A Comparison Of Study Drug Blood Levels After One Dose Of GSK189075 In Subjects With Normal And Reduced Kidney Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00501462
First received: July 13, 2007
Last updated: March 15, 2012
Last verified: June 2011
  Purpose

This is an open-label study that will measure blood levels of different parts of a drug called GKS189075. People participating in this study will receive a single dose of 250mg GSK189075 by mouth. About 20 people with mild to moderate decrease in renal (kidney) function will be asked to participate in this study. They will be compared to about 20 healthy participants who are close to the same age and body size. People participating in this study will stay at a clinical research unit beginning 2 days before they receive their single dose of GSK189075 and will remain there until approximately one day after receiving the study drug. During this study urine will be collected beginning the day before receiving study drug until the day after, just prior to leaving the clinical research unit. Blood samples will also be collected at various times beginning immediately before until 24 hours after receiving the study drug.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Diabetes Mellitus, Type 2
Renal Insufficiency
Drug: GSK189075
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Evaluation of the Pharmacokinetics of a Single Oral Dose of GSK189075 in Patients With Varying Degrees of Renal Insufficiency Compared to Volunteers With Normal Renal Function

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • drug & metabolite plasma levels [ Time Frame: at 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, & 24 hours after dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • urine levels of Glucose & electrolytes, Drug & metabolites [ Time Frame: at 0-6, 6-12 & 12-24 hours after dosing ] [ Designated as safety issue: Yes ]
  • ECG, labs, vital signs, adverse events [ Time Frame: each visit ] [ Designated as safety issue: Yes ]
  • Plasma protein binding of GSK189074 and GSK279782 [ Time Frame: 2 hr ] [ Designated as safety issue: No ]
  • GSK189074 and GSK279782 in 24 hour urine collection and corresponding renal clearance CLr. [ Time Frame: 24 hr ] [ Designated as safety issue: No ]
  • urine glucose excreted. [ Time Frame: 6, 12, 24 hours ] [ Designated as safety issue: No ]
  • Urinary creatinine clearance (CLcr). [ Time Frame: 6, 12, 24 hours ] [ Designated as safety issue: No ]
  • Safety and tolerability parameters, including AEs and clinically relevant changes in vital signs (heart rate and blood pressure), ECGs, urine electrolytes, and clinical laboratory assessments (clinical chemistry, hematology, and urinalysis). [ Time Frame: 1, 2, 4, 12, 24 hours ] [ Designated as safety issue: Yes ]

Enrollment: 29
Study Start Date: July 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Mild renal impairmnent Drug: GSK189075
single 250 mg dose of drug
Other Name: GSK189075
moderate renal impairment Drug: GSK189075
single 250 mg dose of drug
Other Name: GSK189075
Normal renal function Drug: GSK189075
single 250 mg dose of drug
Other Name: GSK189075

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A female is eligible to enter and participate in this study if she is of Non-child-bearing potential with a negative pregnancy test at screening or of Childbearing potential, has a negative serum pregnancy test at screening, is not lactating, and agrees to adequate contraception.
  • Satisfactory medical evaluation based upon medical history, medication history, physical examination, and clinical laboratory data obtained at the Screening visit.
  • Body weight > 50 kg. BMI within the range of 19 to 40 kg/m2.
  • Signed and dated written informed consent prior to participation in any protocol-specific procedures, including screening procedures.
  • The subject is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions.
  • Additional Inclusion Criteria for Subjects with Renal Insufficiency: Subjects with renal insufficiency must be considered by the investigator to be clinically stable. Subjects must continue to meet this criterion of stable renal function upon check-in into the clinic

Exclusion Criteria:

  • History of regular alcohol consumption averaging >7 drinks per week for women or >14 drinks per week for men within 6 months of Screening. One drink is equivalent to 12 g alcohol = 5 ounces (oz; 150 ml) of wine or 12 oz (360 ml) of beer or 1.5 oz (45 ml) of 80 proof distilled spirits.
  • A positive drug or alcohol test at Screening or Check-in.
  • Smokers will be allowed to enrol in the study; however, smoking that interferes with the collection/recording of ongoing study procedures will not be allowed. Smoking status will be recorded in the CRF.
  • The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication for the current study.
  • The subject has donated more than 450mL blood within the 56 day period prior to the first scheduled administration of GSK189075.
  • Known or suspected gastroparesis, gastric surgery within the 6 months prior to screening, or any other gastrointestinal condition that would likely interfere with absorption of GSK189075.
  • Subjects with clinical laboratory values outside rages as specified in the protocols
  • Any subject with either documented cirrhosis or a history consistent with a diagnosis of cirrhosis.
  • Urinary tract or bladder infection within 4 weeks of the first scheduled administration of study drug.
  • Positive hepatitis B surface antigen, or HIV at Screening. If negative test results have been documented within the last 2 months, it will not be necessary to repeat these tests. Subjects with positive results for hepatitis C antibodies may be eligible if they have normal liver enzymes and no history of hepatitis and are approved by the GSK medical monitor.
  • Any history of myocardial infarction, cardiac syncope.
  • A history of clinically significant cardiac arrhythmias (individual cases to be discussed with the GSK Medical Monitor).
  • A history of unstable angina in the past 6 months.
  • Cardiac conduction abnormalities denoted by ranges specified in the protocol
  • Systolic blood pressure < 80 mmHg or > 180 mmHg
  • Diastolic blood pressure < 60 mmHg or > 100 mmHg
  • Use of prescription or non-prescription drugs (including high dose vitamins, herbal and dietary supplements [including St. John's Wort]) within 7 days prior to administration of the first dose of study medication, unless in the opinion of the investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety. Some allowable exceptions are found in the Permitted Medications section (Section 9.1).

Additional Exclusion Criteria for Subjects with Renal Insufficiency

  • Patients on a new drug regimen (defined as starting a new drug or changing dosage regimen of a current drug within 7 days prior to administration of GSK189075). No restrictions will be placed on the use of insulin, 1,25 dihydroxyvitamin D3 (Rocaltrol), erythropoietin, and calcium- or aluminum-containing phosphate binders.
  • Subjects whose current medication therapy is not in agreement with the information provided in Sections 9.1, 9.2, or 9.3 of this protocol.
  • Serum albumin less than 2.5 g/dL.
  • Hemoglobin less than 8.5 g/dL. Additional Exclusion Criteria for Subjects with Normal Renal Function
  • Any clinically relevant abnormality identified on the screening physical or laboratory examination. Any abnormalities of outside the normal reference range at Screening may be repeated once and must be reviewed with the GSK Medical Monitor prior to enrollment of a subject into the study.
  • Hemoglobin or hematocrit below the reference range at Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501462

Locations
United States, Florida
GSK Investigational Site
Orlando, Florida, United States, 32809
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
United States, Tennessee
GSK Investigational Site
Knoxville, Tennessee, United States, 37920
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78752
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00501462     History of Changes
Other Study ID Numbers: KG2105253
Study First Received: July 13, 2007
Last Updated: March 15, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Type 2 Diabetes Mellitus
renal insufficiency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Renal Insufficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014