Trial Outcomes & Findings for Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 in Type 2 Diabetes Patients Taking Metformin (NCT NCT01929863)
NCT ID: NCT01929863
Last Updated: 2017-08-16
Results Overview
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.
COMPLETED
PHASE2
16 participants
Up to Follow-up (up to 53 days)
2017-08-16
Participant Flow
The study was planned on 16 participants with Type 2 diabetes mellitus (T2DM), aged 30 to 64 years, at a single center of United States from 22 August 2013 to 21 November 2013.
A total of 15 participants were randomized in the study and entered a run-in period where participants were administered oral dose of metformin 850 milligram (mg) tablet twice daily (BID) for 14 days, after which they entered the 2 double blind treatment periods in a crossover manner.
Participant milestones
| Measure |
Metformin and GSK2330672, Then Placebo and Metformin
Participants received oral dose of treatment A-metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 according to a plan of randomization. After a washout period of 13 to 15 days, participants received oral dose of treatment B-metformin 850 mg tablet BID plus matching placebo to GSK2330672 tablet BID for 7 days. During the washout period, participants received metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Placebo and Metformin, Then Metformin and GSK2330672
Participants received oral dose of treatment B-metformin 850 mg tablet BID plus matching placebo to GSK2330672 tablet BID for 7 days according to a plan of randomization. After a washout period of 13 to 15 days, participants received oral dose of treatment A-metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7. During the washout period, participants received metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|
|
Period 1:Intervention Period 1 (7 Days)
STARTED
|
7
|
8
|
|
Period 1:Intervention Period 1 (7 Days)
COMPLETED
|
6
|
7
|
|
Period 1:Intervention Period 1 (7 Days)
NOT COMPLETED
|
1
|
1
|
|
Period 2:Washout Period (13-15 Days)
STARTED
|
6
|
7
|
|
Period 2:Washout Period (13-15 Days)
COMPLETED
|
6
|
7
|
|
Period 2:Washout Period (13-15 Days)
NOT COMPLETED
|
0
|
0
|
|
Period 3:Intervention Period 2 (7 Days)
STARTED
|
6
|
7
|
|
Period 3:Intervention Period 2 (7 Days)
COMPLETED
|
6
|
6
|
|
Period 3:Intervention Period 2 (7 Days)
NOT COMPLETED
|
0
|
1
|
|
Period 4:Follow-up-Metformin (7-10 Days)
STARTED
|
6
|
6
|
|
Period 4:Follow-up-Metformin (7-10 Days)
COMPLETED
|
0
|
0
|
|
Period 4:Follow-up-Metformin (7-10 Days)
NOT COMPLETED
|
6
|
6
|
Reasons for withdrawal
| Measure |
Metformin and GSK2330672, Then Placebo and Metformin
Participants received oral dose of treatment A-metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 according to a plan of randomization. After a washout period of 13 to 15 days, participants received oral dose of treatment B-metformin 850 mg tablet BID plus matching placebo to GSK2330672 tablet BID for 7 days. During the washout period, participants received metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Placebo and Metformin, Then Metformin and GSK2330672
Participants received oral dose of treatment B-metformin 850 mg tablet BID plus matching placebo to GSK2330672 tablet BID for 7 days according to a plan of randomization. After a washout period of 13 to 15 days, participants received oral dose of treatment A-metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7. During the washout period, participants received metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|
|
Period 1:Intervention Period 1 (7 Days)
Adverse Event
|
1
|
0
|
|
Period 1:Intervention Period 1 (7 Days)
Withdrawal by Subject
|
0
|
1
|
|
Period 3:Intervention Period 2 (7 Days)
Adverse Event
|
0
|
1
|
Baseline Characteristics
Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 in Type 2 Diabetes Patients Taking Metformin
Baseline characteristics by cohort
| Measure |
All Study Participants
n=15 Participants
In each treatment period, participants received oral dose of treatment A-metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 or oral dose of treatment B-metformin 850 mg tablet BID plus matchig placebo to GSK2330672 tablet BID for 7 days according to a plan of randomization. The two treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|
|
Age, Continuous
|
54.9 Years
STANDARD_DEVIATION 7.06 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population was defined as all participants enrolled into the study who have received at least one dose of study drug (including metformin, GSK2330672, and matching placebo. One participant withdrew consent after taking period 1 study treatment of placebo + GSK2330672.
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE) or Death
Any AE
|
12 Participants
|
9 Participants
|
—
|
|
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE) or Death
Any SAE
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE) or Death
Any Death
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population.
The assessments were done at Day -1, Day 3, Day 8 and Follow-up under fasting condition. The following laboratory parameters of clinical chemistry were analyzed: blood urea nitrogen (BUN), creatinine, fasting triglycerides (TGs), total cholesterol, low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), sodium, potassium, chloride, total bicarbonate, calcium, aspartate aminotransferase (AST), ALT, gamma glutamyltransferase (GGT), alkaline phosphatase, total and direct bilirubin, uric acid, albumin and total protein. Baseline was the assessment done on Day -1 (pre dose). Only those parameters for which at least one value of PCI was reported are summarized. Data is reported for participants with high glucose PCI, where the PCI value for T2DM participants was ( low \< 3.8857 millimole per liter (mmol/L); high \> 15 mmol/L; normal range was 3.61 - 5.5 mmol/L).
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Importance (PCI) at Any Time Post Baseline
|
0 Participants
|
0 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population.
The assessments were done at Day -1, Day 3, Day 8 and Follow-up under fasting condition. The following laboratory parameters of clinical haematology were analyzed: platelet count, red blood cells (RBC) count, absolute white blood cells (WBC) count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was the assessment done on Day -1 (pre dose). Only those parameters for which at least one value of PCI was reported are summarized. Data is reported for participants with high WBC counts PCI, where the PCI value for T2DM participants was (relative low : 0.5 multiplier of lower limit of normal \[LLN\]; relative high : 1.82 multiplier of upper limit of normal \[LLN\]; where normal range was 3.8 - 10.8 giga cells per liter (GI/L).
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With the Indicated Haematology Values of PCI at Any Time Post Baseline
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population.
The assessments were done at Day -1, Day 3, Day 8 and Follow-up under fasting condition for microscopic analysis of bacteria, hyaline casts (semi-quantitive), RBC, squamous epithelial cells and WBC. Baseline was the assessment done on Day -1 (pre dose). The participants were categorized as 0-5, 6-10, 10-20, moderate, few and many. Only those parameters for which at least one value of these categories reported are summarized.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, Bacteria, Day 3, Few
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, Bacteria, Day 3, Many
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, Bacteria, Day 8, Few
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, Bacteria, Follow-up, Many
|
—
|
—
|
1 Participants
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, SEC's, Day 3, 0-5
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, SEC's, Day 8, 0-5
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, SEC's, Follow-up, 0-5
|
—
|
—
|
1 Participants
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, SEC's, Follow-up, 6-10
|
—
|
—
|
1 Participants
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, WBC's, Day 3, 10-20
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, WBC's, Follow-up, 0-5
|
—
|
—
|
1 Participants
|
|
Number of Participants With Abnormal Values of Urine Microscopic Analysis of Bacteria, Hyaline Casts (Semi-quantitive), RBC, Squamous Epithelial Cells and WBC at Any Time Post Baseline
Urine Microscopy, WBC's, Follow-up, 6-10
|
—
|
—
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety population.
The assessments were done at Day -1, Day 3, Day 8 and Follow-up under fasting condition for urine dipstic analysis of occult blood, glucose, ketones and proteins. Baseline was the assessment done on Day -1 (pre dose). The participants were categorized with results of 1+, 2+, 3+ and trace. Only those parameters for which at least one value of these categories reported are summarized.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Day 3, 1+
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Day 3, 2+
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Day 3, Trace
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Day 8, 2+
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Day 8, Trace
|
2 Participants
|
5 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Follow-up, 3+
|
—
|
—
|
3 Participants
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Glucose, Follow-up, Trace
|
—
|
—
|
3 Participants
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Ketones, Day 3, Trace
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Ketones, Follow-up, Trace
|
—
|
—
|
2 Participants
|
|
Number of Participants With Abnormal Values of Urine Dipstic Analysis of Occult Blood, Glucose, Ketones and Proteins at Any Visit Post Baseline
Urine Protein, Follow-up, Trace
|
—
|
—
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population. Only those participants available at the specified time points were analyzed.
Urine specific gravity is a laboratory test that shows the concentration of all chemical particles in the urine. The assessments were done at Day -1, Day 3, Day 8 and Follow-up under fasting condition. Baseline was the assessment done on Day -1 (pre dose).
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Mean Specific Gravity of Urine at Any Visit Post Baseline
Day 8
|
1.0125 Ratio
Standard Deviation 0.00654
|
1.0109 Ratio
Standard Deviation 0.00386
|
—
|
|
Mean Specific Gravity of Urine at Any Visit Post Baseline
Day 3
|
1.0121 Ratio
Standard Deviation 0.00352
|
1.0110 Ratio
Standard Deviation 0.00335
|
—
|
|
Mean Specific Gravity of Urine at Any Visit Post Baseline
Follow-up
|
—
|
—
|
1.0203 Ratio
Standard Deviation 0.00832
|
PRIMARY outcome
Timeframe: Day 8 of both treatment periodsPopulation: Safety Population.
The assessment of fecal occult blood was done on Day 8. Stool sample was obtained any time after dosing on Day 7.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With Abnormal Results for Fecal Occult Blood Test
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population.
Vital signs assessment included heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Assessments were completed at pre morning dose on Day 1 (Baseline), Day 3, Day 8 (before discharge) and Follow-up. Criteria for vital sign values meeting PCI for Type 2 diabetes mellitus (T2DM) included: SBP \<85 and \>160 millimeters of mercury (mmHg), DBP \<45 and \>100 mmHg and HR \<40 and \>110 beats per minute (bpm). Only those parameters for which at least one value of PCI was reported are summarized.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With Vital Sign Values of PCI at Any Time Post Baseline
SBP
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Vital Sign Values of PCI at Any Time Post Baseline
HR
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (up to 53 days)Population: Safety Population. Only those participants available at the specified time points were analyzed.
12-lead ECG assessments were obtained pre-dose at Day 1, Day 3, Day 8 (before discharge) and Follow-up. The assessments were done using an ECG machine that automatically calculated the heart rate and measures PQ, QRS, QT, and QTc(B) intervals. Abnormal ECG findings (clinically significant or not clinically significant) were categorized. The abnormal PCI range for T2DM participants include QTc interval of \>450 to \<=480 milliseconds (msec) and increase from Baseline QTc interval of \> 30 to \<=60 msec, PR interval \<110 and \>220 msec and QRS interval \<75 and \>110 msec. ECG abnormalities were categorized as clinically significant or not clinically significant based on PCI criteria and judgment of the investigator. Baseline was defined as the mean of three replicate assessments at pre-dose on Day 1.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
n=15 Participants
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Not-clinically Significant, Day 3
|
3 Participants
|
2 Participants
|
—
|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Clinically Significant, Day 3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Not-clinically Significant, Day 8
|
2 Participants
|
4 Participants
|
—
|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Clinically Significant, Day 8
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Not-clinically Significant, Follow-up
|
—
|
—
|
3 Participants
|
|
Number of Participants With Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Time Post Baseline
Clinically Significant, Follow-up
|
—
|
—
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 to 7 of each treatment periodPopulation: Safety Population.
The BSFR Scale assessed stool quality using a 7-point scale, where 1=separate hard lumps like nuts (difficult to pass) and 7=watery, no solid pieces (entirely liquid). Bristol Stool Form Scale Rating: 1=separate hard lumps, like nuts, 2=sausage shaped but lumpy, 3=like a sausage or snake but with cracks on its surface, 4=like a sausage or snake, smooth and soft, 5=soft blobs with clear cut edges, 6=fluffy pieces with ragged edges, a mushy stool, 7=watery, no solid pieces. Data is reported for number of events in participants with each category of BSFR scale across Day 1 to 7 post morning dose.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 1
|
0 Number of events
|
6 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 2
|
4 Number of events
|
4 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 3
|
4 Number of events
|
8 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 4
|
11 Number of events
|
20 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 5
|
18 Number of events
|
15 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 6
|
60 Number of events
|
17 Number of events
|
—
|
|
Number of Events of Stool or Bowel Movements of Participants Using Bristol Stool Form Rating (BSFR) Scale Across Day 1 to 7
Participants with Rating 7
|
111 Number of events
|
16 Number of events
|
—
|
PRIMARY outcome
Timeframe: Day 1 to 7 of each treatment periodPopulation: Safety Population.
The BSFR Scale assessed stool quality using a 7-point scale, where 1=separate hard lumps like nuts (difficult to pass) and 7 = watery, no solid pieces (entirely liquid). Bristol Stool Form Scale Rating: 1=separate hard lumps, like nuts, 2=sausage shaped but lumpy, 3=like a sausage or snake but with cracks on its surface, 4=like a sausage or snake, smooth and soft, 5=soft blobs with clear cut edges, 6=fluffy pieces with ragged edges, a mushy stool, 7=watery, no solid pieces. Data is reported for number of events in participants with each category of BSFR scale across Day 1 to 7 post morning dose.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 1
|
0 Participants
|
4 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 2
|
3 Participants
|
3 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 3
|
4 Participants
|
6 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 4
|
5 Participants
|
10 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 5
|
8 Participants
|
6 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 6
|
12 Participants
|
8 Participants
|
—
|
|
Number of Participants in Each Category of BSFR Across Day 1 to 7
Rating 7
|
14 Participants
|
6 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and Day 8 of each treatment periodPopulation: Safety Population.
The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS is the mean of questions 1-15 and range from 1 to 7, with lower scores indicating a better quality of life with respect to gastrointestinal symptoms. Baseline was defined as the assessment done on Day -1. Change from baseline was calculated by subtracting the baseline (Day -1) values from the post-baseline value (Day 8).
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=12 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Mean Change From Baseline in Overall Gastrointestinal Symptom Rating Scale (GSRS) Scores
|
0.59 Score on scale
Standard Deviation 0.891
|
0.08 Score on scale
Standard Deviation 0.468
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 7 of each treatment periodPopulation: Safety Population. Only those participants available at the specified time points were analyzed.
Baseline was defined as the time matched assessment done on Day -1. Change from baseline was calculated by subtracting the baseline (Day -1) time matched values from the post-baseline value (Day 8). Data is reported for fasting glucose level and for weighted mean and maximum values for fasting, 0-4 h, 4-10 h, 10-14 h and 0-24 h. Area under the curve (AUC) with respect to these time interval was calculated using the linear trapezoidal rule by the sum of the areas between each chronological pair of assessments (using observed times). The weighted mean was then determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in h). Analysis was done using analysis of covariance (ANCOVA) model where, change from baseline was summation of baseline, period, sequence and treatment. Participants were fitted as a random effect.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=12 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
Fasting Value
|
-12.325 mg/deciliter
Standard Deviation 36.1277
|
7.479 mg/deciliter
Standard Deviation 44.6181
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
Maximum (0-4 h)
|
6.250 mg/deciliter
Standard Deviation 45.2270
|
22.857 mg/deciliter
Standard Deviation 49.1307
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
Maximum (4-10 h)
|
-6.583 mg/deciliter
Standard Deviation 45.4402
|
29.714 mg/deciliter
Standard Deviation 42.1251
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
Maximum (10-14 h)
|
2.500 mg/deciliter
Standard Deviation 51.34819
|
40.307 mg/deciliter
Standard Deviation 56.18196
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
Maximum (0-24 h)
|
4.583 mg/deciliter
Standard Deviation 45.9020
|
23.071 mg/deciliter
Standard Deviation 39.6959
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
AUC (0-4 h) Weighted Mean
|
6.0737 mg/deciliter
Standard Deviation 43.37336
|
22.0247 mg/deciliter
Standard Deviation 46.54980
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
AUC (4-10 h) Weighted Mean
|
-4.6051 mg/deciliter
Standard Deviation 43.31083
|
24.7262 mg/deciliter
Standard Deviation 39.21502
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
AUC (10-14 h) Weighted Mean
|
4.4221 mg/deciliter
Standard Deviation 55.00201
|
38.2479 mg/deciliter
Standard Deviation 51.91011
|
—
|
|
Maximum and Weighted Mean Change From Baseline in Plasma Glucose Concentrations Over a 24 Hour (h) Period on Day 7
AUC (0-24 h) Weighted Mean
|
-2.0829 mg/deciliter
Standard Deviation 44.76645
|
26.0704 mg/deciliter
Standard Deviation 40.74711
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 h), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7 of each treatment periodPopulation: Pharmacokinetic (PK) Population was defined as participants from the safety population who had plasma metformin and or GSK2330672 PK parameter estimates from any portion of the study. Only those participants available at the specified time points were analyzed.
AUC(0-10) for metformin when co-dosed with GSK2330672 or placebo is defined as the the area under the plasma concentration-time curve from time 0 to 10 h. It was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at 0 h (pre-dose within 15 min of dose and began eating breakfast immediately after taking study drug and finished eating in 15 min), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7. Analysis was done using a mixed effects model with fixed effect terms for treatment, period, and sequence. Participant within sequence was fitted as a random effect in the model.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=12 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
AUC From Time 0 to 10 h (AUC 0-10 h) of Metformin in Presence of GSK2330672 or Placebo on Day 7
|
9189.2649 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 34.080
|
9232.5372 Nanogram (ng)*h/mL
Geometric Coefficient of Variation 24.404
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 h), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7 of each treatment periodPopulation: PK Population. Only those participants available at the specified time points were analyzed.
Cmax is defined as the first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data Blood samples were collected at 0 h (pre-dose within 15 min of dose and began eating breakfast immediately after taking study drug and finished eating in 15 min), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7. Analysis was done using a mixed effects model with fixed effect terms for treatment, period, and sequence. Participant within sequence was fitted as a random effect in the model.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=12 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Maximum Plasma Concentration of Metformin (Cmax) in Presence of GSK2330672 or Placebo on Day 7
|
1707.1 ng/mL
Geometric Coefficient of Variation 28
|
1638.3 ng/mL
Geometric Coefficient of Variation 25
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 h), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7 of each treatment periodPopulation: PK Population. Only those participants available at the specified time points were analyzed.
Tmax is defined as the time at which Cmax is observed, determined directly from the raw concentration-time data. Blood samples were collected at 0 h (pre-dose within 15 min of dose and began eating breakfast immediately after taking study drug and finished eating in 15 min), 0.25 h, 0.50 h, 1 h, 2 h, 3 h, 4 h (pre-lunch), 5 h, 5.5 h, 6 h, 8 h and 10 h (pre-dinner) on Day 7.
Outcome measures
| Measure |
Treatment A-GSK2330672 + Metformin
n=12 Participants
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Treatment B-Placebo + Metformin
n=14 Participants
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
Follow-up-Metformin
After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|---|
|
Median Time to Observed Peak Plasma Concentration (Tmax) When Co-dosed With GSK2330672 or Placebo on Day 7
|
1.4583 h
Interval 0.5 to 2.0
|
1.0000 h
Interval 1.0 to 2.0
|
—
|
Adverse Events
Treatment A-GSK2330672 + Metformin
Treatment B-Placebo + Metformin
Serious adverse events
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 participants at risk
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up
|
Treatment B-Placebo + Metformin
n=14 participants at risk
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|
|
Hepatobiliary disorders
Cholecystitis acute
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
Other adverse events
| Measure |
Treatment A-GSK2330672 + Metformin
n=14 participants at risk
Participants received oral dose of metformin 850 mg BID tablet for 7 days plus GSK2330672 45 mg tablet BID on Day 1 and 2 and GSK2330672 90 mg tablet BID on Day 3 to 7 in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up
|
Treatment B-Placebo + Metformin
n=14 participants at risk
Participants received oral dose of metformin 850 mg tablet BID for 7 days plus matching placebo to GSK2330672 tablet BID for 7 days in a sequence of treatment A/B or B/A according to a plan of randomization. Treatment periods were separated by a washout period of 13 to 15 days in which participants continued metformin 850 mg tablet BID. After completion of the double blind treatment period 2 (after the last dose of period 2), participants received oral dose of metformin 850 mg tablet BID for 7-10 days of Follow-up.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
78.6%
11/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
50.0%
7/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
2/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
2/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Nervous system disorders
Headache
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
21.4%
3/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
General disorders
Pyrexia
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
|
Investigations
Blood glucose increased
|
0.00%
0/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
7.1%
1/14 • AE's and SAE's were collected from the start of study treatment of metformin in the run-in period and until Follow-up (up to 53 days)
Safety Population was used.
|
Additional Information
GSK Response Center
GlaxoSmithKline
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