A Study in Patients With Type 2 Diabetes

Phase 2

Withdrawn

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Glimepiride; Drug: LY2608204

• Registration Number: NCT01408095
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The study is designed to see if once daily oral dosing of LY2608204 will help control diabetes as measured by the glycosylated fraction of hemoglobin A (HbA1c) level. It will also help to determine the safety of the medication and the most useful doses of the medication.

Detailed Description

Not available

Study Timeline

• Status Verified: 2011-08
• Study First Submitted: 2011-08-01
• Study First Submitted QC: 2011-08-01
• Study First Posted: 2011-08-03
• Last Update Submitted: 2011-08-23
• Last Update Posted: 2011-08-25
• Study Start: 2011-09
• Primary Completion: 2012-09
• Study Completion: 2012-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Clinical diagnosis of type 2 diabetes mellitus prior to entering the trial

• May be treated with:

  1. Diet and exercise alone or
  2. Diet and exercise in combination with a stable dose of metformin for at least 3 months before Screening or
  3. Diet and exercise in combination with a stable dose of sulfonylurea or meglitinide (repaglinide, nateglinide) for at least 3 months before Screening or
  4. Diet and exercise in combination with stable doses of metformin and sulfonylurea or metformin and meglitinides for at least 3 months before Screening and have had diabetes for at least 6 years

• Must have an Hemoglobin A1c value between 7% and 10%

• Must have a body mass index (BMI) between 20 and 40 kg/m2

• Must have stable weight during the 3 months prior to Screening (weight change not to exceed 5 kg (11 lb))

• If female, you must not be able to get pregnant

• Must be well motivated, capable, and willing to complete study required glucose monitoring and instruction

Exclusion Criteria

• Use of insulin or any antidiabetic agent other than metformin or sulfonylurea or meglitinide during the 3 months prior to Screening
• Have a gastrointestinal disease that significantly impacts gastric emptying or motility or have undergone gastric bypass or gastric banding surgery
• Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness or have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months
• Are currently taking or have taken within the last 2 months, prescription or over-the counter medications which affect body weight
• Have cardiac disease with functional status that is New York Heart Association [NYHA] Class II, III, or IV or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure in the past 6 months.
• Have poorly controlled hypertension, history of malignant hypertension, evidence of renal artery stenosis and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization
• Have a QTcB (Bazett's-corrected QT interval) interval greater than 450 msec for men or greater than 470 for women at Screening or any personal history of ventricular tachycardia or unexplained syncope
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or significantly elevated liver blood tests
• Are currently receiving renal dialysis, have a serum creatinine greater than 2.0 mg/dL (177 μmol/L) or a calculated creatinine clearance of less than 60 ml/min or in patients being treated with metformin, have other known contradictions to metformin use including, but not limited to, a serum creatinine above (or creatinine clearance below) what is approved in the metformin product label
• Have fasting state hypertriglyceridemia (defined as greater than 5.65 mmol/L, 500 mg/dl) at Screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.
• Are receiving chronic (for more than 2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to Randomization
• Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
• Have a history of seizure disorder
• Are currently using or intend to use inhibitors of Cytochrome P450 family 3A (CYP3A4)
• Currently taking a medication that is a sensitive substrate of the CYP3A4 pathway with a narrow therapeutic index

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glimepiride	Glimepiride	1 to 6 mg, Doses will be titrated to reach glycemic targets during the first 4 weeks. Administered orally, daily for 12 weeks
LY2608204	LY2608204	80 to 400 mg, Doses will be titrated to reach glycemic targets during the first 4 weeks. The starting dose level depends on the participant's HbA1c level measured at Screening. Administered orally, daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change from baseline to 12 week endpoint in glycosylated fraction of hemoglobin A (HbA1c)	Baseline, 12 Weeks

Secondary Outcome Measures

Name	Time	Method
Change from baseline to 12 week endpoint in fasting blood glucose	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in average Seven Point Self Monitored Blood Glucose	Baseline, 12 Weeks
Change from baseline to 12 week endpoint for Oral Glucose Tolerance Test (OGTT)	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in Homa-B: Insulin	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in Homa-IR: Insulin	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in Homa-S: Insulin	Baseline, 12 weeks
Change from baseline to 12 week endpoint in fasting lipids	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in free fatty acids	Baseline, 12 Weeks
Change from baseline to 12 week endpoint in body weight	Baseline, 12 Weeks
Incidence of Hypoglycemic Episodes	Baseline through 12 weeks
Percentage of participants at each dose level up to 12 weeks	Baseline up to 12 weeks
Pharmacokinetics: Maximum plasma concentration (Cmax) of LY2608204	pre-dose, up to 12 hours post-dose
Number of participants with severe hypoglycemic episodes	Baseline through 12 weeks
Rate of hypoglycemic episodes	Baseline through 12 weeks
Pharmacokinetics: Area under the curve of concentration-time curve for one dosing interval at steady state (AUC0-tau, ss) of LY2608204	pre-dose, up to 12 hours post-dose

Trial Locations

Locations (1)

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.; 🇪🇸 Sevilla, Spain