A Study to Investigate the Safety, Tolerability, Pharmaco... | NCT01218204 | Trialant
NCT01218204
Sponsor
GlaxoSmithKline
Status
Completed
Last Update Posted
Jul 16, 2019Actual
Enrollment
287Actual
Phase
Phase 2
Conditions
Dyslipidaemias
Dyslipidemias
Interventions
10mg atorvastatin
80mg atorvastatin
GSK1292263 Placebo
100mg GSK1292263
300mg GSK1292263
800mg GSK1292263
10mg ezetimibe
Washout
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT01218204
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
113779
Secondary IDs
Not provided
Brief Title
A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin
Official Title
A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
Jun 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 14, 2010Actual
Primary Completion Date
Jun 29, 2011Actual
Completion Date
Jun 29, 2011Actual
First Submitted Date
Sep 23, 2010
First Submission Date that Met QC Criteria
Oct 7, 2010
First Posted Date
Oct 11, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 31, 2017
Results First Submitted that Met QC Criteria
Oct 9, 2017
Results First Posted Date
Nov 8, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Apr 27, 2015
Certification/Extension First Submitted that Passed QC Review
Apr 27, 2015
Certification/Extension First Posted Date
May 13, 2015Estimated
Last Update Submitted Date
Jul 5, 2019
Last Update Posted Date
Jul 16, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
GlaxoSmithKlineINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia.
Detailed Description
This compound has been studied in healthy subjects and subjects with type II diabetes and is now being studied in subjects with dyslipidemia. Because many patients with dyslipidemia are on statins, it is important to study how GSK1292263 behaves when taken with a potent statin, atorvastatin. The cholesterol lowering drug, ezetimibe, is included for comparison.
Conditions Module
Conditions
Dyslipidaemias
Dyslipidemias
Keywords
Pharmacodynamics
Lipids
Dyslipidemia
Safety
GSK1292263
Ezetimibe
Statin
Pharmacokinetics
Tolerability
Atorvastatin
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
287Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A Run-in
Other
Subjects on stable 40mg atorvastatin > 4 weeks may raise their dose to 80mg for 2 weeks in order to qualify for Part A.
Drug: 80mg atorvastatin
Part A Co-Dosing 800mg GSK1292263
Experimental
Dosing for 14 days
Drug: 800mg GSK1292263
Part B Washout
Other
Washout for 4 weeks
Other: Washout
Part B Run-in 10mg atorvastatin
Active Comparator
Dosing for 4 weeks
Drug: 10mg atorvastatin
Part B Run-in 80mg atorvastatin
Active Comparator
Dosing for 4 weeks
Drug: 80mg atorvastatin
Part B Co-Dosing 10mg atorvastatin + 100mg GSK1292263
Experimental
Dosing for 14 days
Interventions
Name
Type
Description
Arm Group Labels
Other Names
10mg atorvastatin
Drug
10mg
Part B Co-Dosing 10mg atorvastatin + 100mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe
Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Up to Day 26
Number of Participants With Any AEs and SAEs- Part B (Washout)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Up to Day 28
Number of Participants With Any AEs and SAEs- Part B (Run-in)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Secondary Outcomes
Measure
Description
Time Frame
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who is capable of giving informed consent.
A female subject is eligible to participate if she is of:
Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory in the absence of a clear post-menopausal history.
Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study.
Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until seven days following the last dose.
Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0 (inclusive).
Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for >= 4 weeks and are tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a fasting low density lipoprotein cholesterol (LDLc) >= 130mg/dL.
In Part B at Screening: Subjects who are on statins or Vytorin treatment for >= 4 weeks.
Part B at the end of the 4 week washout: Subjects who have a fasting LDL cholesterol of >=120mg/dL and <=180mg/dL and fasting triglycerides of >=100mg/dL and <=400mg/dL.
Part B at the end of the 4 week run-in on atorvastatin: Subjects who are tolerating well atorvastatin 10mg or 80mg (as determined by the Investigator).
Part B: Subjects must be willing to discontinue statins or Vytorin for the duration of the study.
Liver enzymes, AST and ALT < 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin =< 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Subjects with Gilbert's syndrome are allowed to participate in the study.
Average QTcB or QTcF < 450msec; or QTc < 480msec in subjects with right bundle branch block.
Exclusion Criteria:
A medical history of the following:
Clinical or angiographic cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease (including stroke and transient ischemic attack [mini-stroke]), peripheral vascular disease. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
Homozygous familial hypercholesterolemia or family history of familial hypercholesterolemia (Part B only). Note: Subjects with heterozygous familial hypercholesterolemia on 80mg atorvastatin who are tolerating this drug well and fulfill the other eligibility criteria may participate in Part A only.
History of recurrent or unexplained muscle aches (e.g., fibromyalgia), myopathy or myositis, whether or not it is related to treatment with statins or other lipid modifying drugs.
Renal impairment as defined by a calculated glomerular filtration rate < 60 mL/min
History of diabetes mellitus, or history of post-prandial and/or random blood glucose > 200 mg/dl or fasting glucose > 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g., thiazolidinediones, sulfonylureas, insulin, metformin).
History of pancreatitis within 10 years of screening.
Any concurrent serious illness (e.g., severe chronic obstructive pulmonary disease, sleep apnea, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Active peptic ulcer disease and/or history of peptic ulcer disease or gastrointestinal bleeding within 12 months prior to screening.
History of kidney stones within 10 years of screening.
History of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by thyroid stimulating hormone (TSH) at Screening. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to screening and who have a screening TSH within the normal range may participate.)
Symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening.
Gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes within the past year.
Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs.
Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic.
Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic acid or fat absorption inhibitors are not eligible for Parts A and B.
For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.
Current inadequately controlled hypertension (blood pressure >= 160mmHg systolic or >= 100mmHg diastolic at screening). If blood pressure medication is changed as a result of screening, blood pressure will be re-measured after 6 weeks and must again meet these criteria.
Significant electrocardiogram (ECG) abnormalities, defined as follows:
Heart Rate < 50 and >100bpm PR Interval <120 and > 220ms QRS duration < 70 and >120ms QTC Interval (Bazett) > 450ms Or, has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment. Subjects with left bundle branch block are excluded from the study. Subjects with partial right bundle branch block may be considered for inclusion following consultation with the GlaxoSmithKline (GSK) Medical Monitor. Subjects with Wolf-Parkinson-White (WPW) syndrome are excluded from the study.
Creatinine phosphokinase (CPK) >= 2x ULN at screening.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for HIV antibody.
The subject has a positive pre-study drug-of-abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
Subjects will be excluded if they require treatment with systemic corticosteroids.
Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
History of sensitivity or untoward reaction to the study medications (GSK1292263, atorvastatin or ezetimibe), or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
History of intolerance to statins.
Any change in concomitant medication (including multivitamins, herbal remedies, dietary supplements, and over-the-counter medication) within six weeks prior to screening that is not approved by GSK.
On a diet that may affect study outcomes, or any change in diet, exercise habits or smoking status within six weeks prior to screening or planned change during study (e.g., new exercise program) other than that in the dietary instructions in the Study Procedures Manual.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
Where participation in study would result in donation of blood in excess of approximately 500mL within a 56 day period.
Subject is mentally or legally incapacitated.
Unwillingness or inability to follow the procedures outlined in the protocol.
Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
Lactating females.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
Unwilling to abstain from caffeine-or xanthine-containing products from Day -2 until Day 15.
Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
GSK Clinical Trials
GlaxoSmithKline
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
GSK Investigational Site
Anniston
Alabama
36207
United States
GSK Investigational Site
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Total 130 participants were randomized and received at least one dose of study drug in the treatment period phase. Part B Run-In excludes those participants randomized to monotherapy arms; that is, these participant counts are only those who were receiving Atorvastatin.
Recruitment Details
The study was conducted at 21 centers in the United States during the period 14 September 2010 to 29 June 2011. There were 6 total participants in Part A, then Part B started with total of 281 participants which flowed through the rest of the phases of the trial. Part B had washout phase and run-In phase followed by treatment phase.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A
Four participants on 80 milligrams (mg) atorvastatin [either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40mg], received GSK1292263 800 mg for 2 weeks, and 2 participants not on lipid-modifying treatment received GSK1282263 800 mg alone for 2 weeks.
FG001
Periods
Title
Milestones
Reasons Not Completed
Part A
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
Drug: 10mg atorvastatin
Part B Co-Dosing 10mg atorvastatin + 300mg GSK1292263
Experimental
Dosing for 14 days
Drug: 300mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263
Experimental
Dosing for 14 days
Drug: 10mg atorvastatin
Drug: 800mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe
Experimental
Dosing for 14 days
Drug: 10mg atorvastatin
Drug: 10mg ezetimibe
Part B Dosing 100mg GSK1292263
Experimental
Dosing for 14 days
Drug: 100mg GSK1292263
Part B Dosing 300mg GSK1292263
Experimental
Dosing for 14 days
Drug: 300mg GSK1292263
Part B Dosing 800mg GSK1292263
Experimental
Dosing for 14 days
Drug: 800mg GSK1292263
Part B Dosing Placebo GSK1292263
Experimental
Dosing for 14 days
Drug: GSK1292263 Placebo
Part B Co-Dosing 80mg atorvastatin + 800mg GSK1292263
Experimental
Dosing for 14 days
Drug: 80mg atorvastatin
Part B Co-dosing 80mg atorvastatin + Placebo (GSK1292263)
Experimental
Dosing for 14 days
Drug: GSK1292263 Placebo
Part B Co-Dosing 10mg atorvastatin + Placebo (GSK1292263)
Experimental
Dosing for 14 days
Drug: 10mg atorvastatin
Part B Co-Dosing 10mg atorvastatin + Placebo (GSK1292263)
Part B Run-in 10mg atorvastatin
Lipitor
80mg atorvastatin
Drug
80mg
Part A Run-in
Part B Co-Dosing 80mg atorvastatin + 800mg GSK1292263
Part B Run-in 80mg atorvastatin
Lipitor
GSK1292263 Placebo
Drug
Placebo
Part B Co-dosing 80mg atorvastatin + Placebo (GSK1292263)
Part B Dosing Placebo GSK1292263
100mg GSK1292263
Drug
100mg
Part B Dosing 100mg GSK1292263
300mg GSK1292263
Drug
300mg
Part B Co-Dosing 10mg atorvastatin + 300mg GSK1292263
Part B Dosing 300mg GSK1292263
800mg GSK1292263
Drug
800mg
Part A Co-Dosing 800mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263
Part B Dosing 800mg GSK1292263
10mg ezetimibe
Drug
10mg
Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe
Zetia
Washout
Other
No interventions - washout period
Part B Washout
Up to Day 28
Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Up to Day 26
Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A
Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.
Up to Day 26
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)
ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.
Up to Day 28
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)
ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.
Day 28
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)
Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.
Up to Day 26
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A
Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Up to Day 26
Number of Participants With Vital Signs of PCI- Part B (Washout)
Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Up to day 28
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)
Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Up to day 28
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)
Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Up to Day 26
Number of Participants With Abnormal Hematology Value of PCI- Part A
Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.
Up to Day 26
Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)
Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells [WBC], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.
Up to Day 28
Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)
Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.
Days 14 and 28
Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)
Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.
Up to Day 26
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A
Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.
Up to Day 26
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)
Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase [ALT], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate [CO2/HCO3] and Aspartate aminotransferase [AST]) are presented for which findings are of PCI either high or low.
Up to Day 28
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)
Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.
Days 14 and 28
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)
Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.
Up to Day 26
Maximum Observed Concentration (Cmax) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Cmax of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tlag of GSK1292263- Part B (Pooled Treatment Arm)
Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of GSK1292263
Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).
On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Cmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Cmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Tmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin- Part A
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of Atorvastatin
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Baseline and Day 14
Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Baseline and Day 14
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected.
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Chula Vista
California
91910
United States
GSK Investigational Site
Stockton
California
95204
United States
GSK Investigational Site
Jacksonville
Florida
32216
United States
GSK Investigational Site
Miami
Florida
33169
United States
GSK Investigational Site
Miami
Florida
33183
United States
GSK Investigational Site
Port Orange
Florida
32127
United States
GSK Investigational Site
St. Petersburg
Florida
33709
United States
GSK Investigational Site
Chicago
Illinois
60607
United States
GSK Investigational Site
Chicago
Illinois
60610
United States
GSK Investigational Site
Louisville
Kentucky
40213
United States
GSK Investigational Site
Kalamazoo
Michigan
49007
United States
GSK Investigational Site
Minneapolis
Minnesota
55430
United States
GSK Investigational Site
Berlin
New Jersey
08009
United States
GSK Investigational Site
Cincinnati
Ohio
45246
United States
GSK Investigational Site
Oklahoma City
Oklahoma
73112
United States
GSK Investigational Site
Eugene
Oregon
97404
United States
GSK Investigational Site
Spartanburg
South Carolina
29303
United States
GSK Investigational Site
San Antonio
Texas
78205
United States
GSK Investigational Site
San Antonio
Texas
78229
United States
GSK Investigational Site
Renton
Washington
98057
United States
Part B Washout
Participants were washed off their prior lipid-lowering therapy for 4 weeks.
FG002
Part B Run-in
Eligible participants were randomized to receive 10 mg open-labeled atorvastatin or 80 mg open-labeled atorvastatin for a 4-week stabilization run-in period.
FG003
Part B Pooled Treatment Arm
In this pooled arm, after washout, randomized participants were stratified into 11 arms to receive either atorvastatin 10 mg along with 100 mg or 300 mg or 800 mg of GSK129226 or placebo or ezetimibe 10 mg once daily for 2 weeks; or atorvastatin 80 mg along with 800 mg of GSK129226 or placebo once daily for 2 weeks; or monotherapy (100 mg, 300 mg or 800 mg of GSK1292263 or placebo) once daily for 2 weeks.
FG0006 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG0006 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Part B Washout
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG001281 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG0000 subjects
FG001136 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG0000 subjects
FG001145 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG003
Part B Run-in
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG00289 subjects
FG0030 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG00283 subjects
FG0030 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0026 subjects
FG0030 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
Part B Pooled Treatment Arm
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003130 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003127 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
One participant was withdrawn prior to washout period. 34 participants did not complete washout phase. 111 participants did not qualify to continue in the study after completing the Washout Phase. 6 participants were withdrawn during run-in phase and 3 participants were withdrawn during treatment phase.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A
Four participants on 80 mg atorvastatin [either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg], received GSK1292263 800 mg for 2 weeks, and 2 participants not on lipid-modifying treatment received GSK1282263 800 mg alone for 2 weeks.
BG001
Part B
Part B included Washout phase (Participants were washed off their prior lipid-lowering therapy for 4 weeks), Run-in phase (Eligible participants were randomized to receive 10 mg open-labeled atorvastatin or 80 mg open-labeled atorvastatin for a 4-week stabilization run-in period) and Treatment phase (Randomized participants after washout received monotherpy (100 mg, 300 mg or 800 mg of GSK1292263 or placebo) for 2 weeks. Participants in the 10mg atorvastatin run-in group received GSK1292263, 300 mg QD GSK1292263, 800 mg QD GSK1292263, placebo for GSK1292263 or 10 mg open-label ezetimibe for 2 weeks. Participants in the 80 mg atorvastatin run-in group received 800 mg QD GSK1292263 and placebo for GSK1292263 for 2 weeks)
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG001281
BG002287
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Data is presented for Part A
N=6
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG0006
ParticipantsBG0010
ParticipantsBG0026
Title
Measurements
Age, Continuous
Data is presented for Part B
N=281
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG001281
ParticipantsBG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0006
ParticipantsBG001281
ParticipantsBG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
African American/African Heritage
ParticipantsBG0006
ParticipantsBG001281
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Safety Population consisted of all participants who received at least one dose of study medication.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
80 mg Atorvastatin + 800 mg GSK1292263
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
800 mg GSK1292263
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
OG0004
OG0012
Title
Denominators
Categories
Any AE
Title
Measurements
OG0000
OG0012
Any SAE
Title
Measurements
OG000
Primary
Number of Participants With Any AEs and SAEs- Part B (Washout)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
All subject Population consisted of all participants who received at least one dose of study medication.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Pre-treatment
This was the time period prior to Day 1 of Washout Phase.
OG001
Washout
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
Primary
Number of Participants With Any AEs and SAEs- Part B (Run-in)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
All subject Population
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Atorvastatin 10 mg
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
OG001
Atorvastatin 80 mg
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
Primary
Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
All subject Population
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Primary
Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A
Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.
Safety Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)
ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.
All subject Population. Only those participants available at the specified time points were analyzed.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Washout
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)
ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.
All subjects Population. Only those participants present during Run in/Day 28 were evaluated/included.
Posted
Count of Participants
Participants
Day 28
ID
Title
Description
OG000
Atorvastatin 10 mg
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
OG001
Atorvastatin 80 mg
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)
Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
OG003
Primary
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A
Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Safety Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Primary
Number of Participants With Vital Signs of PCI- Part B (Washout)
Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to day 28
ID
Title
Description
OG000
Washout
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
Units
Counts
Participants
OG000
Primary
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)
Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to day 28
ID
Title
Description
OG000
Atorvastatin 10 mg
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
OG001
Atorvastatin 80 mg
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
Units
Counts
Participants
OG000
Primary
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)
Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part A
Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.
Safety Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)
Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells [WBC], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Washout
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)
Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Days 14 and 28
ID
Title
Description
OG000
Atorvastatin 10 mg
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
OG001
Atorvastatin 80 mg
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)
Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A
Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.
Safety Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)
Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase [ALT], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate [CO2/HCO3] and Aspartate aminotransferase [AST]) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Washout
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)
Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Days 14 and 28
ID
Title
Description
OG000
Atorvastatin 10 mg
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
OG001
Atorvastatin 80 mg
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
Units
Counts
Participants
OG000
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)
Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.
All subjects Population.
Posted
Count of Participants
Participants
Up to Day 26
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
Primary
Maximum Observed Concentration (Cmax) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Pharmacokinetic (PK) Parameter Population was defined as participants in the 'PK Concentration' population for whom PK parameters were derived. The 'PK Concentration Population' was defined as participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Primary
Cmax of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
Primary
Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Median
Full Range
hours
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).
PK parameter Population
Posted
Median
Full Range
hours
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Median
Full Range
hours
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Primary
Tlag of GSK1292263- Part B (Pooled Treatment Arm)
Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
PK parameter Population. Only those participants with data available at the indicated time points were analyzed.
Posted
Median
Full Range
hours
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
OG003
Atorvastatin 80 mg + GSK1292263 800 mg
Primary
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
OG001
GSK1292263 800 mg
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Primary
AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
Primary
Trough Concentration of GSK1292263
Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).
PK concentration Population. Data was not collected for this outcome measure.
Posted
On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
OG003
Primary
Cmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
PK parameter Population.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Cmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Primary
Tmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
PK parameter Population.
Posted
Median
Full Range
hours
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
Tmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at specified time points were analyzed.
Posted
Median
Full Range
hours
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Primary
AUC (0-24) of Atorvastatin- Part A
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Primary
AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Primary
Trough Concentration of Atorvastatin
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).
PK parameter Population. Data was not collected for this outcome measure.
Posted
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Primary
Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
All subjects Population. Only those participants available at the specified time points were analyzed.
Posted
Mean
Standard Deviation
Percent change
Baseline and Day 14
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Primary
Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
All subjects Population. Only those participants with data available at the indicated time points were analyzed.
Posted
Mean
Standard Deviation
Perecent change
Baseline and Day 14
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Primary
Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
All subjects Population. Only those participants available at the specified time points were analyzed.
Posted
Mean
Standard Deviation
Percent change
Baseline and Day 14
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
Primary
Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
All subjects Population. Only those participants with data available at the indicated time points were analyzed.
Posted
Mean
Standard Deviation
Percent change
Baseline and Day 14
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Primary
Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
All subjects Population. Only those participants with data available at the indicated time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
millimoles per liter
Baseline and Day 14
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Secondary
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
PK parameter Population.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Secondary
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
Secondary
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
PK parameter Population.
Posted
Median
Full Range
hours
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Secondary
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Median
Full Range
hours
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Secondary
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
PK parameter Population.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
ID
Title
Description
OG000
Atorvastatin 80 mg + GSK1292263 800 mg
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
Units
Counts
Participants
Secondary
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
PK parameter Population. Only those participants available at the specified time points were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms hour per milliliter
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
Secondary
Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected.
Posted
On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
ID
Title
Description
OG000
Atorvastatin 10 mg + GSK1292263 100 mg
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
OG001
Atorvastatin 10 mg + GSK1292263 300 mg
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
OG002
Atorvastatin 10 mg + GSK1292263 800 mg
Time Frame
All AEs and SAEs were collected up to follow-up visit. For Part A- up to Day 26, for Part B (washout)- up to Day 28, for Part B (run-in)- up to day up to day 28 and Part B (treatment)- up to Day 26
Description
All AEs and SAEs for Part A were collected using Safety Population and for Part B using All Subjects Population.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
80 mg Atorvastatin + 800 mg GSK1292263 (Part A)
Participants on 80 mg atorvastatin (either for >=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg) received 800 mg of GSK1292263 for 2 weeks once daily immediately after eating the breakfast meal.
0
4
0
4
0
4
EG001
800 mg GSK1292263 (Part A)
Participants not on lipid-modifying treatment received GSK1282263 alone for 2 weeks once daily immediately after eating the breakfast meal.
0
2
0
2
2
2
EG002
Pre-treatment (Part B)
This was the time period prior to Day 1 of Washout Phase.
0
281
0
281
14
281
EG003
Washout (Part B)
During the 4 weeks washout period, participants were asked to stop their lipid-modifying drugs.
0
281
0
281
37
281
EG004
Atorvastatin 10 mg (Part B Run-in)
After washout participants received atorvastatin 10 mg for a 4-week stabilization Run-in Period.
0
62
0
62
19
62
EG005
Atorvastatin 80 mg (Part B Run-in)
After washout participants received atorvastatin 80 mg for a 4-week stabilization Run-in Period.
0
27
0
27
8
27
EG006
Atorvastatin 10 mg + GSK1292263 100 mg (Part B Treatment)
Participants received 10 mg atorvastatin along with GSK1292263 100 mg once daily for 2 weeks.
0
11
0
11
6
11
EG007
Atorvastatin 10 mg + GSK1292263 300 mg (Part B Treatment)
Participants received 10 mg atorvastatin along with GSK1292263 300 mg once daily for 2 weeks.
0
11
0
11
2
11
EG008
Atorvastatin 10 mg + GSK1292263 800 mg (Part B Treatment)
Participants received 10 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
0
11
0
11
3
11
EG009
Atorvastatin 10 mg + Placebo (Part B Treatment)
Participants received 10 mg atorvastatin along with placebo matching to GSK1292263 once daily for 2 weeks.
0
12
0
12
3
12
EG010
Atorvastatin 10 mg + Ezetimibe 10 mg (Part B Treatment)
Participants received 10 mg atorvastatin along with Ezetimibe 10 mg once daily for 2 weeks.
0
13
0
13
4
13
EG011
Atorvastatin 80 mg + GSK1292263 800 mg (Part B Treatment)
Participants received 80 mg atorvastatin along with GSK1292263 800 mg once daily for 2 weeks.
0
12
0
12
6
12
EG012
Atorvastatin 80 mg + Placebo (Part B Treatment)
Participants received 80 mg atorvastatin along with placebo matching to GSK1292263 once daily for 2 weeks.
0
13
0
13
4
13
EG013
GSK1292263 100 mg (Part B Treatment)
After washout, participants were randomized to receive monotherapy of GSK1292263 100 mg once daily for 2 weeks.
0
11
0
11
5
11
EG014
GSK1292263 300 mg (Part B Treatment)
After washout, participants were randomized to receive monotherapy of GSK1292263 300 mg once daily for 2 weeks.
0
12
0
12
7
12
EG015
GSK1292263 800 mg (Part B Treatment)
After washout, participants were randomized to receive monotherapy of GSK1292263 800 mg once daily for 2 weeks.
0
13
0
13
8
13
EG016
Placebo (Part B Treatment)
After washout, participants were randomized to receive placebo matching to GSK1292263 once daily for 2 weeks.
0
11
0
11
4
11
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected2 at risk
EG0020 affected281 at risk
EG0031 affected281 at risk
EG0040 affected62 at risk
EG0050 affected27 at risk
EG0060 affected11 at risk
EG0071 affected11 at risk
EG0080 affected11 at risk
EG0090 affected12 at risk
EG0100 affected13 at risk
EG0110 affected12 at risk
EG0120 affected13 at risk
EG0130 affected11 at risk
EG0141 affected12 at risk
EG0150 affected13 at risk
EG0161 affected11 at risk
Vomiting
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected2 at risk
EG0020 affected281 at risk
EG003
Phlebitis
Vascular disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected2 at risk
EG0020 affected281 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0025 affected281 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0022 affected281 at risk
EG003
Breast abscess
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Helicobacter infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Influenza
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Injection site infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Headache
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Migraine
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Excoriation
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Musculoskeletal discomfort
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Asthenia
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Oedema peripheral
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Blood pressure increased
Investigations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Cardiac murmur
Investigations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Middle ear effusion
Ear and labyrinth disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0021 affected281 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Tongue ulceration
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Viral infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Pyrexia
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hot flush
Vascular disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hypersomnia
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
VIIth nerve paralysis
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Fatigue
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Upper-airway cough syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hordeolum
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Flushing
Vascular disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Blood calcium decreased
Investigations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Personality change
Psychiatric disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Hypoacusis
Ear and labyrinth disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected2 at risk
EG0020 affected281 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.