A Study To Compare Effects Of GSK189075 In Combination With Either Furosemide Or Hydrochlorothiazide

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

An Evaluation of the Safety, Tolerability, and Pharmacodynamic Effects of GSK189075 When Administered With Furosemide or Hydrochlorothiazide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671424
• Other study ID #: KG2105251
• Status: Completed
• Phase: Phase 1
• First received: April 30, 2008
• Last updated: March 15, 2012
• Start date: March 2008
• Est. completion date: May 2008

Study information

• Verified date: February 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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 used diuretics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 of cirrhosis.

• 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 participation.

• 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 protocol:

• Systolic/Diastolic blood pressure: less than 80/60 mmHg or greater than 150/95 mmHg at screening.

• Any clinically relevant abnormality identified on the screening physical or laboratory examination.

• 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 subject safety.

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Hydrochlorothiazide (HCTZ)

• Remogliflozin etabonate (GSK189075)

• Furosemide

Locations

Country	Name	City	State
United States	GSK Investigational Site	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum sodium and potassium concentrations:		baseline, Day 3, and Days 9-15
Secondary	adverse events:		each visit
Secondary	Physical Exam:		screening,Days -1,15,follow-up
Secondary	ECG & vital signs:		Days -1,3,8,9,14,15,follow-up
Secondary	Clinical labs:screening:		Days -1,3,8-15,follow-up
Secondary	blood pressure:		days 7,13
Secondary	urine labs:		Days 7,8,9,13,14
Secondary	weight:		Days -1,3,4,9,10,15