A Study to Assess the Safety of Single Doses of GSK189075 in Subjects With Type 1 Diabetes Mellitus

NCT00575159 | Completed Phase 2 Results

• 1 other identifier: KGI107465
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

type 1 Diabetes mellitus, pharmacokinetics,; pharmacodynamics; Adult male and females,

Outcome Measures

Primary Outcomes (11)

• Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)

  Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

  Up to 6 months

• Number of Participants With Hypoglycemia Episodes/Events

  A hypoglycemic event was defined as symptoms of hypoglycemia confirmed by a blood glucose value below normal limits \[less than 3.89 millimoles per liter (mmol/L)\] or 70 milligrams per deciliter (mg/dL). Symptoms of hypoglycemia without confirmed blood glucose values were reported as AEs instead of hypoglycemic events. Number of participants with hypoglycemic events were reported.

  Day 1 of each treatment period

• Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)

  SBP and DBP were obtained during each treatment period at the indicated time points. Measurements were made with the participant lying semi-recumbent having rested in this position for at least 10 minute before the initial reading.

  Day 1 of each treatment period

• Change From Baseline Vital Signs: Heart Rate

  Heart rate was obtained during each treatment period at indicated time points. Measurements were made with the participants lying semi-recumbent having rested in this position for at least 10 minutes before the initial reading.

  Day 1 of each treatment period

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings

  Standard semi-recumbent 12-lead ECG was obtained after the participant rested for a minimum of 10 minutes (If questionable abnormality was noted on the ECG, 2 more measurements were allowed to provide an average of 3 measurements). Number of participants with abnormal ECG were reported.

  Day 1 of each treatment period

• Number of Participants With Abnormal Clinical Chemistry Data

  Clinical Chemistry data for parameters: Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Bicarbonate, Calcium, Chloride, Creatine Kinase, Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, Lactate Dehydrogenase, Magnesium, Phosphorus, Potassium, Total Bilirubin, Sodium, Total protein, triglycerides and urea/BUN was reported. Data for number of participants with abnormal clinical Chemistry data was presented.

  Day 1 of each treatment period

• Number of Participants With Abnormal Hematology Data

  Data for abnormal Hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, Mean Corpuscle Hemoglobin (MCH), Mean Corpuscle Volume (MCV), Monocytes, Platelet count, Red Blood Cell (RBC), Reticulocytes, Total Neutrophils, White Blood Cell (WBC) were reported. Data for number of participants with abnormal Hematology were reported.

  Day 1 of each treatment period

• Summary of Urine Osmolality

  Urine sample was collected at screening, Day -2 (18:00h) and Day 1 (7:45h) for determination of urine osmolality which was measured in Millimole per kilogram (mmol/kg).

  Day 1 (pre dose) of each treatment period

• Mean Creatinine Clearance

  Creatinine clearance was calculated and reported in Milliliters per minute (mL/min) on Day 1 of each period for each collection interval 0-4, 4-8, 8-12, 12-16 and 16-24 hour, as well as the combined intervals of 0-12 and 0-24 hour. For urine measurements, participants were instructed to void within 30 minutes before administration of study medication.

  Up to 24 hours post dose of each treatment period.

• Summary of Fluid Balance

  On Day 1, fluid intake, urine volume and number of micturations were recorded over the intervals for each of the following dosing periods: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. From these measures, fluid balance was calculated over the 24-hour period. Fluid Balance=total fluid intake minus total urine volume. The 0-24h amounts of total Fluid Intake, total urine output, and fluid balance were calculated by adding the amounts collected during these time intervals.

  Up to 24 hours post dose of each treatment period.

• Mean of Derived Plasma Glucose Parameters

  The plasma measurements at specified time points on Day 1 were collected. Derived plasma glucose parameters were presented.

  Up to 24 hours post dose of each treatment period.

Secondary Outcomes (12)

• Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1

  Up to 24 hours post dose of each treatment period.

• Urinary Glucose Excretion (UGE) for Timed Subintervals up to 24 Hours Post Dose (0-24 H)

  Up to 24 hours post dose of each treatment period

• Percent of Filtered Glucose in the Urine.

  Up to 24 hours post dose of each treatment period.

• Mean Total Urine Volume 0-24 H

  Day 1 of each treatment period

• Mean Creatinine Clearance 0-24 H

  Day 1 of each treatment period

Study Arms (2)

Arm a

EXPERIMENTAL

GSK189075

Drug: GSK189075

Arm b

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

GSK189075 DRUG

investigational drug

Arm a

placebo DRUG

placebo comparator

Also known as: GSK189075

Arm b

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

San Diego, California, 92161, United States

Location

Related Publications (1)

• 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.

  PMID: 23011728 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 18, 2007
• Study Start: March 31, 2008
• Primary Completion: December 18, 2008
• Study Completion: December 18, 2008
• Last Updated: October 9, 2017
• Results First Posted: October 9, 2017

Record last verified: 2017-08

Locations

US (1)