Infection, Human Immunodeficiency Virus
Conditions
Keywords
IDX12899, adaptive, monotherapy, pharmacokinetics, Treatment-naive, HIV-1, GSK2248761, NNRTI, HIV Infections, treatment naive
Brief summary
GSK has in-licensed a novel NNRTI-class candidate (GSK2248761, IDX12899) for the treatment of subjects with HIV-1 infection from Idenix Pharmaceuticals. Idenix Pharmaceuticals completed a proof-of-concept study evaluating GSK2248761 monotherapy over seven days in forty treatment-naïve subjects infected with HIV-1. GSK2248761 doses sequentially evaluated were 800 mg QD, 400 mg QD, 200 mg QD and 100mg QD. This study will evaluate a lower dose, or doses, of GSK2248761 to better characterize the dose-response and concentration-response curves. The results from this study will be used to select doses for future clinical studies in HIV-1 infected subjects.
Interventions
DRUGGSK2248761
GSK2248761 30 mg capsule once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.
DRUGLopinavir/ritonavir
Lopinavir 400 mg and ritonovir 100 mg every 12 hours for 28 days. Lopinavir/ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class. Kaletra is a trademark of Abbott Laboratories.
DRUGHAART
Highly Active Antiretroviral therapy of the doctor's choice.
DRUGPlacebo
Placebo is a capsule with no drug in it.
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female, 21 to 65 years of age. * Female of non-childbearing potential defined as: being post-menopausal, defined as 12 months of spontaneous amenorrhea and having a serum FSH level \>40 MIU/ml at Screening OR have had a documented bilateral tubal ligation or hysterectomy of at least 6 months prior to study initiation, bilateral oophorectomy or bilateral tubal ligation. * Plasma HIV-1 RNA value \>= 5000 copies/mL. * CD4+ count \>= 200 cells/mm3. * Is antiretroviral treatment-naïve and agrees not to start antiretroviral therapy prior to clinic check-in (Day-1). * Subject agrees to start a standard HAART regimen on Day 8 of the study or Kaletra monotherapy for 28 days within 24 hours after the last dose of study medication. * Capable of giving written informed consent, which includes being willing and able to comply with the requirements and restrictions listed in the consent form.
Exclusion criteria
* Subject is pregnant as determined by a positive urine/serum pregnancy test at Screening and Day -1. * Lactating females. * Male subjects of reproductive potential and unwilling to use double barrier method of contraception (e.g., condom plus spermicide) and continue to use an adequate method of birth control for at least 30 days after the last dose of the study drug. * Has a positive screening Hepatitis B surface antigen, positive screening Hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the Hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study. * History of regular alcohol consumption within 6 months of Screening as defined as: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (\ 240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits * Has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine and PCP. * History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the Principal Investigator, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled. Note: Study drugs include GSK2248761 placebo or the follow-up HAART or Kaletra therapy. * Received an immunomodulating agent (e.g., interleukin-2) or immunotherapeutic vaccine within 30 days before Day -1. * Requires a medication that is a known substrate, inhibitor and/or inducer of CYP3A4. * Has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dosing day. * Has ever had an AIDS-defining illness. * Has a history of or has a currently active clinically important disease other than HIV-1 infection that, in the opinion of the Investigator, may put the subject at risk because of participation in this study (including renal and hepatic impairment, active infections including tuberculosis or opportunistic infection, malignancy and cardiac dysfunction). * Has an intestinal malabsorption (e.g., structural defects, digestive failure, enzyme deficiencies, etc). * Has a pre-existing NNRTI drug resistance based on genotyping at Screening. * Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56 day period. * Subject has any of the following laboratory parameters at Screening (a single repeat is allowed for eligibility determination): Hemoglobin \<8.5 g/dL, Neutrophil count \<1000 cells/mm3, Platelet count \<100,000 cells/mm3, Serum creatinine \> the upper limit of normal (ULN), AST or ALT \<= 2.5 x ULN. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | Baseline (Screening), Day 1 and Day 8 | Whole venous blood samples were obtained from each participant for the analysis of lymphocyte subsets by flow cytometry (total lymphocyte counts, percentage, CD4+ cell counts, and CD8+ cell counts) at Screening, Day 1 and Day 8. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values (Day 1 and Day 8). Baseline was defined as Screening. |
| GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax | Day 7 (Pre -dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) | The C0 was defined as the concentration of drug in plasma, before dose administration on Day 7. Cτ, was defined as the concentration of drug in the plasma at the end of dosing interval. The Cmin was defined as the minimum concentration of the drug in plasma during one dosing interval on Day 7. Cmax represents the maximum concentration of GSK2248761 in the plasma on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis. |
| GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag) | Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose) | Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 1. The t1/2 was defined as the time measured for plasma concentration to decrease by one half. The tlag was defined as the time taken for the drug GSK2248761, to appear in the systemic circulation following administration. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis. |
| GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F) | Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) | The Clearance factor was defined as the volume of plasma cleared of the drug GSK2248761, per unit time. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis. |
| GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ) | Day 7 (Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose) | AUC(0-τ) is the AUC to the end of dosing period. For Day 7, it is the AUC measured at the end of the dosing period at Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis. |
| GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax | Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose) | Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis |
| GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2 | Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose) | The t1/2 was defined as the time measured for plasma concentration to decrease by one half. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis |
| Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Up to 38 days | 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. |
| Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameters for Basophils, eosinophils, lymphocytes, monocytes, and white blood cell count from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Hemoglobin | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter hemoglobin from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Platelet Count | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter platelet count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter red blood cell count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Parameters- Total Neutrophil | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter total neutrophil count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter MCH, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The change from baseline data for hematology parameter MCV, was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters- Hematocrit | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter Hematocrit, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for hematology parameter Mean Corpuscle Hemoglobin concentration, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters Albumin and total protein, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters- Blood urea nitrogen, triglycerides, glucose, creatinine, calcium, cholesterol, total bilirubin, and direct bilirubin. The change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry paramaters- alkaline phosphatase, alanine amino transferase, aspartate amino transferase, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters- sodium, potassium and carbon dioxide or bicarbonate, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry paramaters- phosphorous, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters Uric acid, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters Thyroxine, free the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14) | The data for clinical chemistry parameters Thyroxine total, thyroxine binding globulin, Total T3 the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, Day 4, Day 7, Day 8 and follow-up | Triplicate 12-lead ECGs were collected at different timepoints, after participants were supine for 5 minutes, during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. The three consecutive determinations were collected 5 plus or minus 2 minutes apart and all three tracings were recorded. The participants with abnormal values categorized as abnormal clinically significant (CS) and not clinically significant (NCS) were reported. |
| Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline (pre-dose at Day -1 or Day 1) and Day 1, 4, 7 , Day 8 and Follow-up (Day 14) | Vital sign measurements for SBP and DBP after sitting for 5 minutes were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline in HR | Baseline (pre-dose at Day -1 or Day 1) and Day 1 (4-hour), Day 4 (Pre-dose and 4 hour), Day 7 (pre-dose and 4-hour), Day 8 and follow up (Day 14) | Vital sign measurements for HR after sitting for 5 minutes were measured. The average mean values were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline Through Day 8 in Plasma HIV-1 RNA | Baseline (pre-dose Day 1) to Day 8 | The quantitative analysis of plasma was done to evaluate the amount of HIV-1 RNA at Day 1,2,3,4,5,6,7, 8 and End of treatment visit. The quantification was done using a Polymerase chain reactor (PCR). The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| Change From Baseline to Nadir in Plasma HIV-1 RNA | Baseline (pre-dose Day 1) to Day 8 | The quantification of plasma HIV-1 RNA, was conducted for the change from baseline to on treatment nadir (maximum change) before starting HAART or Kaletra monotherapy on Day 8. The quantification was done using a PCR. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise. |
| HIV-1 Rate of Decline by Treatment | Day 1 to Day 8 | The rate of decrease in the viral load of HIV-1 virus in response to individual treatment was measured. The viral load data was assumed to have a log normal prior distribution and followed linear decline with non-informative conjugate prior densities. The rate of decline (slope of the day) for each treatment was measured using a PCR from Day 1 to Day 8. The slope has been reported as mean. |
| GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24]) | Day 1 (Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) | AUC (0-24), measured the plasma concentration of GSK2248761 against time, from time zero (pre-dose) to 24 hrs post-dose AUC (0-24) and from time zero to extrapolated infinite time AUC (0-∞). Serial blood samples were collected on Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis. |
| GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) | Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours) | Cmax represents the maximum concentration of GSK2248761 in the plasma. C24 is defined as the measure of plasma drug concentration of GSK2248761, 24 hours post dose, determined on Day 1. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.Data for dose normalized Cmax and C24 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration | (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) on Day 1 and Day 7 | The accumulation ratio is based on the parameters, Cmax, AUC(0-tau), AUC(0-24), C(tau), C24, AND AUC(0-inf). The accumulation ratio Ro was the ratio of AUC(0-tau) on Day 7 to that of AUC(0-24) on Day 1; the accumulation ratio R (Cmax) was the ratio of Cmax on Day 7 to that of Cmax on Day 1; the accumulation ratio R(Ctau) was the ratio of Ctau on Day 7 to the ratio of C24 on Day 1 and the Time Invariance Ratio Rs was defined as the ratio of AUC(0-tau) on Day 7 to that of AUC(0-inf) on Day 1. The ratio has been reported as number. |
| Change From Baseline in Reverse Transcriptase Sequences of HIV-1 at Day 8 | Baseline (Screening) and Day 8 | None of the participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations at codons 90, 98, 100, 101, 103, 106, 108, 138, 179, 181, 188, 190, 225, or 230 at either Day 1 or Day 8. No mutation selected by GSK2248761 in vitro was observed for any participant at either Day 1 or Day 8. This data for Change from baseline in reverse transcriptase sequences of HIV-1 at Day 8 not collected. |
| Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7 | Day 7 (Pre - dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) and Days 2, 3, 4. 5 and 6: pre-dose only | The pre-dose GSK2248761 steady state concentration, following repeated dose administration from Day 2 through Day 7 was assessed. Serial dose sampling was done on each day of Day 2, 3, 4, 5 and Day 6 and for Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose), before the administration of the study drug daily. |
| PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7 | Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. The dose proportionality effects of IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg, following repeat dose administration on Day 7 for the PK parameter AUC(0-tau) has been reported. |
| PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7 | Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. Data for Ctau on Day 1 is presented for concentration at 24 hours post-dose on Day 1. |
| Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | Baseline (Screening), Day 1 and Day 8 | Data for CD4+ and CD8+ cells was collected at Screening, Day 1 and Day 8. The percent change from baseline was reported at Day 1 and Day 8. Baseline was defined as Screening. The percent change from baseline was calculated as post-randomization value minus the baseline value. |
Countries
Argentina
Participant flow
Recruitment details
A total of 8 participants with Treatment-Naive, Human Immuno deficiency virus (HIV-1) infection were randomized to the study. The study was conducted from 20 October 2009 to 28 November 2009 at one center in Argentina.
Pre-assignment details
One participant was initially enrolled in the study, however withdrew consent prior to randomization. The study was planned to be conducted in 2 cohorts, however based on safety and antiviral activity of Cohort 1, a second cohort of participants was not needed and the study was stopped.
Participants by arm
| Arm | Count |
|---|---|
| GSK2248761 30 mg Eligible participants received 3 capsules of GSK2248761 10 mg orally once daily dosed with 360 mL water after a standard breakfast, upto 7-days. Participants were to have fasted 4 hours after dosing. Unless otherwise instructed participants were not to recline (remained upright) for the first 4 hours following oral administration. On Day 8 participants received either Kaletra or HAART for 28 days | 6 |
| Placebo Eligible participants matching placebo capsules to GSK2248761 10 mg capsules orally once daily dosed with 360 mL water after a standard breakfast upto 7-days. Participants were to have fasted 4 hours after dosing. Unless otherwise instructed participants were not to recline (remained upright) for the first 4 hours following oral administration. On Day 8 participants received either Kaletra or HAART for 28 days | 2 |
| Total | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | GSK2248761 30 mg |
|---|---|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 5.66 | 33.3 years STANDARD_DEVIATION 7.15 | 35.0 years STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 4 / 6 | 1 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 |
Outcome results
Primary
Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8.
Whole venous blood samples were obtained from each participant for the analysis of lymphocyte subsets by flow cytometry (total lymphocyte counts, percentage, CD4+ cell counts, and CD8+ cell counts) at Screening, Day 1 and Day 8. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values (Day 1 and Day 8). Baseline was defined as Screening.
Time frame: Baseline (Screening), Day 1 and Day 8
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD4+ cells, Day 1 | 1.2 per cubic millimeter | Standard Deviation 76.32 |
| GSK2248761 30 mg | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD4+ cells, Day 8 | 87.5 per cubic millimeter | Standard Deviation 58.49 |
| GSK2248761 30 mg | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD8+ cells, Day 1 | 123.5 per cubic millimeter | Standard Deviation 348.9 |
| GSK2248761 30 mg | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD8+ cells, Day 8 | 313.3 per cubic millimeter | Standard Deviation 218.85 |
| Placebo | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD8+ cells, Day 8 | 531.5 per cubic millimeter | Standard Deviation 539.52 |
| Placebo | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD4+ cells, Day 1 | 76.0 per cubic millimeter | Standard Deviation 5.66 |
| Placebo | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD8+ cells, Day 1 | 526.0 per cubic millimeter | Standard Deviation 169.71 |
| Placebo | Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. | CD4+ cells, Day 8 | 102.0 per cubic millimeter | Standard Deviation 107.48 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein
The data for clinical chemistry parameters Albumin and total protein, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 2 | -0.17 gram per deciliter | Standard Deviation 0.207 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 4 | -0.08 gram per deciliter | Standard Deviation 0.248 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 7 | -0.10 gram per deciliter | Standard Deviation 0.283 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 8 | -0.05 gram per deciliter | Standard Deviation 0.383 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Follow-up | -0.07 gram per deciliter | Standard Deviation 0.137 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 2 | -0.45 gram per deciliter | Standard Deviation 0.302 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 4 | -0.10 gram per deciliter | Standard Deviation 0.385 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 7 | 0.10 gram per deciliter | Standard Deviation 0.494 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 8 | 0.00 gram per deciliter | Standard Deviation 0.636 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Follow-up | -0.30 gram per deciliter | Standard Deviation 0.268 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 7 | 0.05 gram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 2 | -0.20 gram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 2 | -0.55 gram per deciliter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 4 | 0.00 gram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Follow-up | -0.20 gram per deciliter | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 7 | -0.05 gram per deciliter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 4 | -0.10 gram per deciliter | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Day 8 | -0.10 gram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Total protein, Day 8 | -0.25 gram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein | Albumin, Follow-up | 0.05 gram per deciliter | Standard Deviation 0.071 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase
The data for clinical chemistry paramaters- alkaline phosphatase, alanine amino transferase, aspartate amino transferase, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Follow-up | 4.2 International units (IU) per liter | Standard Deviation 24.96 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 8 | 3.7 International units (IU) per liter | Standard Deviation 24.4 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 4 | -1.5 International units (IU) per liter | Standard Deviation 10.33 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Follow-up | -7.2 International units (IU) per liter | Standard Deviation 21.81 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 2 | -3.0 International units (IU) per liter | Standard Deviation 6.63 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 2 | 0.8 International units (IU) per liter | Standard Deviation 4.17 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 8 | 3.3 International units (IU) per liter | Standard Deviation 14.88 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 4 | -0.2 International units (IU) per liter | Standard Deviation 7.31 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 4 | -2.0 International units (IU) per liter | Standard Deviation 15.02 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 7 | -0.3 International units (IU) per liter | Standard Deviation 7.69 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 7 | 1.8 International units (IU) per liter | Standard Deviation 10.83 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 8 | 1.7 International units (IU) per liter | Standard Deviation 9.4 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 7 | 1.7 International units (IU) per liter | Standard Deviation 21.81 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Follow-up | -0.2 International units (IU) per liter | Standard Deviation 8.4 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 2 | -5.8 International units (IU) per liter | Standard Deviation 7.14 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Follow-up | 2.5 International units (IU) per liter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 2 | -16.0 International units (IU) per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 4 | -16.0 International units (IU) per liter | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 7 | -7.5 International units (IU) per liter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Day 8 | -14.5 International units (IU) per liter | Standard Deviation 6.36 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alkaline phosphatase, Follow-up | -9.5 International units (IU) per liter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 2 | 0.5 International units (IU) per liter | Standard Deviation 6.36 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 4 | -3.5 International units (IU) per liter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 7 | -3.5 International units (IU) per liter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Day 8 | 0.0 International units (IU) per liter | Standard Deviation 5.66 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Alanine amino transferase, Follow-up | -1.5 International units (IU) per liter | Standard Deviation 6.36 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 2 | 1.0 International units (IU) per liter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 4 | -4.5 International units (IU) per liter | Standard Deviation 3.54 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 7 | -3.0 International units (IU) per liter | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase | Aspartate amino transferase, Day 8 | 0.0 International units (IU) per liter | Standard Deviation 5.66 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Phosphorus
The data for clinical chemistry paramaters- phosphorous, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 4 | 0.07 millimole per liter | Standard Deviation 0.799 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 8 | -0.27 millimole per liter | Standard Deviation 0.662 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 7 | -0.17 millimole per liter | Standard Deviation 0.628 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Follow-up | -0.58 millimole per liter | Standard Deviation 0.634 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 2 | -0.05 millimole per liter | Standard Deviation 0.524 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Follow-up | -0.95 millimole per liter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 2 | -0.80 millimole per liter | Standard Deviation 0.707 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 4 | 0.25 millimole per liter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 7 | -0.00 millimole per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Phosphorus | Phosphorus, Day 8 | -0.35 millimole per liter | Standard Deviation 0.071 |
Primary
Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate
The data for clinical chemistry parameters- sodium, potassium and carbon dioxide or bicarbonate, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Follow-up | 2.3 milliequivalents per liter | Standard Deviation 1.63 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 8 | -0.18 milliequivalents per liter | Standard Deviation 0.371 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 4 | -0.8 milliequivalents per liter | Standard Deviation 1.6 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Follow-up | -0.08 milliequivalents per liter | Standard Deviation 0.36 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 2 | -0.02 milliequivalents per liter | Standard Deviation 0.293 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 2 | -0.80 milliequivalents per liter | Standard Deviation 2.384 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 8 | -1.7 milliequivalents per liter | Standard Deviation 1.51 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 4 | 3.17 milliequivalents per liter | Standard Deviation 1.488 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 4 | 0.10 milliequivalents per liter | Standard Deviation 0.434 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 7 | 2.93 milliequivalents per liter | Standard Deviation 1.85 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 7 | -1.5 milliequivalents per liter | Standard Deviation 1.64 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 8 | 0.87 milliequivalents per liter | Standard Deviation 2.471 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 7 | -0.17 milliequivalents per liter | Standard Deviation 0.314 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Follow-up | 2.03 milliequivalents per liter | Standard Deviation 2.187 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 2 | -1.2 milliequivalents per liter | Standard Deviation 1.17 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Follow-up | -0.30 milliequivalents per liter | Standard Deviation 1.131 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 2 | -0.5 milliequivalents per liter | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 4 | 1.0 milliequivalents per liter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 7 | 0.0 milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Day 8 | -0.5 milliequivalents per liter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Sodium, Follow-up | 1.0 milliequivalents per liter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 2 | -0.25 milliequivalents per liter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 4 | 0.10 milliequivalents per liter | Standard Deviation 0.566 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 7 | -0.10 milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Day 8 | -0.00 milliequivalents per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Potassium, Follow-up | -0.30 milliequivalents per liter | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 2 | -1.35 milliequivalents per liter | Standard Deviation 2.051 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 4 | 2.70 milliequivalents per liter | Standard Deviation 4.101 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 7 | 3.60 milliequivalents per liter | Standard Deviation 2.121 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate | Carbondioxide, Day 8 | 1.65 milliequivalents per liter | Standard Deviation 1.768 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free
The data for clinical chemistry parameters Thyroxine, free the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 4 | 0.108 Picomole per liter | Standard Deviation 0.132 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 8 | 0.117 Picomole per liter | Standard Deviation 0.1221 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 7 | 0.065 Picomole per liter | Standard Deviation 0.1011 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Follow- up | 0.072 Picomole per liter | Standard Deviation 0.1332 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 2 | -0.018 Picomole per liter | Standard Deviation 0.0768 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Follow- up | 0.135 Picomole per liter | Standard Deviation 0.1485 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 2 | 0.015 Picomole per liter | Standard Deviation 0.0636 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 4 | 0.190 Picomole per liter | Standard Deviation 0.0283 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 7 | 0.120 Picomole per liter | Standard Deviation 0.1414 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free | Thyroxine free, Day 8 | 0.130 Picomole per liter | Standard Deviation 0.0424 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3.
The data for clinical chemistry parameters Thyroxine total, thyroxine binding globulin, Total T3 the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Follow-up | -0.005 Nanomoles per liter | Standard Deviation 0.1945 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 2 | -0.60 Nanomoles per liter | Standard Deviation 0.648 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 4 | -0.08 Nanomoles per liter | Standard Deviation 0.979 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 7 | -0.28 Nanomoles per liter | Standard Deviation 0.773 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 8 | 0.00 Nanomoles per liter | Standard Deviation 0.874 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Follow-up | -0.37 Nanomoles per liter | Standard Deviation 1.019 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 2 | -0.33 Nanomoles per liter | Standard Deviation 5.645 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 4 | -5.00 Nanomoles per liter | Standard Deviation 3.688 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 7 | -0.67 Nanomoles per liter | Standard Deviation 7.005 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 8 | 0.17 Nanomoles per liter | Standard Deviation 1.169 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Follow-up | -1.83 Nanomoles per liter | Standard Deviation 2.787 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 2 | -0.013 Nanomoles per liter | Standard Deviation 0.1334 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 4 | 0.068 Nanomoles per liter | Standard Deviation 0.218 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 7 | -0.055 Nanomoles per liter | Standard Deviation 0.1435 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 8 | -0.035 Nanomoles per liter | Standard Deviation 0.1252 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Follow-up | 0.375 Nanomoles per liter | Standard Deviation 0.1344 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 7 | -3.00 Nanomoles per liter | Standard Deviation 8.485 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 2 | -0.40 Nanomoles per liter | Standard Deviation 0.707 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 4 | 0.310 Nanomoles per liter | Standard Deviation 0.2687 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 4 | 0.50 Nanomoles per liter | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 8 | -1.00 Nanomoles per liter | Standard Deviation 2.828 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 7 | 0.10 Nanomoles per liter | Standard Deviation 0.707 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 8 | 0.190 Nanomoles per liter | Standard Deviation 0.0141 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Day 8 | 0.00 Nanomoles per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Follow-up | -1.00 Nanomoles per liter | Standard Deviation 8.485 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine total, Follow-up | 0.05 Nanomoles per liter | Standard Deviation 1.202 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 7 | 0.225 Nanomoles per liter | Standard Deviation 0.2333 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 2 | 2.00 Nanomoles per liter | Standard Deviation 2.828 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Total T3, Day 2 | 0.170 Nanomoles per liter | Standard Deviation 0.2404 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. | Thyroxine binding globulin, Day 4 | -6.50 Nanomoles per liter | Standard Deviation 3.536 |
Primary
Change From Baseline in Clinical Chemistry Paramaters- Uric Acid
The data for clinical chemistry parameters Uric acid, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 4 | 0.17 Micromole per liter | Standard Deviation 0.408 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 8 | -0.60 Micromole per liter | Standard Deviation 0.97 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 7 | -0.15 Micromole per liter | Standard Deviation 0.561 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Follow-up | -0.53 Micromole per liter | Standard Deviation 0.784 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 2 | 0.27 Micromole per liter | Standard Deviation 0.25 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Follow-up | -0.80 Micromole per liter | Standard Deviation 0.566 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 2 | -0.55 Micromole per liter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 4 | -0.70 Micromole per liter | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 7 | -0.80 Micromole per liter | Standard Deviation 0.707 |
| Placebo | Change From Baseline in Clinical Chemistry Paramaters- Uric Acid | Uric acid, Day 8 | -1.05 Micromole per liter | Standard Deviation 0.071 |
Primary
Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin.
The data for clinical chemistry parameters- Blood urea nitrogen, triglycerides, glucose, creatinine, calcium, cholesterol, total bilirubin, and direct bilirubin. The change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 4 | -19.8 milligram per deciliter | Standard Deviation 16.47 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 7 | -0.05 milligram per deciliter | Standard Deviation 0.055 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 8 | -0.05 milligram per deciliter | Standard Deviation 0.055 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Follow-up | 0.02 milligram per deciliter | Standard Deviation 0.075 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 2 | 1.5 milligram per deciliter | Standard Deviation 7.2 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 4 | 4.3 milligram per deciliter | Standard Deviation 5.32 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 7 | 1.0 milligram per deciliter | Standard Deviation 7.67 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 8 | 2.7 milligram per deciliter | Standard Deviation 6.38 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Follow-up | -2.2 milligram per deciliter | Standard Deviation 7.41 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 2 | -17.8 milligram per deciliter | Standard Deviation 19.05 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 4 | -0.08 milligram per deciliter | Standard Deviation 0.041 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 7 | 5.2 milligram per deciliter | Standard Deviation 21.44 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 8 | 20.8 milligram per deciliter | Standard Deviation 63.05 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Follow-up | -3.0 milligram per deciliter | Standard Deviation 12.63 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 2 | 1.3 milligram per deciliter | Standard Deviation 9.18 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 4 | 0.0 milligram per deciliter | Standard Deviation 10.92 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 7 | -1.8 milligram per deciliter | Standard Deviation 7.86 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 8 | -5.2 milligram per deciliter | Standard Deviation 10.72 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Follow-up | 3.0 milligram per deciliter | Standard Deviation 5.76 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 2 | -0.048 milligram per deciliter | Standard Deviation 0.077 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 4 | 0.025 milligram per deciliter | Standard Deviation 0.0586 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 7 | -0.003 milligram per deciliter | Standard Deviation 0.0455 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 8 | -0.060 milligram per deciliter | Standard Deviation 0.0569 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Follow-up | -0.003 milligram per deciliter | Standard Deviation 0.1183 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 2 | -0.25 milligram per deciliter | Standard Deviation 0.176 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 4 | -0.13 milligram per deciliter | Standard Deviation 0.301 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 7 | -0.40 milligram per deciliter | Standard Deviation 0.322 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 8 | -0.47 milligram per deciliter | Standard Deviation 0.418 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Follow-up | 0.08 milligram per deciliter | Standard Deviation 0.299 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 2 | -11.8 milligram per deciliter | Standard Deviation 13.92 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 4 | -15.3 milligram per deciliter | Standard Deviation 28.72 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 7 | -12.0 milligram per deciliter | Standard Deviation 35.25 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 8 | -8.3 milligram per deciliter | Standard Deviation 41.15 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Follow-up | -5.5 milligram per deciliter | Standard Deviation 33.44 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 2 | -0.12 milligram per deciliter | Standard Deviation 0.16 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 4 | -0.08 milligram per deciliter | Standard Deviation 0.133 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 7 | -0.03 milligram per deciliter | Standard Deviation 0.121 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 8 | -0.08 milligram per deciliter | Standard Deviation 0.075 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Follow-up | 0.08 milligram per deciliter | Standard Deviation 0.24 |
| GSK2248761 30 mg | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 2 | -0.08 milligram per deciliter | Standard Deviation 0.041 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 8 | -0.10 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 4 | 0.00 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 4 | 0.025 milligram per deciliter | Standard Deviation 0.0071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 7 | 0.05 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 4 | -17.5 milligram per deciliter | Standard Deviation 10.61 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 8 | 0.00 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 7 | 0.035 milligram per deciliter | Standard Deviation 0.0919 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Follow-up | 0.10 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 4 | -0.15 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 2 | -1.0 milligram per deciliter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 8 | -0.040 milligram per deciliter | Standard Deviation 0.1273 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 4 | 4.0 milligram per deciliter | Standard Deviation 5.66 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 7 | -20.5 milligram per deciliter | Standard Deviation 7.78 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 7 | 3.5 milligram per deciliter | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Follow-up | 0.060 milligram per deciliter | Standard Deviation 0.1273 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Day 8 | 5.5 milligram per deciliter | Standard Deviation 9.19 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Direct bilirubin, Day 2 | 0.00 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Blood urea nitrogen, Follow-up | 1.0 milligram per deciliter | Standard Deviation 15.56 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 2 | -0.25 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 2 | 5.0 milligram per deciliter | Standard Deviation 14.14 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 8 | -13.5 milligram per deciliter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 4 | 5.5 milligram per deciliter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 4 | 0.05 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 7 | 20.5 milligram per deciliter | Standard Deviation 27.58 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 7 | -0.05 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Day 8 | 34.0 milligram per deciliter | Standard Deviation 21.21 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 7 | -0.20 milligram per deciliter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Triglycerides, Follow-up | 114.0 milligram per deciliter | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Follow-up | -0.5 milligram per deciliter | Standard Deviation 17.68 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 2 | 6.0 milligram per deciliter | Standard Deviation 4.24 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Day 8 | -0.45 milligram per deciliter | Standard Deviation 0.354 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 4 | -0.5 milligram per deciliter | Standard Deviation 12.02 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Follow-up | 0.00 milligram per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 7 | -1.0 milligram per deciliter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Calcium, Follow-up | 0.05 milligram per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Day 8 | -5.0 milligram per deciliter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Total bilirubin, Day 2 | -0.10 milligram per deciliter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Glucose, Follow-up | 10.0 milligram per deciliter | Standard Deviation 4.24 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Cholesterol, Day 2 | -12.0 milligram per deciliter | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. | Creatinine, Day 2 | 0.000 milligram per deciliter | Standard Deviation 0 |
Primary
Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count
The data for hematology parameters for Basophils, eosinophils, lymphocytes, monocytes, and white blood cell count from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 7 | 1.7 thousand cells per microliter | Standard Deviation 7.53 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 8 | 273.3 thousand cells per microliter | Standard Deviation 357.64 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 7 | -38.3 thousand cells per microliter | Standard Deviation 106.85 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Follow-Up | -110.0 thousand cells per microliter | Standard Deviation 375.34 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Follow-Up | -3.3 thousand cells per microliter | Standard Deviation 10.33 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 2 | 28.3 thousand cells per microliter | Standard Deviation 71.11 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 8 | -96.7 thousand cells per microliter | Standard Deviation 229.49 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 4 | 33.3 thousand cells per microliter | Standard Deviation 76.59 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 4 | 8.3 thousand cells per microliter | Standard Deviation 9.83 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 7 | -15.0 thousand cells per microliter | Standard Deviation 135.17 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Follow-Up | -63.3 thousand cells per microliter | Standard Deviation 153.84 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 8 | 23.3 thousand cells per microliter | Standard Deviation 103.67 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 2 | -1.7 thousand cells per microliter | Standard Deviation 35.45 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Follow-Up | 10.0 thousand cells per microliter | Standard Deviation 143.67 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 2 | -120.0 thousand cells per microliter | Standard Deviation 272.18 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 2 | 148.3 thousand cells per microliter | Standard Deviation 649.78 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 8 | 3.3 thousand cells per microliter | Standard Deviation 8.16 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 4 | 758.3 thousand cells per microliter | Standard Deviation 896.78 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 4 | 268.3 thousand cells per microliter | Standard Deviation 298.83 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 7 | 45.0 thousand cells per microliter | Standard Deviation 1017.7 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 4 | -60.0 thousand cells per microliter | Standard Deviation 150.33 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 8 | 500.0 thousand cells per microliter | Standard Deviation 776.79 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 7 | 126.7 thousand cells per microliter | Standard Deviation 415.44 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Follow-Up | -90.0 thousand cells per microliter | Standard Deviation 699.29 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 2 | -1.7 thousand cells per microliter | Standard Deviation 4.08 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Follow-Up | -110.0 thousand cells per microliter | Standard Deviation 2573.87 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 2 | -5.0 thousand cells per microliter | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 4 | 5.0 thousand cells per microliter | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 7 | -10.0 thousand cells per microliter | Standard Deviation 14.14 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Day 8 | -10.0 thousand cells per microliter | Standard Deviation 14.14 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Basophils, Follow-Up | -15.0 thousand cells per microliter | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 2 | -120.0 thousand cells per microliter | Standard Deviation 141.42 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 4 | -20.0 thousand cells per microliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 7 | -50.0 thousand cells per microliter | Standard Deviation 28.28 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Day 8 | -80.0 thousand cells per microliter | Standard Deviation 70.71 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Eosinophils, Follow-Up | -135.0 thousand cells per microliter | Standard Deviation 162.63 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 2 | 315.0 thousand cells per microliter | Standard Deviation 1067.73 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 4 | 260.0 thousand cells per microliter | Standard Deviation 296.98 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 7 | 180.0 thousand cells per microliter | Standard Deviation 410.12 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Day 8 | 480.0 thousand cells per microliter | Standard Deviation 1060.66 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Lymphocytes, Follow-Up | 50.0 thousand cells per microliter | Standard Deviation 551.54 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 2 | 125.0 thousand cells per microliter | Standard Deviation 176.78 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 4 | 120.0 thousand cells per microliter | Standard Deviation 155.56 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 7 | 25.0 thousand cells per microliter | Standard Deviation 77.78 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Day 8 | 75.0 thousand cells per microliter | Standard Deviation 134.35 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | Monocytes, Follow-Up | -115.0 thousand cells per microliter | Standard Deviation 35.36 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 2 | 1295.0 thousand cells per microliter | Standard Deviation 2849.64 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 4 | -10.0 thousand cells per microliter | Standard Deviation 155.56 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 7 | -600.0 thousand cells per microliter | Standard Deviation 367.7 |
| Placebo | Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count | White blood cell, Day 8 | -240.0 thousand cells per microliter | Standard Deviation 1513.21 |
Primary
Change From Baseline in Hematology Paramaters- Hematocrit
The data for hematology parameter Hematocrit, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hematocrit | Day 4 | -0.92 percentage of red blood cells | Standard Deviation 2.11 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hematocrit | Day 8 | -1.45 percentage of red blood cells | Standard Deviation 1.508 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hematocrit | Day 7 | -0.80 percentage of red blood cells | Standard Deviation 2.563 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hematocrit | Follow-up | -2.78 percentage of red blood cells | Standard Deviation 1.907 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hematocrit | Day 2 | -1.22 percentage of red blood cells | Standard Deviation 1.286 |
| Placebo | Change From Baseline in Hematology Paramaters- Hematocrit | Follow-up | -3.55 percentage of red blood cells | Standard Deviation 0.919 |
| Placebo | Change From Baseline in Hematology Paramaters- Hematocrit | Day 2 | -2.15 percentage of red blood cells | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Hematology Paramaters- Hematocrit | Day 4 | 1.70 percentage of red blood cells | Standard Deviation 3.536 |
| Placebo | Change From Baseline in Hematology Paramaters- Hematocrit | Day 7 | -1.85 percentage of red blood cells | Standard Deviation 0.495 |
| Placebo | Change From Baseline in Hematology Paramaters- Hematocrit | Day 8 | -1.55 percentage of red blood cells | Standard Deviation 1.202 |
Primary
Change From Baseline in Hematology Paramaters- Hemoglobin
The data for hematology parameter hemoglobin from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 4 | -0.28 gram per decilitre | Standard Deviation 0.794 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 8 | -0.48 gram per decilitre | Standard Deviation 0.585 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 7 | -0.25 gram per decilitre | Standard Deviation 0.864 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hemoglobin | Follow-up | -0.93 gram per decilitre | Standard Deviation 0.55 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 2 | -0.40 gram per decilitre | Standard Deviation 0.316 |
| Placebo | Change From Baseline in Hematology Paramaters- Hemoglobin | Follow-up | -1.00 gram per decilitre | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 2 | -0.50 gram per decilitre | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 4 | 0.60 gram per decilitre | Standard Deviation 1.273 |
| Placebo | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 7 | -0.45 gram per decilitre | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Hematology Paramaters- Hemoglobin | Day 8 | -0.45 gram per decilitre | Standard Deviation 0.354 |
Primary
Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration
The data for hematology parameter Mean Corpuscle Hemoglobin concentration, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 4 | 0.05 percentage of red blood cells | Standard Deviation 0.373 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 8 | 0.02 percentage of red blood cells | Standard Deviation 0.214 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 7 | 0.07 percentage of red blood cells | Standard Deviation 0.361 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Follow-up | -0.03 percentage of red blood cells | Standard Deviation 0.301 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 2 | 0.02 percentage of red blood cells | Standard Deviation 0.445 |
| Placebo | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Follow-up | 0.45 percentage of red blood cells | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 2 | 0.55 percentage of red blood cells | Standard Deviation 0.778 |
| Placebo | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 4 | 0.15 percentage of red blood cells | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 7 | 0.40 percentage of red blood cells | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration | Day 8 | 0.15 percentage of red blood cells | Standard Deviation 0.212 |
Primary
Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH)
The data for hematology parameter MCH, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 4 | 0.08 picogram | Standard Deviation 0.147 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 8 | 0.07 picogram | Standard Deviation 0.151 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 7 | 0.03 picogram | Standard Deviation 0.32 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Follow-up | 0.13 picogram | Standard Deviation 0.367 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 2 | 0.07 picogram | Standard Deviation 0.197 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Follow-up | 0.25 picogram | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 2 | 0.45 picogram | Standard Deviation 0.495 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 4 | 0.05 picogram | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 7 | 0.20 picogram | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) | Day 8 | 0.10 picogram | Standard Deviation 0.141 |
Primary
Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV)
The change from baseline data for hematology parameter MCV, was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 4 | 0.15 femtoliters | Standard Deviation 0.698 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 8 | 0.13 femtoliters | Standard Deviation 0.333 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 7 | -0.10 femtoliters | Standard Deviation 0.341 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Follow-up | 0.47 femtoliters | Standard Deviation 0.753 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 2 | 0.27 femtoliters | Standard Deviation 1.109 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Follow-up | -0.50 femtoliters | Standard Deviation 0.566 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 2 | -0.10 femtoliters | Standard Deviation 0.99 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 4 | -0.20 femtoliters | Standard Deviation 0.99 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 7 | -0.40 femtoliters | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) | Day 8 | -0.15 femtoliters | Standard Deviation 0.354 |
Primary
Change From Baseline in Hematology Paramaters- Platelet Count
The data for hematology parameter platelet count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Platelet Count | Day 4 | 5.0 per cubic millimeter | Standard Deviation 18.34 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Platelet Count | Day 8 | 29.3 per cubic millimeter | Standard Deviation 21.04 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Platelet Count | Day 7 | 18.5 per cubic millimeter | Standard Deviation 19.77 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Platelet Count | Follow-up | 23.3 per cubic millimeter | Standard Deviation 6.5 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Platelet Count | Day 2 | -5.7 per cubic millimeter | Standard Deviation 24.86 |
| Placebo | Change From Baseline in Hematology Paramaters- Platelet Count | Follow-up | -1.0 per cubic millimeter | Standard Deviation 33.94 |
| Placebo | Change From Baseline in Hematology Paramaters- Platelet Count | Day 2 | 3.0 per cubic millimeter | Standard Deviation 9.9 |
| Placebo | Change From Baseline in Hematology Paramaters- Platelet Count | Day 4 | -23.5 per cubic millimeter | Standard Deviation 37.48 |
| Placebo | Change From Baseline in Hematology Paramaters- Platelet Count | Day 7 | 2.5 per cubic millimeter | Standard Deviation 10.61 |
| Placebo | Change From Baseline in Hematology Paramaters- Platelet Count | Day 8 | 2.0 per cubic millimeter | Standard Deviation 2.83 |
Primary
Change From Baseline in Hematology Paramaters- Red Blood Cell Count
The data for hematology parameter red blood cell count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 4 | -0.112 million cells per microliter | Standard Deviation 0.2601 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 8 | -0.170 million cells per microliter | Standard Deviation 0.1764 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 7 | -0.083 million cells per microliter | Standard Deviation 0.2947 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Follow-up | -0.343 million cells per microliter | Standard Deviation 0.23 |
| GSK2248761 30 mg | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 2 | -0.153 million cells per microliter | Standard Deviation 0.1129 |
| Placebo | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Follow-up | -0.375 million cells per microliter | Standard Deviation 0.1344 |
| Placebo | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 2 | -0.240 million cells per microliter | Standard Deviation 0.0283 |
| Placebo | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 4 | 0.200 million cells per microliter | Standard Deviation 0.4525 |
| Placebo | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 7 | -0.190 million cells per microliter | Standard Deviation 0.0707 |
| Placebo | Change From Baseline in Hematology Paramaters- Red Blood Cell Count | Day 8 | -0.170 million cells per microliter | Standard Deviation 0.1556 |
Primary
Change From Baseline in Hematology Parameters- Total Neutrophil
The data for hematology parameter total neutrophil count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 4 | 508.3 giga cells per liter | Standard Deviation 692.05 |
| GSK2248761 30 mg | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 8 | 296.7 giga cells per liter | Standard Deviation 535.82 |
| GSK2248761 30 mg | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 7 | -30.0 giga cells per liter | Standard Deviation 750.55 |
| GSK2248761 30 mg | Change From Baseline in Hematology Parameters- Total Neutrophil | Follow-up | 76.7 giga cells per liter | Standard Deviation 433.34 |
| GSK2248761 30 mg | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 2 | 243.3 giga cells per liter | Standard Deviation 499.83 |
| Placebo | Change From Baseline in Hematology Parameters- Total Neutrophil | Follow-up | 105.0 giga cells per liter | Standard Deviation 2142.53 |
| Placebo | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 2 | 980.0 giga cells per liter | Standard Deviation 1753.62 |
| Placebo | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 4 | -375.0 giga cells per liter | Standard Deviation 21.21 |
| Placebo | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 7 | -745.0 giga cells per liter | Standard Deviation 49.5 |
| Placebo | Change From Baseline in Hematology Parameters- Total Neutrophil | Day 8 | -705.0 giga cells per liter | Standard Deviation 374.77 |
Primary
Change From Baseline in HR
Vital sign measurements for HR after sitting for 5 minutes were measured. The average mean values were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 1 (4-hour), Day 4 (Pre-dose and 4 hour), Day 7 (pre-dose and 4-hour), Day 8 and follow up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in HR | HR, Day 4, 4 hour | -2.2 Beats per minute | Standard Deviation 3.92 |
| GSK2248761 30 mg | Change From Baseline in HR | HR, Day 7, 4 hour | -0.3 Beats per minute | Standard Deviation 4.63 |
| GSK2248761 30 mg | Change From Baseline in HR | HR, Day 4, Pre-dose | -2.7 Beats per minute | Standard Deviation 6.12 |
| GSK2248761 30 mg | Change From Baseline in HR | HR, Day 8 | 3.7 Beats per minute | Standard Deviation 7.42 |
| GSK2248761 30 mg | Change From Baseline in HR | HR, Day 7, Pre-dose | 3.0 Beats per minute | Standard Deviation 7.54 |
| GSK2248761 30 mg | Change From Baseline in HR | HR, Follow-up | -0.3 Beats per minute | Standard Deviation 5.99 |
| GSK2248761 30 mg | Change From Baseline in HR | HR , Day 1, 4 hour | -2.5 Beats per minute | Standard Deviation 6.5 |
| Placebo | Change From Baseline in HR | HR, Follow-up | 5.0 Beats per minute | Standard Deviation 11.31 |
| Placebo | Change From Baseline in HR | HR , Day 1, 4 hour | -3.0 Beats per minute | Standard Deviation 4.24 |
| Placebo | Change From Baseline in HR | HR, Day 4, Pre-dose | -6.0 Beats per minute | Standard Deviation 11.31 |
| Placebo | Change From Baseline in HR | HR, Day 4, 4 hour | -6.0 Beats per minute | Standard Deviation 21.21 |
| Placebo | Change From Baseline in HR | HR, Day 7, Pre-dose | -1.0 Beats per minute | Standard Deviation 22.63 |
| Placebo | Change From Baseline in HR | HR, Day 7, 4 hour | -2.5 Beats per minute | Standard Deviation 17.68 |
| Placebo | Change From Baseline in HR | HR, Day 8 | 0.0 Beats per minute | Standard Deviation 12.73 |
Primary
Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Vital sign measurements for SBP and DBP after sitting for 5 minutes were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose \[Screening, Day -1 or Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 1, 4, 7 , Day 8 and Follow-up (Day 14)
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 4 hour | 4.3 millimeters of mercury | Standard Deviation 6.35 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 4, Pre-dose | -0.7 millimeters of mercury | Standard Deviation 5.92 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 4, 4 hour | 3.0 millimeters of mercury | Standard Deviation 11.7 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, Pre-dose | 6.2 millimeters of mercury | Standard Deviation 6.94 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 4 hour | 9.8 millimeters of mercury | Standard Deviation 2.71 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 8 | 8.5 millimeters of mercury | Standard Deviation 7.48 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Follow-up | 5.8 millimeters of mercury | Standard Deviation 7.33 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 4 hour | 8.2 millimeters of mercury | Standard Deviation 8.16 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 4, Pre-dose | 5.8 millimeters of mercury | Standard Deviation 16.58 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 4, 4 hour | 9.7 millimeters of mercury | Standard Deviation 10.21 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, Pre-dose | 8.2 millimeters of mercury | Standard Deviation 10.96 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 4 hour | 6.0 millimeters of mercury | Standard Deviation 9.8 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 8 | 5.2 millimeters of mercury | Standard Deviation 10.25 |
| GSK2248761 30 mg | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Follow-up | 4.5 millimeters of mercury | Standard Deviation 9.07 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, Pre-dose | 7.0 millimeters of mercury | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 4 hour | -4.5 millimeters of mercury | Standard Deviation 14.85 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 4 hour | 1.0 millimeters of mercury | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 4, Pre-dose | 0.5 millimeters of mercury | Standard Deviation 17.68 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 8 | 15.0 millimeters of mercury | Standard Deviation 9.9 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 4, 4 hour | 12.5 millimeters of mercury | Standard Deviation 14.85 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 4, Pre-dose | 1.0 millimeters of mercury | Standard Deviation 15.56 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, Pre-dose | 6.5 millimeters of mercury | Standard Deviation 9.19 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 4 hour | 8.0 millimeters of mercury | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 4 hour | 14.5 millimeters of mercury | Standard Deviation 12.02 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 4, 4 hour | 3.0 millimeters of mercury | Standard Deviation 12.73 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 8 | 13.5 millimeters of mercury | Standard Deviation 19.09 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Follow-up | 8.0 millimeters of mercury | Standard Deviation 5.66 |
| Placebo | Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Follow-up | 14.5 millimeters of mercury | Standard Deviation 6.36 |
Primary
Change From Baseline Through Day 8 in Plasma HIV-1 RNA
The quantitative analysis of plasma was done to evaluate the amount of HIV-1 RNA at Day 1,2,3,4,5,6,7, 8 and End of treatment visit. The quantification was done using a Polymerase chain reactor (PCR). The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose Day 1) to Day 8
Population: The Intent-to-treat Exposed (ITT) Population was defined as all participants who met the study criteria and were randomized into the study with documented evidence of having received at least 1 dose of randomized treatment and at least one post-baseline HIV-1 RNA measurement and have Day 1 HIV-RNA\>1500 copies/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline Through Day 8 in Plasma HIV-1 RNA | -0.967 log 10 copies per milliliter (mL) | Standard Deviation 0.3988 |
| Placebo | Change From Baseline Through Day 8 in Plasma HIV-1 RNA | -0.036 log 10 copies per milliliter (mL) | Standard Deviation 0.2495 |
p-value: 0.04295% CI: [-1.812, -0.053]ANCOVA
Primary
Change From Baseline to Nadir in Plasma HIV-1 RNA
The quantification of plasma HIV-1 RNA, was conducted for the change from baseline to on treatment nadir (maximum change) before starting HAART or Kaletra monotherapy on Day 8. The quantification was done using a PCR. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1\]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Time frame: Baseline (pre-dose Day 1) to Day 8
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2248761 30 mg | Change From Baseline to Nadir in Plasma HIV-1 RNA | -1.019 log10 copies/mL | Standard Deviation 0.3687 |
| Placebo | Change From Baseline to Nadir in Plasma HIV-1 RNA | -0.580 log10 copies/mL | Standard Deviation 0.0157 |
p-value: 0.22195% CI: [-1.173, 0.347]ANCOVA
Primary
GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24])
AUC (0-24), measured the plasma concentration of GSK2248761 against time, from time zero (pre-dose) to 24 hrs post-dose AUC (0-24) and from time zero to extrapolated infinite time AUC (0-∞). Serial blood samples were collected on Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Time frame: Day 1 (Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
Population: The PK Concentration Population included all participants who received GSK22648761 and underwent plasma PK sampling during the study. Participants for whom a plasma PK sample was obtained and assayed were included in the listing of plasma GSK2248761 concentration-time data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24]) | AUC(0-inf) | 2217.73 hours*nanograms (ng)/mL | Geometric Coefficient of Variation 45 |
| GSK2248761 30 mg | GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24]) | AUC(0-24) | 1842.19 hours*nanograms (ng)/mL | Geometric Coefficient of Variation 41 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F)
The Clearance factor was defined as the volume of plasma cleared of the drug GSK2248761, per unit time. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
Population: PK population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F) | 13.53 liter per hour | Geometric Coefficient of Variation 45 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24)
Cmax represents the maximum concentration of GSK2248761 in the plasma. C24 is defined as the measure of plasma drug concentration of GSK2248761, 24 hours post dose, determined on Day 1. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.Data for dose normalized Cmax and C24 was reported.
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours)
Population: PK population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) | Cmax | 585.43 ng/mL | Geometric Coefficient of Variation 39 |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) | C24 | 103.40 ng/mL | Geometric Coefficient of Variation 61 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag)
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 1. The t1/2 was defined as the time measured for plasma concentration to decrease by one half. The tlag was defined as the time taken for the drug GSK2248761, to appear in the systemic circulation following administration. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
Population: PK population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag) | tmax | 4.00 hour |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag) | t1/2 | 7.99 hour |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag) | tlag | 0.49 hour |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ)
AUC(0-τ) is the AUC to the end of dosing period. For Day 7, it is the AUC measured at the end of the dosing period at Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
Time frame: Day 7 (Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
Population: PK population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ) | 9679.71 hour*ng/mL | Geometric Coefficient of Variation 54 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax
The C0 was defined as the concentration of drug in plasma, before dose administration on Day 7. Cτ, was defined as the concentration of drug in the plasma at the end of dosing interval. The Cmin was defined as the minimum concentration of the drug in plasma during one dosing interval on Day 7. Cmax represents the maximum concentration of GSK2248761 in the plasma on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
Time frame: Day 7 (Pre -dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
Population: PK population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax | C0, Day 7 | 57.47 ng/mL | Geometric Coefficient of Variation 83 |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax | Cτ, Day 7 | 54.27 ng/mL | Geometric Coefficient of Variation 75 |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax | Cmin, Day 7 | 46.37 ng/mL | Geometric Coefficient of Variation 83 |
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax | Cmax, Day 7 | 212.93 ng/mL | Geometric Coefficient of Variation 41 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2
The t1/2 was defined as the time measured for plasma concentration to decrease by one half. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
Time frame: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2 | 9.69 hour | Geometric Coefficient of Variation 25 |
Primary
GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
Time frame: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
Population: PK population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2248761 30 mg | GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax | 4.01 hours |
Primary
HIV-1 Rate of Decline by Treatment
The rate of decrease in the viral load of HIV-1 virus in response to individual treatment was measured. The viral load data was assumed to have a log normal prior distribution and followed linear decline with non-informative conjugate prior densities. The rate of decline (slope of the day) for each treatment was measured using a PCR from Day 1 to Day 8. The slope has been reported as mean.
Time frame: Day 1 to Day 8
Population: ITT population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GSK2248761 30 mg | HIV-1 Rate of Decline by Treatment | -0.1243 log10 copies/mL |
| Placebo | HIV-1 Rate of Decline by Treatment | 0.0189 log10 copies/mL |
Comparison: Day 1 to Day 8p-value: <0.0001Mixed Models Analysis
Comparison: Placebo, Day 1 to Day 8p-value: 0.6922Mixed Models Analysis
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Triplicate 12-lead ECGs were collected at different timepoints, after participants were supine for 5 minutes, during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. The three consecutive determinations were collected 5 plus or minus 2 minutes apart and all three tracings were recorded. The participants with abnormal values categorized as abnormal clinically significant (CS) and not clinically significant (NCS) were reported.
Time frame: Day 1, Day 4, Day 7, Day 8 and follow-up
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, Pre-dose, NCS | 2 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, Pre-dose, NCS | 3 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, 8 hour, NCS | 2 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, 4 hour, NCS | 3 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, 4 hour, NCS | 2 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, 8 hour, NCS | 2 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, 4 hour, NCS | 2 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 8, Pre-dose, NCS | 3 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, 8 hour, NCS | 3 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Follow-up, NCS | 3 Participants |
| GSK2248761 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, Pre-dose, NCS | 3 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Follow-up, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, Pre-dose, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, 4 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 1, 8 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, Pre-dose, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, 4 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 4, 8 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, Pre-dose, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, 4 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 7, 8 hour, NCS | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 8, Pre-dose, NCS | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
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.
Time frame: Up to 38 days
Population: Safety population was defined as all participants who were randomized into the study with documented evidence of receipt of at least one dose of randomized treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2248761 30 mg | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any AE | 4 Participants |
| GSK2248761 30 mg | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any SAE | 0 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any AE | 1 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any SAE | 0 Participants |
Secondary
Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration
The accumulation ratio is based on the parameters, Cmax, AUC(0-tau), AUC(0-24), C(tau), C24, AND AUC(0-inf). The accumulation ratio Ro was the ratio of AUC(0-tau) on Day 7 to that of AUC(0-24) on Day 1; the accumulation ratio R (Cmax) was the ratio of Cmax on Day 7 to that of Cmax on Day 1; the accumulation ratio R(Ctau) was the ratio of Ctau on Day 7 to the ratio of C24 on Day 1 and the Time Invariance Ratio Rs was defined as the ratio of AUC(0-tau) on Day 7 to that of AUC(0-inf) on Day 1. The ratio has been reported as number.
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) on Day 1 and Day 7
Population: PK population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2248761 30 mg | Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration | Accumulation Ratio Ro | 1.576 ratio |
| GSK2248761 30 mg | Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration | Accumulation Ratio R [Cmax] | 1.212 ratio |
| GSK2248761 30 mg | Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration | Accumulation Ratio R[Ctau] | 1.750 ratio |
| GSK2248761 30 mg | Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration | Time Invariance Ratio Rs | 1.309 ratio |
Secondary
Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7
The pre-dose GSK2248761 steady state concentration, following repeated dose administration from Day 2 through Day 7 was assessed. Serial dose sampling was done on each day of Day 2, 3, 4, 5 and Day 6 and for Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose), before the administration of the study drug daily.
Time frame: Day 7 (Pre - dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) and Days 2, 3, 4. 5 and 6: pre-dose only
Population: PK population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| GSK2248761 30 mg | Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7 | Days 4, 5, 6 and 7 | 0.052 ng/mL |
| GSK2248761 30 mg | Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7 | Days 5, 6 and 7 | -0.019 ng/mL |
| GSK2248761 30 mg | Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7 | Days 6 and 7 | -0.056 ng/mL |
Secondary
Change From Baseline in Reverse Transcriptase Sequences of HIV-1 at Day 8
None of the participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations at codons 90, 98, 100, 101, 103, 106, 108, 138, 179, 181, 188, 190, 225, or 230 at either Day 1 or Day 8. No mutation selected by GSK2248761 in vitro was observed for any participant at either Day 1 or Day 8. This data for Change from baseline in reverse transcriptase sequences of HIV-1 at Day 8 not collected.
Time frame: Baseline (Screening) and Day 8
Population: ITT population. Data not collected for Change from baseline reverse transcriptase sequence
Secondary
Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8
Data for CD4+ and CD8+ cells was collected at Screening, Day 1 and Day 8. The percent change from baseline was reported at Day 1 and Day 8. Baseline was defined as Screening. The percent change from baseline was calculated as post-randomization value minus the baseline value.
Time frame: Baseline (Screening), Day 1 and Day 8
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD4+, Day 1 | -3.2 Percent change | Standard Deviation 1.78 |
| GSK2248761 30 mg | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD8+, Day 1 | -2.8 Percent change | Standard Deviation 7.31 |
| GSK2248761 30 mg | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD4+, Day 8 | -2.4 Percent change | Standard Deviation 1.49 |
| GSK2248761 30 mg | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD8+, Day 8 | -0.4 Percent change | Standard Deviation 2.56 |
| Placebo | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD4+, Day 8 | -1.7 Percent change | Standard Deviation 0.42 |
| Placebo | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD4+, Day 1 | -2.9 Percent change | Standard Deviation 1.27 |
| Placebo | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD8+, Day 8 | 0.4 Percent change | Standard Deviation 1.41 |
| Placebo | Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 | CD8+, Day 1 | 2.8 Percent change | Standard Deviation 3.82 |
Secondary
PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality
Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. Data for Ctau on Day 1 is presented for concentration at 24 hours post-dose on Day 1.
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7
Population: PK population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 1 | 175.63 ng/mL | Geometric Coefficient of Variation 39 |
| GSK2248761 30 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 7 | 212.93 ng/mL | Geometric Coefficient of Variation 41 |
| GSK2248761 30 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 1 | 31.02 ng/mL | Geometric Coefficient of Variation 61 |
| GSK2248761 30 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 7 | 54.27 ng/mL | Geometric Coefficient of Variation 75 |
| Placebo | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 1 | 797.8 ng/mL | Geometric Coefficient of Variation 32.19 |
| Placebo | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 7 | 204.7 ng/mL | Geometric Coefficient of Variation 48.36 |
| Placebo | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 7 | 960.1 ng/mL | Geometric Coefficient of Variation 22.62 |
| Placebo | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 1 | 128.9 ng/mL | Geometric Coefficient of Variation 37.36 |
| IDX899 200 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 7 | 469.2 ng/mL | Geometric Coefficient of Variation 63.17 |
| IDX899 200 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 7 | 2158.9 ng/mL | Geometric Coefficient of Variation 35.96 |
| IDX899 200 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 1 | 325.6 ng/mL | Geometric Coefficient of Variation 60.93 |
| IDX899 200 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 1 | 1686.2 ng/mL | Geometric Coefficient of Variation 24.67 |
| IDX899 400 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 1 | 2625.9 ng/mL | Geometric Coefficient of Variation 34.2 |
| IDX899 400 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 7 | 4140.7 ng/mL | Geometric Coefficient of Variation 21.54 |
| IDX899 400 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 7 | 864.5 ng/mL | Geometric Coefficient of Variation 47.44 |
| IDX899 400 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 1 | 422.9 ng/mL | Geometric Coefficient of Variation 81.23 |
| IDX899 800 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 7 | 540.3 ng/mL | Geometric Coefficient of Variation 124.71 |
| IDX899 800 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Ctau, Day 1 | 364.5 ng/mL | Geometric Coefficient of Variation 123.77 |
| IDX899 800 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 7 | 5394.5 ng/mL | Geometric Coefficient of Variation 46.36 |
| IDX899 800 mg | PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality | Cmax, Day 1 | 3406.4 ng/mL | Geometric Coefficient of Variation 31.31 |
Secondary
PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality
Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. The dose proportionality effects of IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg, following repeat dose administration on Day 7 for the PK parameter AUC(0-tau) has been reported.
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7
Population: PK population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2248761 30 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-inf), Day 1 | 2217.73 hour*ng/mL | Geometric Coefficient of Variation 45 |
| GSK2248761 30 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-tau), Day 7 | 2903.91 hour*ng/mL | Geometric Coefficient of Variation 54 |
| Placebo | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-inf), Day 1 | 9908 hour*ng/mL | Geometric Coefficient of Variation 21.07 |
| Placebo | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-tau), Day 7 | 11650 hour*ng/mL | Geometric Coefficient of Variation 31.02 |
| IDX899 200 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-inf), Day 1 | 23817 hour*ng/mL | Geometric Coefficient of Variation 46.77 |
| IDX899 200 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-tau), Day 7 | 27209 hour*ng/mL | Geometric Coefficient of Variation 47.46 |
| IDX899 400 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-tau), Day 7 | 49649 hour*ng/mL | Geometric Coefficient of Variation 26.55 |
| IDX899 400 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-inf), Day 1 | 33820 hour*ng/mL | Geometric Coefficient of Variation 58.3 |
| IDX899 800 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-inf), Day 1 | 37812 hour*ng/mL | Geometric Coefficient of Variation 81.37 |
| IDX899 800 mg | PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality | AUC(0-tau), Day 7 | 53683 hour*ng/mL | Geometric Coefficient of Variation 72.34 |