Trial Outcomes & Findings for A Study to Assess the Safety of Single Doses of GSK189075 in Subjects With Type 1 Diabetes Mellitus (NCT NCT00575159)
NCT ID: NCT00575159
Last Updated: 2017-10-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Up to 6 months
Results posted on
2017-10-09
Participant Flow
A total of 10 participants with type 1 diabetes mellitus (T1DM) were randomized in this study. Study was conducted between 31 Mach 2008 to 19 January 2009 at a single center in the United States (US).
Participants were screened within 28 days of the first dose and a total of 10 participants were randomized to receive the study drug. The participants were admitted on Day -2 and were analyzed of all Baseline safety and glucose control on Day -1.
Participant milestones
| Measure |
Overall Study Arm
Participants received 5 treatments P0, P1, A, B, C in each of the treatment period in a randomized manner separated by a 5 to 35-day washout period between treatments, where Treatment P0 consisted of Basal insulin \[continuous subcutaneous insulin injection (CSII)\], mealtime placebo injection, and placebo tablet. Treatment P1 consisted of CSII, mealtime bolus insulin injection, and Placebo tablet. Treatment A consisted of CSII, mealtime placebo injection, GSK189075 50 milligram (mg) tablet. Treatment B consisted of CSII, mealtime placebo injection, GSK189075 150 mg tablet. Treatment C consisted of CSII, mealtime placebo injection, GSK189075 500 mg tablet. The two placebo sessions (P0 and P1) were designed to provide information about the relative efficacy of GSK189075 versus each individual participant's usual mealtime insulin bolus. The number of tablets administered will be same for each treatment arm.
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|---|---|
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Overall Study
STARTED
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10
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Overall Study
COMPLETED
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10
|
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Safety of Single Doses of GSK189075 in Subjects With Type 1 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Overall Study Arm
n=10 Participants
Participants received 5 treatments P0, P1, A, B, C in each of the treatment period in a randomized manner separated by a 5 to 35-day washout period between treatments, where Treatment P0 consisted of Basal insulin \[continuous subcutaneous insulin injection (CSII)\], mealtime placebo injection, and placebo tablet. Treatment P1 consisted of CSII, mealtime bolus insulin injection, and Placebo tablet. Treatment A consisted of CSII, mealtime placebo injection, GSK189075 50 mg tablet. Treatment B consisted of CSII, mealtime placebo injection, GSK189075 150 mg tablet. Treatment C consisted of CSII, mealtime placebo injection, GSK189075 500 mg tablet. The two placebo sessions (P0 and P1) were designed to provide information about the relative efficacy of GSK189075 versus each individual participant's usual mealtime insulin bolus. The number of tablets administered will be same for each treatment arm.
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|---|---|
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Age, Continuous
|
42.9 Years
STANDARD_DEVIATION 8.08 • n=5 Participants
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Sex: Female, Male
Female
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3 Participants
n=5 Participants
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Sex: Female, Male
Male
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7 Participants
n=5 Participants
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|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
White
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10 Participants
n=5 Participants
|
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: Safety Population comprised of all enrolled participants who have received at least one dose of study drug were included in the safety population.
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
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Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
Any AE
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3 Participants
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4 Participants
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5 Participants
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6 Participants
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4 Participants
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Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
Any SAE
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0 Participants
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0 Participants
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0 Participants
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0 Participants
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0 Participants
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PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
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Number of Participants With Hypoglycemia Episodes/Events
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5 Participants
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5 Participants
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3 Participants
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5 Participants
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6 Participants
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PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,0.5 H
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1.6 Millimeters of mercury (mmHg)
Standard Deviation 10.63
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-5.1 Millimeters of mercury (mmHg)
Standard Deviation 5.32
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-0.7 Millimeters of mercury (mmHg)
Standard Deviation 18.03
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-3.4 Millimeters of mercury (mmHg)
Standard Deviation 12.97
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-1.9 Millimeters of mercury (mmHg)
Standard Deviation 8.82
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,1 H
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1.8 Millimeters of mercury (mmHg)
Standard Deviation 14.70
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-1.7 Millimeters of mercury (mmHg)
Standard Deviation 9.17
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-4.7 Millimeters of mercury (mmHg)
Standard Deviation 12.78
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-7.8 Millimeters of mercury (mmHg)
Standard Deviation 8.77
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5.6 Millimeters of mercury (mmHg)
Standard Deviation 14.75
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,2 H
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-1.8 Millimeters of mercury (mmHg)
Standard Deviation 14.01
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-6.5 Millimeters of mercury (mmHg)
Standard Deviation 6.29
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-5.1 Millimeters of mercury (mmHg)
Standard Deviation 14.30
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-3.5 Millimeters of mercury (mmHg)
Standard Deviation 13.19
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-2.2 Millimeters of mercury (mmHg)
Standard Deviation 9.38
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,4 H
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-2.9 Millimeters of mercury (mmHg)
Standard Deviation 11.86
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-0.9 Millimeters of mercury (mmHg)
Standard Deviation 7.56
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-8.4 Millimeters of mercury (mmHg)
Standard Deviation 8.37
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-2.5 Millimeters of mercury (mmHg)
Standard Deviation 18.52
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-4.3 Millimeters of mercury (mmHg)
Standard Deviation 7.49
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,6 H
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-2.1 Millimeters of mercury (mmHg)
Standard Deviation 9.88
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-5.5 Millimeters of mercury (mmHg)
Standard Deviation 13.10
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-8.2 Millimeters of mercury (mmHg)
Standard Deviation 7.18
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-8.4 Millimeters of mercury (mmHg)
Standard Deviation 15.43
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-6.9 Millimeters of mercury (mmHg)
Standard Deviation 13.58
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,8 H
|
-1.4 Millimeters of mercury (mmHg)
Standard Deviation 13.12
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-2.1 Millimeters of mercury (mmHg)
Standard Deviation 10.80
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-3.2 Millimeters of mercury (mmHg)
Standard Deviation 10.21
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-7.3 Millimeters of mercury (mmHg)
Standard Deviation 18.50
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-2.4 Millimeters of mercury (mmHg)
Standard Deviation 12.56
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Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
SBP,Day1,24 H
|
2.6 Millimeters of mercury (mmHg)
Standard Deviation 7.27
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-1.4 Millimeters of mercury (mmHg)
Standard Deviation 11.77
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-0.4 Millimeters of mercury (mmHg)
Standard Deviation 9.54
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-0.2 Millimeters of mercury (mmHg)
Standard Deviation 12.20
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-4.6 Millimeters of mercury (mmHg)
Standard Deviation 12.85
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,0.5 H
|
-1.1 Millimeters of mercury (mmHg)
Standard Deviation 10.36
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-5.3 Millimeters of mercury (mmHg)
Standard Deviation 9.38
|
-9.8 Millimeters of mercury (mmHg)
Standard Deviation 11.73
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-7.4 Millimeters of mercury (mmHg)
Standard Deviation 13.13
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-5.2 Millimeters of mercury (mmHg)
Standard Deviation 13.36
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,1 H
|
-5.4 Millimeters of mercury (mmHg)
Standard Deviation 11.61
|
-7.7 Millimeters of mercury (mmHg)
Standard Deviation 12.31
|
-11.5 Millimeters of mercury (mmHg)
Standard Deviation 8.32
|
-15.1 Millimeters of mercury (mmHg)
Standard Deviation 11.06
|
-5.7 Millimeters of mercury (mmHg)
Standard Deviation 9.59
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,2 H
|
-8.8 Millimeters of mercury (mmHg)
Standard Deviation 7.50
|
-8.7 Millimeters of mercury (mmHg)
Standard Deviation 11.29
|
-11.7 Millimeters of mercury (mmHg)
Standard Deviation 10.04
|
-11.0 Millimeters of mercury (mmHg)
Standard Deviation 12.72
|
-7.2 Millimeters of mercury (mmHg)
Standard Deviation 10.55
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,4 H
|
-6.4 Millimeters of mercury (mmHg)
Standard Deviation 7.52
|
-6.4 Millimeters of mercury (mmHg)
Standard Deviation 13.08
|
-11.7 Millimeters of mercury (mmHg)
Standard Deviation 7.45
|
-8.5 Millimeters of mercury (mmHg)
Standard Deviation 13.04
|
-7.7 Millimeters of mercury (mmHg)
Standard Deviation 9.84
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,6 H
|
-8.4 Millimeters of mercury (mmHg)
Standard Deviation 8.88
|
-7.0 Millimeters of mercury (mmHg)
Standard Deviation 10.70
|
-13.2 Millimeters of mercury (mmHg)
Standard Deviation 8.31
|
-12.3 Millimeters of mercury (mmHg)
Standard Deviation 15.36
|
-8.0 Millimeters of mercury (mmHg)
Standard Deviation 12.91
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,8 H
|
-2.2 Millimeters of mercury (mmHg)
Standard Deviation 7.79
|
-5.8 Millimeters of mercury (mmHg)
Standard Deviation 9.24
|
-10.1 Millimeters of mercury (mmHg)
Standard Deviation 5.76
|
-10.7 Millimeters of mercury (mmHg)
Standard Deviation 15.40
|
-4.7 Millimeters of mercury (mmHg)
Standard Deviation 15.05
|
|
Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
DBP,Day1,24 H
|
0.5 Millimeters of mercury (mmHg)
Standard Deviation 9.97
|
1.6 Millimeters of mercury (mmHg)
Standard Deviation 11.55
|
-4.2 Millimeters of mercury (mmHg)
Standard Deviation 6.71
|
-3.6 Millimeters of mercury (mmHg)
Standard Deviation 11.51
|
-2.0 Millimeters of mercury (mmHg)
Standard Deviation 9.51
|
PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
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Change From Baseline Vital Signs: Heart Rate
Day 1,0.5 H
|
-1.4 beats/minute
Standard Deviation 9.69
|
-5.4 beats/minute
Standard Deviation 8.57
|
-4.5 beats/minute
Standard Deviation 7.21
|
-4.7 beats/minute
Standard Deviation 7.58
|
-5.2 beats/minute
Standard Deviation 12.67
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,1 H
|
1.7 beats/minute
Standard Deviation 11.46
|
-2.8 beats/minute
Standard Deviation 8.65
|
-1.4 beats/minute
Standard Deviation 8.23
|
-4.3 beats/minute
Standard Deviation 11.20
|
-5.1 beats/minute
Standard Deviation 12.96
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,2 H
|
1.0 beats/minute
Standard Deviation 13.79
|
-4.0 beats/minute
Standard Deviation 7.90
|
-4.4 beats/minute
Standard Deviation 8.22
|
-3.3 beats/minute
Standard Deviation 7.42
|
-5.1 beats/minute
Standard Deviation 14.05
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,4 H
|
-1.4 beats/minute
Standard Deviation 11.37
|
-4.6 beats/minute
Standard Deviation 10.46
|
-6.5 beats/minute
Standard Deviation 7.94
|
-2.6 beats/minute
Standard Deviation 9.79
|
-6.8 beats/minute
Standard Deviation 10.90
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,6 H
|
2.5 beats/minute
Standard Deviation 11.20
|
-2.0 beats/minute
Standard Deviation 8.46
|
-1.3 beats/minute
Standard Deviation 10.36
|
3.5 beats/minute
Standard Deviation 11.54
|
-1.4 beats/minute
Standard Deviation 12.17
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,8 H
|
0.7 beats/minute
Standard Deviation 12.48
|
-6.6 beats/minute
Standard Deviation 10.60
|
-4.6 beats/minute
Standard Deviation 6.95
|
1.6 beats/minute
Standard Deviation 10.16
|
-3.4 beats/minute
Standard Deviation 12.04
|
|
Change From Baseline Vital Signs: Heart Rate
Day 1,24 H
|
5.4 beats/minute
Standard Deviation 13.92
|
6.6 beats/minute
Standard Deviation 11.67
|
4.2 beats/minute
Standard Deviation 10.99
|
10.0 beats/minute
Standard Deviation 11.50
|
0.4 beats/minute
Standard Deviation 12.39
|
PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY 1 PRE-DOSE (2)
|
1 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -2
|
0 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -2 (2)
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -2 (3)
|
0 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -1
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -1 (2)
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY -1 (3)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY 1 PRE-DOSE
|
1 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY 1 PRE-DOSE (3)
|
1 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY 1 4 H
|
2 Participants
|
1 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
DAY 1 24 H
|
2 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population. Only those participants available at the specific time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1 ,PRE-DOSE,Low
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1, 24 H,High
|
7 Participants
|
8 Participants
|
6 Participants
|
7 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1, 24 H,Normal
|
3 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1, 24 H,Low
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Lactate Dehydrogenase,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
5 Participants
|
6 Participants
|
4 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Magnesium,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Phosphorus, inorganic,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Potassium,DAY 1, PRE-DOSE,High
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Potassium,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Potassium,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
8 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Sodium,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Sodium,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Bilirubin,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
6 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Bilirubin,DAY 1, PRE-DOSE,Low
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Bilirubin,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Protein,DAY 1, PRE-DOSE,Normal
|
4 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Protein,DAY 1 ,PRE-DOSE,Low
|
2 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALT,DAY 1, PRE-DOSE,Normal
|
4 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALT,DAY 1 ,PRE-DOSE,Low
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALT,DAY 1, 24 H,Normal
|
8 Participants
|
8 Participants
|
7 Participants
|
6 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALT,DAY 1, 24 H,Low
|
2 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALT,DAY 1, 24 H,Missing
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Albumin,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Albumin,DAY 1, 24 H,High
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Albumin,DAY 1, 24 H,Normal
|
9 Participants
|
10 Participants
|
9 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALP,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
ALP,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
AST,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
6 Participants
|
6 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
AST,DAY 1 ,PRE-DOSE,Low
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
AST,DAY 1, 24 H,Normal
|
9 Participants
|
9 Participants
|
6 Participants
|
6 Participants
|
8 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
AST,DAY 1, 24 H,Low
|
1 Participants
|
1 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
AST,DAY 1, 24 H,Missing
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Bicarbonate,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Bicarbonate,DAY 1 ,PRE-DOSE,Low
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Calcium,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Chloride,DAY 1, PRE-DOSE,High
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Chloride,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Chloride,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Creatine Kinase,DAY 1, PRE-DOSE,High
|
2 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Creatine Kinase,DAY 1, PRE-DOSE,Normal
|
4 Participants
|
4 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Creatinine,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Creatinine,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
GGT,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
5 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
GGT,DAY 1, PRE-DOSE,Missing
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
GGT,DAY 1, 24 H,Normal
|
10 Participants
|
10 Participants
|
9 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1, PRE-DOSE,High
|
3 Participants
|
5 Participants
|
4 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Glucose,DAY 1, PRE-DOSE,Normal
|
2 Participants
|
1 Participants
|
3 Participants
|
3 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Protein,DAY 1, 24 H,Normal
|
9 Participants
|
9 Participants
|
10 Participants
|
9 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Total Protein,DAY 1, 24 H,Low
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Triglycerides,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Urea/BUN,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Urea/BUN,DAY 1, 24 H,Normal
|
10 Participants
|
8 Participants
|
10 Participants
|
10 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Clinical Chemistry Data
Urea/BUN,DAY 1, 24 H,Low
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population. Only those participants available at the specific time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Hematology Data
Platelet count,DAY 1, 24 H,Low
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
RBC,DAY 1 ,PRE-DOSE,Low
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Reticulocytes,DAY 1, PRE-DOSE,High
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Reticulocytes,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
RBC,DAY 1, 24 H,Normal
|
2 Participants
|
2 Participants
|
3 Participants
|
4 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology Data
RBC,DAY 1, 24 H,Low
|
7 Participants
|
8 Participants
|
6 Participants
|
5 Participants
|
9 Participants
|
|
Number of Participants With Abnormal Hematology Data
Basophils,DAY 1, PRE-DOSE,High
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Basophils,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Basophils,DAY 1, 24 H,High
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Data
Basophils,DAY 1, 24 H,Normal
|
7 Participants
|
8 Participants
|
9 Participants
|
9 Participants
|
8 Participants
|
|
Number of Participants With Abnormal Hematology Data
Eosinophils,DAY 1, PRE-DOSE,High
|
5 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Eosinophils,DAY 1, PRE-DOSE,Normal
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Eosinophils,DAY 1, 24 H,High
|
5 Participants
|
4 Participants
|
4 Participants
|
4 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Hematology Data
Eosinophils,DAY 1, 24 H,Normal
|
4 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hematocrit,DAY 1, PRE-DOSE,Normal
|
2 Participants
|
1 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hematocrit,DAY 1 ,PRE-DOSE,Low
|
4 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hematocrit,DAY 1, 24 H,Normal
|
4 Participants
|
6 Participants
|
7 Participants
|
8 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hematocrit,DAY 1, 24 H,Low
|
5 Participants
|
4 Participants
|
2 Participants
|
1 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hemoglobin,DAY 1, PRE-DOSE,Normal
|
4 Participants
|
4 Participants
|
6 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hemoglobin,DAY 1 ,PRE-DOSE,Low
|
2 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hemoglobin,DAY 1, 24 H,Normal
|
7 Participants
|
8 Participants
|
7 Participants
|
8 Participants
|
8 Participants
|
|
Number of Participants With Abnormal Hematology Data
Hemoglobin,DAY 1, 24 H,Low
|
2 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Data
Lymphocytes,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Lymphocytes,DAY 1 ,PRE-DOSE,Low
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Lymphocytes,DAY 1, 24 H,High
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Lymphocytes,DAY 1, 24 H,Normal
|
9 Participants
|
8 Participants
|
8 Participants
|
7 Participants
|
9 Participants
|
|
Number of Participants With Abnormal Hematology Data
Lymphocytes,DAY 1, 24 H,Low
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCH,DAY 1, PRE-DOSE,High
|
4 Participants
|
3 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCH,DAY 1, PRE-DOSE,Normal
|
2 Participants
|
3 Participants
|
3 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCHC,DAY 1, PRE-DOSE,High
|
4 Participants
|
4 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCHC,DAY 1, PRE-DOSE,Normal
|
2 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCV,DAY 1, PRE-DOSE,High
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology Data
MCV,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Hematology Data
Monocytes,DAY 1, PRE-DOSE,High
|
2 Participants
|
2 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology Data
Monocytes,DAY 1, PRE-DOSE,Normal
|
4 Participants
|
4 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Hematology Data
Monocytes,DAY 1, 24 H,High
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology Data
Monocytes,DAY 1, 24 H,Normal
|
9 Participants
|
8 Participants
|
8 Participants
|
8 Participants
|
9 Participants
|
|
Number of Participants With Abnormal Hematology Data
Platelet count,DAY 1, PRE-DOSE,Normal
|
6 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Platelet count,DAY 1, 24 H,Normal
|
9 Participants
|
10 Participants
|
9 Participants
|
8 Participants
|
10 Participants
|
|
Number of Participants With Abnormal Hematology Data
Reticulocytes,DAY 1, PRE-DOSE,Missing
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Total Neutrophils,DAY 1, PRE-DOSE,High
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Total Neutrophils,DAY 1, PRE-DOSE,Normal
|
5 Participants
|
5 Participants
|
6 Participants
|
4 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology Data
Total Neutrophils,DAY 1 ,PRE-DOSE,Low
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology Data
Total Neutrophils,DAY 1, 24 H,High
|
2 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
Total Neutrophils,DAY 1, 24 H,Normal
|
7 Participants
|
7 Participants
|
8 Participants
|
8 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Hematology Data
WBC,DAY 1, PRE-DOSE,Normal
|
3 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
WBC,DAY 1 ,PRE-DOSE,Low
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology Data
WBC,DAY 1, 24 H,Normal
|
8 Participants
|
7 Participants
|
8 Participants
|
9 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Hematology Data
WBC,DAY 1, 24 H,Low
|
1 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Day 1 (pre dose) of each treatment periodPopulation: Safety Population. Only those participants available at the specified time points were analyzed.
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).
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Summary of Urine Osmolality
DAY 1,PRE-DOSE
|
330.5 mmol/kg
Standard Deviation 88.89
|
364.4 mmol/kg
Standard Deviation 100.89
|
425.0 mmol/kg
Standard Deviation 257.05
|
304.3 mmol/kg
Standard Deviation 73.13
|
441.8 mmol/kg
Standard Deviation 87.61
|
|
Summary of Urine Osmolality
DAY -2
|
631.8 mmol/kg
Standard Deviation 226.85
|
651.6 mmol/kg
Standard Deviation 229.44
|
647.1 mmol/kg
Standard Deviation 314.81
|
618.3 mmol/kg
Standard Deviation 314.15
|
702.2 mmol/kg
Standard Deviation 167.39
|
PRIMARY outcome
Timeframe: Up to 24 hours post dose of each treatment period.Population: Safety Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Mean Creatinine Clearance
0-4 H
|
116.9 mL/min
Standard Deviation 43.28
|
134.5 mL/min
Standard Deviation 38.76
|
130.2 mL/min
Standard Deviation 44.13
|
142.2 mL/min
Standard Deviation 66.83
|
134.3 mL/min
Standard Deviation 61.43
|
|
Mean Creatinine Clearance
4-8 H
|
111.5 mL/min
Standard Deviation 42.94
|
129.6 mL/min
Standard Deviation 54.27
|
122.7 mL/min
Standard Deviation 52.45
|
102.3 mL/min
Standard Deviation 31.01
|
134.0 mL/min
Standard Deviation 34.48
|
|
Mean Creatinine Clearance
8-12 H
|
131.3 mL/min
Standard Deviation 63.82
|
123.3 mL/min
Standard Deviation 52.40
|
105.6 mL/min
Standard Deviation 37.92
|
140.6 mL/min
Standard Deviation 54.35
|
120.4 mL/min
Standard Deviation 43.29
|
|
Mean Creatinine Clearance
12-16 H
|
120.8 mL/min
Standard Deviation 49.47
|
117.9 mL/min
Standard Deviation 66.22
|
125.3 mL/min
Standard Deviation 78.45
|
89.5 mL/min
Standard Deviation 50.43
|
117.8 mL/min
Standard Deviation 61.66
|
|
Mean Creatinine Clearance
16-24 H
|
100.5 mL/min
Standard Deviation 40.47
|
119.5 mL/min
Standard Deviation 62.30
|
120.8 mL/min
Standard Deviation 33.73
|
126.4 mL/min
Standard Deviation 64.91
|
120.0 mL/min
Standard Deviation 33.91
|
|
Mean Creatinine Clearance
0-12 H
|
119.9 mL/min
Standard Deviation 34.08
|
129.1 mL/min
Standard Deviation 28.34
|
119.5 mL/min
Standard Deviation 28.74
|
128.4 mL/min
Standard Deviation 37.85
|
132.7 mL/min
Standard Deviation 24.28
|
|
Mean Creatinine Clearance
0-24 H
|
113.6 mL/min
Standard Deviation 30.30
|
124.0 mL/min
Standard Deviation 35.48
|
120.9 mL/min
Standard Deviation 30.05
|
121.3 mL/min
Standard Deviation 38.01
|
128.2 mL/min
Standard Deviation 26.45
|
PRIMARY outcome
Timeframe: Up to 24 hours post dose of each treatment period.Population: Safety Population.
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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Summary of Fluid Balance
Total Fluid Intake,0-4h
|
1240.0 Milliliters (mL)
Standard Deviation 372.32
|
1274.4 Milliliters (mL)
Standard Deviation 407.31
|
1221.0 Milliliters (mL)
Standard Deviation 278.07
|
1009.5 Milliliters (mL)
Standard Deviation 155.64
|
1201.0 Milliliters (mL)
Standard Deviation 355.73
|
|
Summary of Fluid Balance
Total Fluid Intake,0-24h
|
4196.3 Milliliters (mL)
Standard Deviation 1399.83
|
4210.0 Milliliters (mL)
Standard Deviation 1034.02
|
3934.7 Milliliters (mL)
Standard Deviation 762.13
|
4164.4 Milliliters (mL)
Standard Deviation 853.18
|
3998.2 Milliliters (mL)
Standard Deviation 1110.77
|
|
Summary of Fluid Balance
Total urine output,0-4h
|
1031.0 Milliliters (mL)
Standard Deviation 277.04
|
1107.0 Milliliters (mL)
Standard Deviation 294.54
|
1670.5 Milliliters (mL)
Standard Deviation 451.39
|
1546.5 Milliliters (mL)
Standard Deviation 593.86
|
1212.0 Milliliters (mL)
Standard Deviation 424.94
|
|
Summary of Fluid Balance
Total urine output,0-24h
|
4669.0 Milliliters (mL)
Standard Deviation 757.00
|
4421.0 Milliliters (mL)
Standard Deviation 741.14
|
5168.0 Milliliters (mL)
Standard Deviation 1212.52
|
5004.0 Milliliters (mL)
Standard Deviation 884.00
|
4941.0 Milliliters (mL)
Standard Deviation 962.68
|
|
Summary of Fluid Balance
Fluid Balance,0-4h
|
209.0 Milliliters (mL)
Standard Deviation 352.43
|
167.4 Milliliters (mL)
Standard Deviation 468.47
|
-449.5 Milliliters (mL)
Standard Deviation 533.77
|
-537.0 Milliliters (mL)
Standard Deviation 607.98
|
-11.0 Milliliters (mL)
Standard Deviation 541.71
|
|
Summary of Fluid Balance
Fluid Balance,0-24h
|
-472.7 Milliliters (mL)
Standard Deviation 1076.26
|
-211.0 Milliliters (mL)
Standard Deviation 984.94
|
-1233.3 Milliliters (mL)
Standard Deviation 841.19
|
-839.6 Milliliters (mL)
Standard Deviation 772.69
|
-942.8 Milliliters (mL)
Standard Deviation 513.29
|
PRIMARY outcome
Timeframe: Up to 24 hours post dose of each treatment period.Population: Safety Population.
The plasma measurements at specified time points on Day 1 were collected. Derived plasma glucose parameters were presented.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Mean of Derived Plasma Glucose Parameters
Pre-Dose
|
5.75639 mmol/L
Standard Deviation 1.285496
|
6.65953 mmol/L
Standard Deviation 1.165222
|
6.18659 mmol/L
Standard Deviation 1.696588
|
5.72419 mmol/L
Standard Deviation 0.850452
|
5.86796 mmol/L
Standard Deviation 0.881584
|
|
Mean of Derived Plasma Glucose Parameters
2 h
|
18.26279 mmol/L
Standard Deviation 2.222558
|
13.70542 mmol/L
Standard Deviation 4.831705
|
16.11455 mmol/L
Standard Deviation 3.711572
|
14.76566 mmol/L
Standard Deviation 2.542980
|
15.00435 mmol/L
Standard Deviation 3.158931
|
|
Mean of Derived Plasma Glucose Parameters
4 h
|
15.31521 mmol/L
Standard Deviation 3.646185
|
9.47778 mmol/L
Standard Deviation 4.288005
|
11.52943 mmol/L
Standard Deviation 3.154919
|
10.68068 mmol/L
Standard Deviation 3.161241
|
11.04094 mmol/L
Standard Deviation 3.184558
|
|
Mean of Derived Plasma Glucose Parameters
6 h
|
19.53952 mmol/L
Standard Deviation 4.101401
|
9.91464 mmol/L
Standard Deviation 3.978186
|
16.02019 mmol/L
Standard Deviation 4.685123
|
14.97660 mmol/L
Standard Deviation 5.647356
|
15.50949 mmol/L
Standard Deviation 4.792842
|
|
Mean of Derived Plasma Glucose Parameters
8 h
|
18.01300 mmol/L
Standard Deviation 5.158167
|
8.87790 mmol/L
Standard Deviation 2.958162
|
14.21611 mmol/L
Standard Deviation 5.359803
|
13.69432 mmol/L
Standard Deviation 6.375146
|
14.47146 mmol/L
Standard Deviation 5.477677
|
|
Mean of Derived Plasma Glucose Parameters
12 h
|
14.67129 mmol/L
Standard Deviation 6.061024
|
11.34791 mmol/L
Standard Deviation 3.897886
|
12.95048 mmol/L
Standard Deviation 4.566692
|
11.31849 mmol/L
Standard Deviation 3.376891
|
11.87914 mmol/L
Standard Deviation 4.053962
|
SECONDARY outcome
Timeframe: Up to 24 hours post dose of each treatment period.Population: Safety Population
AUC(0-10) was the plasma glucose weighted mean AUC for 0 to 10 h post-dosing and AUC(0-4) was the plasma glucose weighted mean AUC for 0 to 4 h post-dosing. Incremental Adjusted Weighted Means were presented.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1
AUC(0-4)
|
8.739 mmol/L
Standard Deviation 2.4304
|
4.480 mmol/L
Standard Deviation 2.9942
|
6.632 mmol/L
Standard Deviation 2.0126
|
6.044 mmol/L
Standard Deviation 1.9444
|
6.099 mmol/L
Standard Deviation 2.3135
|
|
Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1
AUC(0-10)
|
10.535 mmol/L
Standard Deviation 3.8388
|
3.127 mmol/L
Standard Deviation 2.2467
|
7.112 mmol/L
Standard Deviation 3.3103
|
6.653 mmol/L
Standard Deviation 3.2809
|
7.054 mmol/L
Standard Deviation 3.5440
|
SECONDARY outcome
Timeframe: Up to 24 hours post dose of each treatment periodPopulation: Safety Population
UGE was assessed for timed subintervals up to 24h post-dose. Urine samples were collected at intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h on study days. The 0-24h amounts excreted in urine were calculated by adding the amounts collected during these time intervals.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Urinary Glucose Excretion (UGE) for Timed Subintervals up to 24 Hours Post Dose (0-24 H)
|
324.849 mmol
Standard Deviation 252.6604
|
135.119 mmol
Standard Deviation 191.6857
|
579.060 mmol
Standard Deviation 227.9230
|
601.879 mmol
Standard Deviation 206.4860
|
770.249 mmol
Standard Deviation 245.1817
|
SECONDARY outcome
Timeframe: Up to 24 hours post dose of each treatment period.Population: Safety Population
Filtered glucose in the urine was assessed at indicated time points and was presented as Percentage. The 0-12h and 0-24h amounts Percent of filtered glucose in the urine were calculated by adding the amounts collected during these time intervals.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Percent of Filtered Glucose in the Urine.
0-4 H
|
10.8661 Percentage
Standard Deviation 6.21239
|
6.5576 Percentage
Standard Deviation 5.24295
|
40.4788 Percentage
Standard Deviation 7.00049
|
41.5290 Percentage
Standard Deviation 14.95891
|
41.3449 Percentage
Standard Deviation 12.49532
|
|
Percent of Filtered Glucose in the Urine.
0-12 H
|
16.7543 Percentage
Standard Deviation 9.04186
|
7.0663 Percentage
Standard Deviation 8.62344
|
42.3900 Percentage
Standard Deviation 5.75325
|
47.5648 Percentage
Standard Deviation 10.41524
|
47.8442 Percentage
Standard Deviation 12.01952
|
|
Percent of Filtered Glucose in the Urine.
0-24 H
|
11.1012 Percentage
Standard Deviation 5.76206
|
5.6518 Percentage
Standard Deviation 5.12934
|
25.4355 Percentage
Standard Deviation 4.74207
|
29.9386 Percentage
Standard Deviation 5.99518
|
34.5245 Percentage
Standard Deviation 10.00663
|
SECONDARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
Urine volume was recorded over intervals : 0-4h, 4-8h, 8-12h, 12-16h and 16- 24h on Day 1 for each dosing period. Mean total Urine volume over 24 hours was presented.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Mean Total Urine Volume 0-24 H
|
4628.5 mL
Standard Deviation 746.74
|
4623.0 mL
Standard Deviation 828.93
|
5267.5 mL
Standard Deviation 1077.76
|
4962.0 mL
Standard Deviation 885.86
|
5274.4 mL
Standard Deviation 899.07
|
SECONDARY outcome
Timeframe: Day 1 of each treatment periodPopulation: Safety Population
Urine samples for calculating creatinine clearance were obtained over the intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. Mean creatinine clearance over 0-24 H was presented.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Mean Creatinine Clearance 0-24 H
|
113.6 mL/min
Standard Deviation 30.30
|
124.0 mL/min
Standard Deviation 35.48
|
120.9 mL/min
Standard Deviation 30.05
|
121.3 mL/min
Standard Deviation 38.01
|
128.2 mL/min
Standard Deviation 26.45
|
SECONDARY outcome
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 periodPopulation: Safety Population
AUC(0-last) was defined as area under the plasma concentration vs. time curve from time zero (time of dosing) to the last time point with measurable analyte concentration and AUC(0-inf) was defined as area under the plasma concentration vs. time curve from time zero to infinite time. Blood samples were collected on time points: 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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
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
AUC(0-inf)
|
8.101 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 24
|
25.922 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 38
|
58.362 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 60
|
—
|
—
|
|
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
AUC(0-last)
|
3.966 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 95
|
16.552 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 57
|
47.390 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 67
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Safety Population
Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as Geometric Means with respective Geometric Coefficient of Variation (% CV).
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of GSK189075 Over Period
|
5.266 ng/mL
Geometric Coefficient of Variation 90
|
11.903 ng/mL
Geometric Coefficient of Variation 92
|
39.029 ng/mL
Geometric Coefficient of Variation 128
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Safety Population. Only those participants available at specified time points were analyzed.
Tmax was defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. T1/2 was defined as the time to when half of the total amount of a particular substance is eliminated from the body. Blood samples obtained during indicated time points. T1/2 was calculated as t1/2 = ln2/λz, with λz (the terminal elimination rate-constant) estimated from log-linear regression analysis of the terminal phase of the plasma concentration-time profile.Tmax and t1/2 values for GSK189075 were presented.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period
Tmax
|
0.446 hour
Geometric Coefficient of Variation 68
|
0.521 hour
Geometric Coefficient of Variation 81
|
1.054 hour
Geometric Coefficient of Variation 145
|
—
|
—
|
|
Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period
t1/2
|
0.915 hour
Geometric Coefficient of Variation 20
|
1.019 hour
Geometric Coefficient of Variation 41
|
0.678 hour
Geometric Coefficient of Variation 29
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Safety Population
AUC(0-4) was defined as AUC from time zero to 4 hours post dose. Blood samples were collected on time points: 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.
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
AUC From Time Zero to 4 Hours Post Dose, AUC(0-4) for GSK189074 Over Period
|
243.281 hr*ng/mL
Geometric Coefficient of Variation 34
|
700.970 hr*ng/mL
Geometric Coefficient of Variation 38
|
2038.298 hr*ng/mL
Geometric Coefficient of Variation 34
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Safety Population
Oral clearance is a measure of the rate at which the drug is cleared from the body via metabolism. Blood samples were collected on time points: 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
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Oral Clearance (CL/F) Over Period
|
2849.947 mL/min
Geometric Coefficient of Variation 36
|
2732.322 mL/min
Geometric Coefficient of Variation 41
|
2903.590 mL/min
Geometric Coefficient of Variation 37
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Safety Population
Blood samples were collected on time points: 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 to obtain the metabolite to parent AUC ratio for GSK189074
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK189074 Over Period
|
90.436 Ratio
Geometric Coefficient of Variation 70
|
67.801 Ratio
Geometric Coefficient of Variation 36
|
74.281 Ratio
Geometric Coefficient of Variation 52
|
—
|
—
|
SECONDARY outcome
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 periodPopulation: Pharmacokinetic (PK) Parameter Population comprised of all participants for whom pharmacokinetic parameter estimates were derived during any treatment period
Blood samples were collected on time points: 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 to obtain the metabolite to parent AUC ratio for GSK279782
Outcome measures
| Measure |
Placebo
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
|
Placebo+ Prandial Insulin
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 Participants
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK279782 Over Period
|
0.427 Ratio
Geometric Coefficient of Variation 58
|
0.442 Ratio
Geometric Coefficient of Variation 60
|
0.433 Ratio
Geometric Coefficient of Variation 55
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo+ Prandial Insulin
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GSK189075 50mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
GSK189075 150mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
GSK189075 500mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=10 participants at risk
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
Placebo+ Prandial Insulin
n=10 participants at risk
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 50mg
n=10 participants at risk
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 150mg
n=10 participants at risk
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
GSK189075 500mg
n=10 participants at risk
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
Nervous system disorders
Headache
|
20.0%
2/10 • Approximately up to 6 months
Safety population was used.
|
20.0%
2/10 • Approximately up to 6 months
Safety population was used.
|
30.0%
3/10 • Approximately up to 6 months
Safety population was used.
|
20.0%
2/10 • Approximately up to 6 months
Safety population was used.
|
20.0%
2/10 • Approximately up to 6 months
Safety population was used.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
General disorders
Catheter site related reaction
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
General disorders
Discomfort
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
10.0%
1/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
0.00%
0/10 • Approximately up to 6 months
Safety population was used.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER