Clinical trial NCT00575159: A Study to Assess the Safety of Single Doses of GSK189075 in Subjects With Type 1 Diabetes Mellitus
Official title: A Double-blind, Randomized, Single Ascending Dose Escalation, Placebo-controlled, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK189075 Administered to Subjects With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: type 1 Diabetes mellitus, pharmacokinetics,
pharmacodynamics
Adult male and females,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-12-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to look at concentrations of GSK189075 in blood when single doses of the drug are taken by mouth in combination with basal insulin. The clinical effects of the drug in combination with insulin on the body will also be studied. The results will help determine doses of GSK189075 can be studied in the future in the type I diabetes mellitus population.


Eligibility criteria: Inclusion Criteria:

* Adult male/female, 18 to 55 years old
* Diagnosis of type 1 diabetes mellitus for at least 6 months; and using a continuous insulin pump
* Willing and able to follow all study-related instructions provided by the site staff.
* Willing to provide signed informed consent.

Exclusion Criteria:

* Pregnant or a nursing female.
* Have a past or current disease such as heart, liver, kidney, blood, brain, or other disease.
* Have HIV or hepatitis, or have alcohol or drugs in your system at the screening visit.
* Have a history of alcohol abuse or have an eating disorder
* Have been in another research study in the last month or have taken certain medications in the 1 week before study drug would be taken.

Primary outcomes:
measure: Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 6 months
measure: Number of Participants With Hypoglycemia Episodes/Events
timeFrame: Day 1 of each treatment period
measure: Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
timeFrame: Day 1 of each treatment period
measure: Change From Baseline Vital Signs: Heart Rate
timeFrame: Day 1 of each treatment period
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Day 1 of each treatment period
measure: Number of Participants With Abnormal Clinical Chemistry Data
timeFrame: Day 1 of each treatment period
measure: Number of Participants With Abnormal Hematology Data
timeFrame: Day 1 of each treatment period
measure: Summary of Urine Osmolality
timeFrame: Day 1 (pre dose) of each treatment period
measure: Mean Creatinine Clearance
timeFrame: Up to 24 hours post dose of each treatment period.
measure: Summary of Fluid Balance
timeFrame: Up to 24 hours post dose of each treatment period.
measure: Mean of Derived Plasma Glucose Parameters
timeFrame: Up to 24 hours post dose of each treatment period.
Secondary outcomes:
measure: Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1
timeFrame: Up to 24 hours post dose of each treatment period.
measure: Urinary Glucose Excretion (UGE) for Timed Subintervals up to 24 Hours Post Dose (0-24 H)
timeFrame: Up to 24 hours post dose of each treatment period
measure: Percent of Filtered Glucose in the Urine.
timeFrame: Up to 24 hours post dose of each treatment period.
measure: Mean Total Urine Volume 0-24 H
timeFrame: Day 1 of each treatment period
measure: Mean Creatinine Clearance 0-24 H
timeFrame: Day 1 of each treatment period
measure: Area Under the Plasma Concentration vs. Time Curve (AUC) From Time Zero (Time of Dosing) to the Last Time Point With Measurable Analyte Concentration, AUC(0-last), AUC From Time Zero to Infinite Time, AUC(0-inf) of GSK189075 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: Maximum Observed Plasma Concentration (Cmax) of GSK189075 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: AUC From Time Zero to 4 Hours Post Dose, AUC(0-4) for GSK189074 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: Oral Clearance (CL/F) Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK189074 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
measure: The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK279782 Over Period
timeFrame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Other outcomes:
Locations:
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Mudaliar S, Armstrong DA, Mavian AA, O'Connor-Semmes R, Mydlow PK, Ye J, Hussey EK, Nunez DJ, Henry RR, Dobbins RL. Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes. Diabetes Care. 2012 Nov;35(11):2198-200. doi: 10.2337/dc12-0508. Epub 2012 Sep 25.