Artesia
country: United States
facility: 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.
state: California
city: Fresno
country: United States
facility: 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.
state: California
city: Greenbrae
country: United States
facility: 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.
state: California
city: Norwalk
country: United States
facility: 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.
state: California
city: Deland
country: United States
facility: 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.
state: Florida
city: Fort Lauderdale
country: United States
facility: 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.
state: Florida
city: Miami
country: United States
facility: 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.
state: Florida
city: Plantation
country: United States
facility: 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.
state: Florida
city: West Palm Beach
country: United States
facility: 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.
state: Florida
city: Idaho Falls
country: United States
facility: 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.
state: Idaho
city: Topeka
country: United States
facility: 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.
state: Kansas
city: Wichita
country: United States
facility: 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.
state: Kansas
city: Metairie
country: United States
facility: 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.
state: Louisiana
city: Elizabeth
country: United States
facility: 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.
state: New Jersey
city: Yukon
country: United States
facility: 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.
state: Oklahoma
city: Eugene
country: United States
facility: 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.
state: Oregon
city: Greer
country: United States
facility: 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.
state: South Carolina
city: Taylors
country: United States
facility: 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.
state: South Carolina
city: Kingsport
country: United States
facility: 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.
state: Tennessee
city: Dallas
country: United States
facility: 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.
state: Texas
city: Houston
country: United States
facility: 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.
state: Texas
city: San Antonio
country: United States
facility: 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.
state: Texas
city: Midvale
country: United States
facility: 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.
state: Utah
city: Virginia Beach
country: United States
facility: 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.
state: Virginia
city: Carolina
country: Puerto Rico
facility: 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
country: Puerto Rico
facility: 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
country: Puerto Rico
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: