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

History of Changes

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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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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 ]

Show Outcome Measure 1

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 ]

Show Outcome Measure 2

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 ]

Show Outcome Measure 3

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 ]

Show Outcome Measure 4

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 ]

Show Outcome Measure 5

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 ]

Show Outcome Measure 6

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 ]

Show Outcome Measure 7

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 ]

Show Outcome Measure 8

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 ]

Show Outcome Measure 9

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 ]

Show Outcome Measure 10

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 ]

Show Outcome Measure 11

12. Secondary:

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

Show Outcome Measure 12

13. Secondary:

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

Show Outcome Measure 13

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 ]

Show Outcome Measure 14

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 ]

Show Outcome Measure 15

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 ]

Show Outcome Measure 16

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 ]

Show Outcome Measure 17

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 ]

Show Outcome Measure 18

19. Secondary:

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

Show Outcome Measure 19

20. Secondary:

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

Show Outcome Measure 20

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. ]

Show Outcome Measure 21

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. ]

Show Outcome Measure 22

23. Secondary:

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

Show Outcome Measure 23

24. Secondary:

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

Show Outcome Measure 24

Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	4%

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.

Other Adverse Events

	LY2599506	Glyburide
Total, other (not including serious) adverse events
# participants affected / at risk	5/16	5/22
Eye disorders
Vision blurred ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Gastrointestinal disorders
Abdominal discomfort ^{† 1}
# participants affected / at risk	1/16 (6.25%)	0/22 (0.00%)
# events	1	0
Constipation ^{† 1}
# participants affected / at risk	1/16 (6.25%)	0/22 (0.00%)
# events	1	0
Nausea ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
General disorders
Asthenia ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Fatigue ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Infections and infestations
Infectious mononucleosis ^{† 1}
# participants affected / at risk	1/16 (6.25%)	0/22 (0.00%)
# events	1	0
Influenza ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Lower respiratory tract infection ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Nasopharyngitis ^{† 1}
# participants affected / at risk	0/16 (0.00%)	1/22 (4.55%)
# events	0	1
Nervous system disorders
Headache ^{† 1}
# participants affected / at risk	2/16 (12.50%)	0/22 (0.00%)
# events	2	0

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0

More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

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.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

No publications provided

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01029795 History of Changes
Other Study ID Numbers:	13272, I2Q-MC-GMAJ
Study First Received:	December 9, 2009
Results First Received:	September 15, 2011
Last Updated:	November 29, 2011
Health Authority:	United States: Food and Drug Administration Spain: Comité Ético de Investigación Clínica Spain: Spanish Agency of Medicines Russia: Ethics Committee Russia: FSI Scientific Center of Expertise of Medical Application Russia: Ministry of Health of the Russian Federation Germany: Federal Institute for Drugs and Medical Devices Germany: Ethics Commission Czech Republic: Ethics Committee Czech Republic: State Institute for Drug Control Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: Human Research Ethics Committee Australia: National Health and Medical Research Council Austria: Agency for Health and Food Safety Hungary: Institutional Ethics Committee Hungary: National Institute of Pharmacy Israel: Ministry of Health

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