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

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

Measures the QT interval in the ECG. 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 was not analyzed.

Time frame: 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

HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. 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 was not calculated or analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

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

HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population was set at 100%. 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 was not calculated or analyzed.

Time frame: 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

Fasting lipids were measured after an overnight fast. Lipids measured included triglycerides, HDL-C, LDL-C, non-HDL-C, total cholesterol, and free fatty acids. 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.

Time frame: Baseline, 12 weeks, 16 weeks

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

Assesses 5 health domains: mobility, self-care, usual activity, pain, and anxiety/depression with 3 options each. Total scores range from 5 (no problem) to 15 (more severe or frequent problems). An algorithm maps the 5 domain outcomes to a single index (0-1). A higher score indicates better perceived health state. 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 was not analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

Change From Baseline in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 Weeks and 16 Weeks

DTSQ, an 8-item questionnaire, measures satisfaction with treatment, perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. 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 was not analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

Change From Baseline in the Adult Low Blood Sugar Survey (LBSS-33 Item Scale) at 12 Weeks and 16 Weeks

Assesses 2 hypoglycemia domains, with each item score from 0 (never engages in behavior) to 4 (always engages in behavior): Behavioral (15 items; range 0-60) and Worry about hypoglycemia (18 items; range 0-72). Total score is the sum of both domains (range 0-132). Higher scores indicate greater negative impact. 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. As a result, this outcome measure was not analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

Changes From Baseline in the Diabetes Symptoms Checklist-Revised (DSC-R) at 12 Weeks and 16 Weeks

Comprise 6 subscales (34 items). Each item score: 1 (not troublesome) to 5 (extremely troublesome) and transformed to 0-4 scale. Subscale score=sum of item scale in each subscale/total number of items. Global score=sum of scores by dimension. All scores standardized (0-100). Higher scores=greater symptom burden. 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 was not analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

Change From Baseline in the Perceptions About Medications - Diabetes (PAM-D) Questionnaire at 12 Weeks and 16 Weeks

PAM-D assesses participants' perceptions about their diabetes medications during the past month. Responses ranged from "None of the time," to "All of the time." The sum of all items in the scale equals the scale score, which was linearly transformed to a 0 (least favorable state) to 100 (most favorable state). 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 was not analyzed.

Time frame: Baseline, 12 weeks, 16 weeks

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 12 Weeks and 16 Weeks

Change in SBP and DBP following 12 weeks of therapy (Week 12 SBP minus SBP at baseline; Week 12 DBP minus DBP at baseline) and 16 weeks of therapy (Week 16 SBP minus SBP at baseline; Week 16 DBP minus DBP 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.

Time frame: Baseline, 12 weeks, 16 weeks

Number of Hypoglycemic Episodes During 12-week Treatment Period and 4-week Follow-up Period

Hypoglycemia was defined as any time a participant felt s/he was experiencing a sign or symptom associated with hypoglycemia or had a blood glucose \<70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]) even if it was not associated with signs or symptoms of hypoglycemia. Study GMAJ was terminated after enrolling only 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.

Time frame: Baseline through 16 weeks

Change From Baseline in Body Weight at 12 Weeks and 16 Weeks

Weight was measured in the fasting state (with the exception of Visit 1) and after emptying the bladder. Participants were instructed to be lightly clothed and without shoes. 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.

Time frame: Baseline, 12 weeks, 16 weeks

Change From Baseline in the Seven-Point Self-Monitored Blood Glucose (7-point SMBG) at 4 Weeks, 12 Weeks, and 16 Weeks

SMBG levels were measured at the following 7 timepoints during the day: fasting prebreakfast, 2 hours post-breakfast, prior to lunch, 2 hours post-lunch, prior to dinner, 2 hours postdinner, and prior to bed. Study GMAJ was terminated after enrolling only 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.

Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks

Percentage of Participants With Lipase and Amylase Measurements Above 2-fold Upper Limits of Normal (ULN) During the 12-week Treatment Period

Lipase and amylase concentrations were assessed. Amylase normal limits for males and females are 28-100 units per liter (U/L) (18-50 years), 28-120 U/L (50-60 years), and 28-150 U/L (60-70 years). Normal lipase limits for males and females are 0-100 U/L (18-50 years; 50-60 years) and 0-120 U/L (60-70 years). Study GMAJ was terminated after enrolling only 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.

Time frame: Baseline through 12 weeks

Percentage of Participants With Clinically-Significant Elevations of Alanine Aminotransferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT) During the 12-week Treatment Period

Clinically significant elevations of ALT/SGPT were considered ≥3 times the upper limit of normal (ULN). The percentage of participants above 2- and 5-fold ULN was not analyzed due to the early termination of the trial. The percentage of participants with ALT 3-fold ULN or higher is presented.

Time frame: Baseline through 12 weeks

Maximum Plasma Concentration (Cmax) at the Steady State for LY2599506

The Cmax value measures the maximum plasma concentration at steady state following administration of doses of LY2599506. Due to the nature of the sparse sampling approach, Cmax was estimated using the posthoc pharmacokinetic (PK) parameters obtained from Population PK (PopPK) modeling. 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.

Time frame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12

Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506

The AUCtau values measure the area under the plasma concentration time curve at a dosing interval at steady state for LY2599506. Due to the nature of sparse sampling approach taken for the study AUC tau was estimated using the posthoc pharmacokinetic (PK) parameters obtained from Population PK (Pop PK) modeling. 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 was not analyzed.

Time frame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12

30-day Adjusted Rates of Self-reported Hypoglycemic Episodes Overall

Hypoglycemia: any time a participant experienced a sign/symptom associated with hypoglycemia or had blood glucose \<70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter \[mmol/L\]). The 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days. Study GMAJ was terminated after enrolling 38 participants. Given 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.

Time frame: Baseline through 16 weeks

Change From Baseline in Heart Rate at 12 Weeks and 16 Weeks

Heart rate was measured in heartbeats per minute. 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.

Time frame: Baseline, 12 weeks, 16 weeks

Mean Morning Dose of LY2599506 During the 12-week Treatment Period

Assigned morning dose, in milligrams (mg), for each participant at each visit. 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.

Time frame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.

Mean Afternoon Dose of LY2599506 During the 12-week Treatment Period

Assigned afternoon dose, in milligrams (mg), for each participant at each visit. 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.

Time frame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.

Percentage of Participants Requiring Dose Adjustments During the 12-week Treatment Period

Percentage of participants who required dose adjustments at the discretion of the investigator for participants with persistent blood glucose\<70 milligrams per deciliter (mg/dL). 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.

Time frame: Baseline through 12 weeks

Mean Total Daily Dose of LY2599506 During the 12-week Treatment Period

The average total daily dose (sum of assigned morning and afternoon doses), in milligrams (mg), at each visit. 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.

Time frame: Baseline through 12 weeks.