Clinical trial NCT01029795: A Study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in Type 2 Diabetes Mellitus
Official title: A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2599506 Given as Monotherapy or in Combination With Metformin in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-12-10
Enrollment: 38
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: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change From Baseline in the QT Interval in Electrocardiogram (ECG) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Homeostasis Model Assessment (HOMA2) Pancreatic Beta Cell Function (%B) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Homeostasis Model Assessment (HOMA2) of Insulin Sensitivity (%S) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: 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
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the European Quality of Life -5 Dimension (EQ-5D) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Adult Low Blood Sugar Survey (LBSS-33 Item Scale) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Changes From Baseline in the Diabetes Symptoms Checklist-Revised (DSC-R) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Perceptions About Medications - Diabetes (PAM-D) Questionnaire at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Number of Hypoglycemic Episodes During 12-week Treatment Period and 4-week Follow-up Period
timeFrame: Baseline through 16 weeks
measure: Change From Baseline in Body Weight at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Change From Baseline in the Seven-Point Self-Monitored Blood Glucose (7-point SMBG) at 4 Weeks, 12 Weeks, and 16 Weeks
timeFrame: Baseline, 4 weeks, 12 weeks, 16 weeks
measure: Percentage of Participants With Lipase and Amylase Measurements Above 2-fold Upper Limits of Normal (ULN) During the 12-week Treatment Period
timeFrame: Baseline through 12 weeks
measure: Percentage of Participants With Clinically-Significant Elevations of Alanine Aminotransferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT) During the 12-week Treatment Period
timeFrame: Baseline through 12 weeks
measure: Maximum Plasma Concentration (Cmax) at the Steady State for LY2599506
timeFrame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12
measure: Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506
timeFrame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12
measure: 30-day Adjusted Rates of Self-reported Hypoglycemic Episodes Overall
timeFrame: Baseline through 16 weeks
measure: Change From Baseline in Heart Rate at 12 Weeks and 16 Weeks
timeFrame: Baseline, 12 weeks, 16 weeks
measure: Mean Morning Dose of LY2599506 During the 12-week Treatment Period
timeFrame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.
measure: Mean Afternoon Dose of LY2599506 During the 12-week Treatment Period
timeFrame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.
measure: Percentage of Participants Requiring Dose Adjustments During the 12-week Treatment Period
timeFrame: Baseline through 12 weeks
measure: Mean Total Daily Dose of LY2599506 During the 12-week Treatment Period
timeFrame: Baseline through 12 weeks.
Other outcomes:
Locations:
city: Elizabeth Vale
country: Australia
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 Australia
city: East Ringwood
country: Australia
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: Victoria
city: Heidelberg
country: Australia
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: Victoria
city: Vienna
country: Austria
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: Holesov
country: Czech Republic
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: Prague
country: Czech Republic
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: Mainz
country: Germany
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: Neuss
country: Germany
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: Jerusalem
country: Israel
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: Nahariya
country: Israel
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: Rostov-On-Don
country: Russian Federation
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: Saint Petersburg
country: Russian Federation
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: Barcelona
country: Spain
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: Cordoba
country: Spain
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: Dos Hermanas
country: Spain
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: Teruel
country: Spain
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 9AM - 5PM Eastern Time (UTC/GMT - 5hours, EST)
role: STUDY_DIRECTOR
References: