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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Arm b
Placebo
干预措施: placebo (Drug)
Arm a
GSK189075
干预措施: GSK189075 (Drug)
结局指标
主要结局
Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: Up to 6 months
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.
Number of Participants With Hypoglycemia Episodes/Events
时间窗: Day 1 of each treatment period
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.
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
时间窗: Day 1 of each treatment period
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.
Change From Baseline Vital Signs: Heart Rate
时间窗: Day 1 of each treatment period
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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
时间窗: Day 1 of each treatment period
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.
Number of Participants With Abnormal Clinical Chemistry Data
时间窗: Day 1 of each treatment period
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.
Number of Participants With Abnormal Hematology Data
时间窗: Day 1 of each treatment period
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.
Summary of Urine Osmolality
时间窗: Day 1 (pre dose) of each treatment period
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).
Mean Creatinine Clearance
时间窗: Up to 24 hours post dose of each treatment period.
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.
Summary of Fluid Balance
时间窗: Up to 24 hours post dose of each treatment period.
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.
Mean of Derived Plasma Glucose Parameters
时间窗: Up to 24 hours post dose of each treatment period.
The plasma measurements at specified time points on Day 1 were collected. Derived plasma glucose parameters were presented.
次要结局
- 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)
- 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(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)
- Maximum Observed Plasma Concentration (Cmax) of GSK189075 Over Period(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)
- Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period(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)
- AUC From Time Zero to 4 Hours Post Dose, AUC(0-4) for GSK189074 Over Period(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)
- Oral Clearance (CL/F) Over Period(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)
- The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK189074 Over Period(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)
- The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK279782 Over Period(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)