A Study To Assess The Safety And Tolerability Of GSK189075 When Given With A Total Daily Dose Of >/ 2000mg of Metformin

Study Overview
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Brief Summary
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This study will assess safety and tolerability of metformin plus GSK189075 in people with Type 2 Diabetes. About 48 people will participate in this study. Volunteers will not know if they are receiving GSK189075 or a placebo. Participation will last about 5 weeks including a run-in period of up to 2 weeks if necessary to increase metformin up to 2000mg daily, a 13-day treatment period, and a follow-up visit about 1 week after the treatment period. Volunteers will remain in the research clinic beginning 2 days before they receive the first dose of GSK189075 until after the morning dose on the fourth day and from the afternoon of the 12th day of dosing until the morning after the last dose. They will have clinic visits on dosing Days 6, 8, and 10. Volunteers will be given equipment and instructions for measuring their blood sugar at home and will be asked to keep a study diary. Blood pressure, heart rate, laboratory tests on blood and urine, physical examinations, reports of drug side effects and ECGs will be obtained during the clinic visits to assess safety.

Official Title
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A Two-Week, Randomized, Double-Blind, Repeat-Dose, Parallel-Group Study to Evaluate the Safety and Tolerability of Metformin > 2000mg Co-Administered With Either GSK189075 500mg BID or GSK 189075 750mg BID to Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: GSK189075
* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Type 2 Diabetes for at least three months prior to study Diabetes treated with metformin only Give consent and sign an informed consent form. Agree to follow specific requirements of birth control during participation. Exclusion Criteria: Type I Diabetes. Treatment with insulin within 3 months prior to screening History of diabetic ketoacidosis or lactic acidosis Allergy or sensitivity to metformin or similar drugs or any medical conditions which prohibit metformin use Excessive blood donation 56 days before the start of the study Urinary tract or bladder infections within four weeks of study start Alcohol abuse or illicit drug use within 12 months of study start Receiving other investigational drugs or participating in other research trials within 30 of the study start Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements with 7-14 days of study start Live alone without regular, daily interactions with someone who can be an emergency contact

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Subjects receiving treatment P<br>Eligible subjects will receive placebo twice daily along with metformin twice daily for 13 days. | Drug: Metformin<br>* Metformin will be available as an immediate release oral tablet with dosing strengths of 500 milligrams and 850 milligrams.<br>Drug: Placebo<br>* Placebo will be available as an oral tablets.<br>|
| Experimental: Subjects receiving treatment A<br>Eligible subjects will receive GSK189075 500 milligrams twice daily along with metformin twice daily for 13 days. | Drug: GSK189075<br>* GSK189075 will be available as an oral tablet with dosing strengths of 500 milligrams and 250 milligrams.<br>Drug: Metformin<br>* Metformin will be available as an immediate release oral tablet with dosing strengths of 500 milligrams and 850 milligrams.<br>|
| Experimental: Subjects receiving treatment B<br>Eligible subjects will receive GSK189075 750 milligrams twice daily along with metformin twice daily for 13 days. | Drug: GSK189075<br>* GSK189075 will be available as an oral tablet with dosing strengths of 500 milligrams and 250 milligrams.<br>Drug: Metformin<br>* Metformin will be available as an immediate release oral tablet with dosing strengths of 500 milligrams and 850 milligrams.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical laboratory tests, ECGs, physical exam & adverse events: |  | screening, in-clinic stays, outpatient clinic visits &amp; follow up visit (approximately 50 days) | 
| Home diary of blood sugar results, adverse events and drug dosing. |  | throughout the study (approximately 50 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| study drug blood levels: |  | Dosing Days 1 & 13 metformin blood levels: Days -1 & 13 | 
| Blood glucose & insulin levels following oral glucose challenge: |  | Dosing Days -1 & 13 | 
| fluid intake & output |  | dosing Days -1 - 3, 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, GSK189075,, Metformin,, Safety,, Diabetes,