A Study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in Type 2 Diabetes Mellitus

NCT01029795 | Terminated Phase 2 Results

• 2 other identifiers: 13272I2Q-MC-GMAJ
• Study Type: interventional
• Target: 38
• Locations: 6 countries
• Sites: 13

Brief Summary

The purpose of this study is to help answer the following research question(s):

• To test if taking LY2599506 for 12 weeks controls blood sugar better than taking glyburide for 12 weeks.
• To evaluate the safety of LY2599506 in participants with diabetes.
• To determine if LY2599506 has the ability to control blood sugar in participants with diabetes.
• To determine how much LY2599506 should be given to participants.
• To determine if LY2599506 has an effect on a participant's weight. The study design consists of 4 study periods: a screening period, a 4-week dose adjustment period, an 8-week treatment period, and a 4-week follow up period.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks

  Change in HbA1c from baseline following 12 weeks of therapy (HbA1c at week 12 minus HbA1c at baseline). Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.

  Baseline, 12 weeks

Secondary Outcomes (23)

• Change From Baseline in the QT Interval in Electrocardiogram (ECG) at 12 Weeks and 16 Weeks

  Baseline, 12 weeks, 16 weeks

• Change From Baseline in the Homeostasis Model Assessment (HOMA2) Pancreatic Beta Cell Function (%B) at 12 Weeks and 16 Weeks

  Baseline, 12 weeks, 16 weeks

• Change From Baseline in the Homeostasis Model Assessment (HOMA2) of Insulin Sensitivity (%S) at 12 Weeks and 16 Weeks

  Baseline, 12 weeks, 16 weeks

• Change From Baseline in Triglycerides, Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, Total Cholesterol, and Free Fatty Acids at 12 Weeks and 16 Weeks

  Baseline, 12 weeks, 16 weeks

• Change From Baseline in the European Quality of Life -5 Dimension (EQ-5D) at 12 Weeks and 16 Weeks

  Baseline, 12 weeks, 16 weeks

Study Arms (2)

LY2599506

EXPERIMENTAL

Combinations of 50-milligram (mg) or 100-mg capsules of LY2599506 or matching placebo capsules (each dose contains at least 1 capsule of active drug). LY2599506 will be administered, based on predefined glycemic targets, in escalating doses from 100 mg/day up to 800 mg/day.

Drug: LY2599506; Drug: Placebo

Glyburide

ACTIVE COMPARATOR

Combinations of 2.5-mg capsules of Glyburide or matching placebo capsules (each dose contains at least 1 capsule of active drug). Glyburide will be administered, based on predefined glycemic targets, in escalating doses from 5 mg/day up to 20 mg/day.

Drug: Glyburide; Drug: Placebo

Interventions

LY2599506 DRUG

Administered orally (po), twice daily (BID) prior to morning and evening meals for 12 weeks

Also known as: Glucokinase Activator 1

LY2599506

Glyburide DRUG

Administered po, BID daily prior to morning and evening meals for 12 weeks

Glyburide

Placebo DRUG

Matching placebo capsules administered po, BID prior to morning and evening meals for 12 weeks

Glyburide; LY2599506

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have type 2 diabetes mellitus prior to entering the trial
• Are currently being treated with diet and exercise therapy consistent with the local standards of medical care
• Treated with: Diet and exercise alone; or Diet and exercise in combination with a stable dose of metformin for at least 3 months prior to entering the trial; or Diet and exercise in combination with a stable dose of sulfonylurea for at least 3 months prior to entering the trial; or Diet and exercise in combination with stable doses of metformin and sulfonylurea for at least 3 months prior to entering the trial and have had diabetes for at least 6 years.
• Have an HbA1c value between 7% and 10%
• Are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Male patients will be advised to use a reliable method of birth control during the study and until 3 months after the last dose of study medication if their partner is of child-bearing potential.

You may not qualify if:

• Use of insulin or any antidiabetic agent other than metformin or sulfonylurea during the 3 months prior to entering the trial.
• Have a gastrointestinal disease that significantly impacts gastric emptying or motility (for example, severe gastroparesis or pyloric stenosis), in the opinion of the Investigator, or have undergone gastric bypass or gastric banding surgery.
• Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness
• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
• Have cardiac autonomic neuropathy (for example, resting tachycardia or orthostatic hypotension), based on clinical signs, symptoms, or appropriate diagnostic testing.
• Have cardiac disease with functional status that is New York Heart Association 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 (that is, mean systolic blood pressure \>160 mm Hg or mean diastolic blood pressure \>100 mm Hg) 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 fed or fasting state hypertriglyceridemia (defined as \>6.8 millimoles per liter \[mmol/L\], 600 milligrams per deciliter \[mg/dL\]) at screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or repeated alanine transaminase (ALT) levels \>2.5 times the upper limit of the reference range at screening.
• Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as judged by the Investigator at screening.
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (16)

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.

Elizabeth Vale, South Australia, 5112, Australia

Location

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.

East Ringwood, Victoria, 3135, Australia

Location

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.

Heidelberg, Victoria, 3081, Australia

Location

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.

Vienna, 1090, Austria

Location

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.

Holešov, 769 01, Czechia

Location

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.

Prague, 140 59, Czechia

Location

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.

Mainz, 55116, Germany

Location

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.

Neuss, D-41460, Germany

Location

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.

Jerusalem, 91120, Israel

Location

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.

Nahariya, 22100, Israel

Location

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.

Rostov-on-Don, 344022, Russia

Location

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.

Saint Petersburg, 191126, Russia

Location

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.

Barcelona, 08022, Spain

Location

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.

Córdoba, 14004, Spain

Location

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.

Dos Hermanas, 41014, Spain

Location

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.

Teruel, 44002, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Limitations and Caveats

Since Study GMAJ was terminated after enrolling only 38 participants with just 1 participant completing 12 weeks of treatment, only disposition, demographics, and safety data are reported.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern Time (UTC/GMT - 5hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2009
• First Posted: December 10, 2009
• Study Start: February 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 2, 2011
• Results First Posted: October 26, 2011

Record last verified: 2011-11

Locations

RU (2); CZ (2); AU (1); DE (2); IL (2); ES (4)