Many patients with type 2 diabetes also have conditions that are treated with diuretics.
The patients may also be treated with GSK189075 for their diabetes. This study is planned
to assess possible effects of administering GSK189075 in combination with two frequently
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests, and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
outside the reference range for the population being studied may be included only if
the Investigator and the GSK Medical Monitor agree that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures.
- Male subjects who are between 18 and 50 years of age, inclusive.
- BMI within the range 19-30 kg/m2 (inclusive).
- Capable of providing signed and dated informed consent, which includes compliance
with the requirements and restrictions listed in the consent form and with
study-specific instructions provided by the site staff
- Significant renal disease as manifested by one or more of the following:
- Symptoms of benign prostatic hyperplasia.
- Prostate-specific antigen level of greater than 10ng/mL (or equivalent to moderately
elevated per the local lab).
- Any medical procedures requiring ingestion of radioactive agents within one week
prior to dosing with study drug.
- Cholecystectomy within 6 months before the first scheduled dose of study drug.
- Any known or suspected gastrointestinal condition (or minor gastrointestinal surgery
within 1 month prior to the first scheduled dose of study drug) that would likely
interfere with the absorption or transit of study drug.
- Any subject with either documented cirrhosis or history consistent with a diagnosis
- History of gout.
- History of sensitivity to any of the study medications, or their components, which in
the opinion of the investigator or GSK Medical Monitor, contraindicates
- History of allergy to sulfonamides, sulfonylureas, carbonic anhydrase inhibitors,
thiazides, loop diuretics (other than ethacrynic acid).
- Subjects with clinical laboratory values outside ranges specified in protocol at
screening or Day 1:
- Significant ECG abnormalities at screening according to ranges specified in the
- Systolic/Diastolic blood pressure: less than 80/60 mmHg or greater than 150/95 mmHg
- Any clinically relevant abnormality identified on the screening physical or
- Hemoglobin or hematocrit below the reference range at screening
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-
or nicotine-containing products within 6 months prior to screening.
- The subject has a positive drug/alcohol test at screening or check in into the
clinic. A minimum list of drugs that will be screened for include amphetamines,
barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines.
- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One
drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360
ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months prior to screening.
- A positive test for HIV antibody.
- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study (whichever is longer): 30 days, 5 half-lives, or twice the duration of the
biological effect of the investigational product.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
- Where participation in the study would result in donation of blood or blood products
in excess of 500mL within a 56 day period.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to latex