A Study to Test the Combination of Two Different Kinds of Medications for the Treatment of Diabetes - Full Text View

Sponsor:	Eli Lilly and Company
Collaborator:	Transition Therapeutics
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00853151

Purpose

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

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: LY2428757 Drug: TT223 Drug: Placebo for LY2428757 Drug: Placebo for TT223	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Change in A1C [ Time Frame: baseline (-1 week), 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in A1C [ Time Frame: baseline, 0, 4 weeks, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: No ]
Change in MMTT response (including postprandial glucose, glucose AUC, insulin/c-peptide secretory response, HOMA, GLP-1, glucagon) [ Time Frame: baseline, 0, 3 weeks, 3.5 months, 6 months ] [ Designated as safety issue: No ]
Change in fasting blood glucose [ Time Frame: baseline, 0, 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: No ]
Change in A1C adjusted for baseline A1c, c-peptide level, homeostasis model assessment of insulin resistance, duration of diabetes and weight [ Time Frame: baseline, 0, 4 weeks, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: No ]
Change in MMTT response (includes postprandial glucose,glucose AUC,insulin/c-peptide secretory response,HOMA,GLP-1,glucagon) adjusted for baseline A1c, c-peptide level, homeostasis model assessment of insulin resistance, duration of diabetes and weight [ Time Frame: baseline, 0, 3 weeks, 3.5 months, 6 months ] [ Designated as safety issue: No ]
Change in fasting blood glucose adjusted for baseline A1c, c-peptide level, homeostasis model assessment of insulin resistance, duration of diabetes and weight [ Time Frame: baseline, 0, 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: No ]
Mean changes in weight [ Time Frame: baseline, 6 months ] [ Designated as safety issue: Yes ]
Antibodies to LY2428757 [ Time Frame: Baseline, 4 weeks, 2 months, 6 months ] [ Designated as safety issue: Yes ]
Antibodies to TT223 [ Time Frame: Baseline, 4 weeks, 2 months, 6 months ] [ Designated as safety issue: Yes ]
Pharmacokinetics (PKs) of TT223, first dose [ Time Frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours ] [ Designated as safety issue: No ]
Pharmacokinetics (PKs) of TT223, 3-week timepoint [ Time Frame: 0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours ] [ Designated as safety issue: No ]
Pharmacokinetics (PKs) of LY2428757, 3 week timepoint [ Time Frame: 0 (pre-dose) ] [ Designated as safety issue: No ]
Visual Analog Scale (VAS) for nausea [ Time Frame: baseline, 0, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 months ] [ Designated as safety issue: No ]
Change in waist circumference [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
7 point profile, self-monitored blood glucose values [ Time Frame: baseline, 4 weeks, 6 months ] [ Designated as safety issue: No ]
Change in 7 point profile, self-monitored blood glucose [ Time Frame: baseline, 4 weeks, 6 months ] [ Designated as safety issue: No ]
Change in Lipase [ Time Frame: baseline, after run-in treatment, 3 weeks, 4 weeks, 3.5 months, 6 months ] [ Designated as safety issue: Yes ]
Change in Amylase [ Time Frame: baseline, after run-in treatment, 3 weeks, 4 weeks, 3.5 months, 6 months ] [ Designated as safety issue: Yes ]
Percent with 2-fold elevation of lipase and/or amylase at any timepoint [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Rate of hypoglycemia [ Time Frame: -3 weeks, baseline, 0, 1 week, 2 week, 3 week, 4 week, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: Yes ]
Incidence of hypoglycemia [ Time Frame: -3 weeks, baseline, 0, 1 week, 2 week, 3 week, 4 week, 2 months, 3.5 months, 5 months, 6 months ] [ Designated as safety issue: Yes ]
Number of adjudicated and confirmed deaths and non-fatal CV events at any timepoint [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Change in fasting insulin and HOMA [ Time Frame: baseline, 0, 3 weeks, 4 weeks, 2 months, 3.5 months, 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	February 2009
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
LY2428757 plus TT223 3mg: Experimental Weekly LY2428757 plus 3 mg daily TT223	Drug: LY2428757 14 mg subcutaneous injection one time a week for 5 weeks Drug: TT223 subcutaneous injection once a day for 4 weeks
LY2428757 plus TT223 2mg: Experimental Weekly LY2428757 plus 2 mg daily TT223	Drug: LY2428757 14 mg subcutaneous injection one time a week for 5 weeks Drug: TT223 subcutaneous injection once a day for 4 weeks
LY2428757 plus placebo: Experimental Weekly LY2428757 plus daily TT223 placebo	Drug: LY2428757 14 mg subcutaneous injection one time a week for 5 weeks Drug: Placebo for TT223 subcutaneous injection once a day for 4 weeks
Placebo plus Placebo: Placebo Comparator Weekly LY2428757 placebo plus daily TT223 placebo	Drug: Placebo for LY2428757 subcutaneous injection one time a week for 5 weeks Drug: Placebo for TT223 subcutaneous injection once a day for 4 weeks

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Written informed consent
Have T2DM for at least 6 months
Currently diet and exercise alone or in combination with stable metformin
A1c 7.0% to 10.0%
Ages 18 to 70 years
Women not of childbearing potential
BMI between 25 and 40 kg/m2, 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 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, 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.
ECG abnormality or medication that impairs the ability to measure the QT, or correct the QT for rate.
QTcBazett (QTcB) interval >450 msec or PR interval >220 msec
Personal or family history of long 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/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 81-325mg
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 patient 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853151

Show 29 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Transition Therapeutics

Investigators

Study Director:

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)

Eli Lilly and Company

More Information

No publications provided

Responsible Party:	Eli Lilly ( Chief Medical Officer )
ClinicalTrials.gov Identifier:	NCT00853151 History of Changes
Other Study ID Numbers:	12758, I3H-MC-GAFA(b)
Study First Received:	February 26, 2009
Last Updated:	December 14, 2009
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 02, 2010