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

This study has been terminated.
(Terminated due to nonclinical safety findings)
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01029795
First received: December 9, 2009
Last updated: November 29, 2011
Last verified: November 2011
Results First Received: September 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: LY2599506
Drug: Glyburide
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
LY2599506 Participants received up to 4 capsules by mouth (po), twice daily (BID), in combinations of 50 milligram (mg) or 100 mg capsules of LY2599506 or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) LY2599506 was administered, based on predefined glycemic targets, in escalating doses from 100 mg/day up to 800 mg/day.
Glyburide Participants received up to 4 capsules po BID in combinations of 2.5-mg capsules of Glyburide or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) Glyburide was administered, based on predefined glycemic targets, in escalating doses from 5 mg/day up to 20 mg/day.

Participant Flow:   Overall Study
    LY2599506     Glyburide  
STARTED     16     22  
COMPLETED     0     0  
NOT COMPLETED     16     22  
Entry Criteria Not Met                 2                 1  
Physician Decision                 2                 1  
Sponsor Decision                 11                 17  
Withdrawal by Subject                 1                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
LY2599506 Participants received up to 4 capsules by mouth (po), twice daily (BID), in combinations of 50 milligram (mg) or 100 mg capsules of LY2599506 or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) LY2599506 was administered, based on predefined glycemic targets, in escalating doses from 100 mg/day up to 800 mg/day.
Glyburide Participants received up to 4 capsules po BID in combinations of 2.5-mg capsules of Glyburide or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) Glyburide was administered, based on predefined glycemic targets, in escalating doses from 5 mg/day up to 20 mg/day.
Total Total of all reporting groups

Baseline Measures
    LY2599506     Glyburide     Total  
Number of Participants  
[units: participants]
  16     22     38  
Age  
[units: years]
Mean ± Standard Deviation
  59.76  ± 6.74     59.38  ± 5.86     59.54  ± 6.16  
Gender  
[units: participants]
     
Female     6     7     13  
Male     10     15     25  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     0     1     1  
Not Hispanic or Latino     16     21     37  
Unknown or Not Reported     0     0     0  
Region of Enrollment [1]
[units: participants]
     
Australia     5     9     14  
Austria     2     3     5  
Czech Republic     1     2     3  
Israel     2     1     3  
Russian Federation     2     2     4  
Spain     4     5     9  
Duration of Diabetes in Years  
[units: year]
Mean ± Standard Deviation
  6.08  ± 5.03     7.73  ± 5.64     7.03  ± 5.38  
Percentage of Glycosylated Fraction of Hemoglobin A1c [2]
[units: percentage of glycosylated hemoglobin]
Mean ± Standard Deviation
  7.90  ± 0.75     7.78  ± 1.02     7.83  ± 0.91  
[1] There were no participants from Germany.
[2] HbA1c: hemoglobin A1c, glycosylated fraction of hemoglobin A (%)



  Outcome Measures
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1.  Primary:   Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks   [ Time Frame: Baseline, 12 weeks ]

2.  Secondary:   Change From Baseline in the QT Interval in Electrocardiogram (ECG) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

3.  Secondary:   Change From Baseline in the Homeostasis Model Assessment (HOMA2) Pancreatic Beta Cell Function (%B) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

4.  Secondary:   Change From Baseline in the Homeostasis Model Assessment (HOMA2) of Insulin Sensitivity (%S) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

5.  Secondary:   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   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

6.  Secondary:   Change From Baseline in the European Quality of Life -5 Dimension (EQ-5D) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

7.  Secondary:   Change From Baseline in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

8.  Secondary:   Change From Baseline in the Adult Low Blood Sugar Survey (LBSS-33 Item Scale) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

9.  Secondary:   Changes From Baseline in the Diabetes Symptoms Checklist-Revised (DSC-R) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

10.  Secondary:   Change From Baseline in the Perceptions About Medications – Diabetes (PAM-D) Questionnaire at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

11.  Secondary:   Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

12.  Secondary:   Number of Hypoglycemic Episodes During 12-week Treatment Period and 4-week Follow-up Period   [ Time Frame: Baseline through 16 weeks ]

13.  Secondary:   Change From Baseline in Body Weight at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

14.  Secondary:   Change From Baseline in the Seven-Point Self-Monitored Blood Glucose (7-point SMBG) at 4 Weeks, 12 Weeks, and 16 Weeks   [ Time Frame: Baseline, 4 weeks, 12 weeks, 16 weeks ]

15.  Secondary:   Percentage of Participants With Lipase and Amylase Measurements Above 2-fold Upper Limits of Normal (ULN) During the 12-week Treatment Period   [ Time Frame: Baseline through 12 weeks ]

16.  Secondary:   Percentage of Participants With Clinically-Significant Elevations of Alanine Aminotransferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT) During the 12-week Treatment Period   [ Time Frame: Baseline through 12 weeks ]

17.  Secondary:   Maximum Plasma Concentration (Cmax) at the Steady State for LY2599506   [ Time Frame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12 ]

18.  Secondary:   Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506   [ Time Frame: Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12 ]
  Hide Outcome Measure 18

Measure Type Secondary
Measure Title Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data were reviewed but are not presented due to the insufficient sample size and sparse sampling approach.

Reporting Groups
  Description
LY2599506 Participants received up to 4 capsules by mouth (po), twice daily (BID), in combinations of 50 milligram (mg) or 100 mg capsules of LY2599506 or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) LY2599506 was administered, based on predefined glycemic targets, in escalating doses from 100 mg/day up to 800 mg/day.
Glyburide Participants received up to 4 capsules po BID in combinations of 2.5-mg capsules of Glyburide or matching placebo capsules. (Each dose contained at least 1 capsule of active drug.) Glyburide was administered, based on predefined glycemic targets, in escalating doses from 5 mg/day up to 20 mg/day.

Measured Values
    LY2599506     Glyburide  
Number of Participants Analyzed  
[units: participants]
  0     0  
Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506  
[units: nanograms per milliliter times hour]
Mean ± Standard Deviation
       

No statistical analysis provided for Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506



19.  Secondary:   30-day Adjusted Rates of Self-reported Hypoglycemic Episodes Overall   [ Time Frame: Baseline through 16 weeks ]

20.  Secondary:   Change From Baseline in Heart Rate at 12 Weeks and 16 Weeks   [ Time Frame: Baseline, 12 weeks, 16 weeks ]

21.  Secondary:   Mean Morning Dose of LY2599506 During the 12-week Treatment Period   [ Time Frame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks. ]

22.  Secondary:   Mean Afternoon Dose of LY2599506 During the 12-week Treatment Period   [ Time Frame: Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks. ]

23.  Secondary:   Percentage of Participants Requiring Dose Adjustments During the 12-week Treatment Period   [ Time Frame: Baseline through 12 weeks ]

24.  Secondary:   Mean Total Daily Dose of LY2599506 During the 12-week Treatment Period   [ Time Frame: Baseline through 12 weeks. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


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