A Phase 2 interventional study of GSK2248761 and Lopinavir/ritonavir in Infection, Human Immunodeficiency Virus, sponsored by ViiV Healthcare. Completed at 1 site in Argentina. Open to participants aged 21 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-11-29.
Sponsored by ViiV Healthcare · Phase 2, Interventional, and Treatment
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.
2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.
This study's enrollment of 8 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.
Browse Acquired Immunodeficiency Syndrome studies →ViiV Healthcare is the lead sponsor of 261 studies on the registry; 16 are open to participants now.
Of its 66 completed or terminated interventional studies of FDA-regulated products, 50 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Note: Study drugs include GSK2248761 placebo or the follow-up HAART or Kaletra therapy.
In Cohort 1 subjects will receive either GSK2248761 30 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART.
Drug: GSK2248761 · Drug: Lopinavir/ritonavir · Drug: HAART · Drug: Placebo
In Cohort 2 subjects will receive either GSK2248761 in the range of 10 mg - 20 mg or 40 mg - 90 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART. The dose for Cohort 2 will be determined following evaluation of results from Cohort 1. Cohort 2 may not be done.
Drug: Lopinavir/ritonavir · Drug: HAART · Drug: Placebo · Drug: GSK2248761
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.
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.
Also known as: Kaletra
Highly Active Antiretroviral therapy of the doctor's choice.
Placebo is a capsule with no drug in it.
GSK2248761 10 mg -20 mg or 40 mg - 90 mg 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.
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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)
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)
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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.
| Milestone | GSK2248761 30 mg | Placebo |
|---|---|---|
| Started | 6 | 2 |
| Completed | 6 | 2 |
| Not completed | 0 | 0 |
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.
| Participants | GSK2248761 30 mg | Placebo |
|---|---|---|
| Any AE | 4 | 1 |
| Any SAE | 0 | 0 |
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.
| thousand cells per microliter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Basophils, Day 2 | -1.7 ± 4.08 | -5.0 ± 7.07 |
| Basophils, Day 4 | 8.3 ± 9.83 | 5.0 ± 7.07 |
| Basophils, Day 7 | 1.7 ± 7.53 | -10.0 ± 14.14 |
| Basophils, Day 8 | 3.3 ± 8.16 | -10.0 ± 14.14 |
| Basophils, Follow-Up | -3.3 ± 10.33 | -15.0 ± 7.07 |
| Eosinophils, Day 2 | -1.7 ± 35.45 | -120.0 ± 141.42 |
| Eosinophils, Day 4 | -60.0 ± 150.33 | -20.0 ± 0.00 |
| Eosinophils, Day 7 | -38.3 ± 106.85 | -50.0 ± 28.28 |
| Eosinophils, Day 8 | -96.7 ± 229.49 | -80.0 ± 70.71 |
| Eosinophils, Follow-Up | -63.3 ± 153.84 | -135.0 ± 162.63 |
| Lymphocytes, Day 2 | -120.0 ± 272.18 | 315.0 ± 1067.73 |
| Lymphocytes, Day 4 | 268.3 ± 298.83 | 260.0 ± 296.98 |
| Lymphocytes, Day 7 | 126.7 ± 415.44 | 180.0 ± 410.12 |
| Lymphocytes, Day 8 | 273.3 ± 357.64 | 480.0 ± 1060.66 |
| Lymphocytes, Follow-Up | -110.0 ± 375.34 | 50.0 ± 551.54 |
| Monocytes, Day 2 | 28.3 ± 71.11 | 125.0 ± 176.78 |
| Monocytes, Day 4 | 33.3 ± 76.59 | 120.0 ± 155.56 |
| Monocytes, Day 7 | -15.0 ± 135.17 | 25.0 ± 77.78 |
| Monocytes, Day 8 | 23.3 ± 103.67 | 75.0 ± 134.35 |
| Monocytes, Follow-Up | 10.0 ± 143.67 | -115.0 ± 35.36 |
| White blood cell, Day 2 | 148.3 ± 649.78 | 1295.0 ± 2849.64 |
| White blood cell, Day 4 | 758.3 ± 896.78 | -10.0 ± 155.56 |
| White blood cell, Day 7 | 45.0 ± 1017.70 | -600.0 ± 367.70 |
| White blood cell, Day 8 | 500.0 ± 776.79 | -240.0 ± 1513.21 |
| White blood cell, Follow-Up | -90.0 ± 699.29 | -110.0 ± 2573.87 |
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.
| gram per decilitre | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | -0.40 ± 0.316 | -0.50 ± 0.283 |
| Day 4 | -0.28 ± 0.794 | 0.60 ± 1.273 |
| Day 7 | -0.25 ± 0.864 | -0.45 ± 0.071 |
| Day 8 | -0.48 ± 0.585 | -0.45 ± 0.354 |
| Follow-up | -0.93 ± 0.550 | -1.00 ± 0.424 |
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.
| per cubic millimeter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | -5.7 ± 24.86 | 3.0 ± 9.90 |
| Day 4 | 5.0 ± 18.34 | -23.5 ± 37.48 |
| Day 7 | 18.5 ± 19.77 | 2.5 ± 10.61 |
| Day 8 | 29.3 ± 21.04 | 2.0 ± 2.83 |
| Follow-up | 23.3 ± 6.50 | -1.0 ± 33.94 |
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.
| million cells per microliter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | -0.153 ± 0.1129 | -0.240 ± 0.0283 |
| Day 4 | -0.112 ± 0.2601 | 0.200 ± 0.4525 |
| Day 7 | -0.083 ± 0.2947 | -0.190 ± 0.0707 |
| Day 8 | -0.170 ± 0.1764 | -0.170 ± 0.1556 |
| Follow-up | -0.343 ± 0.2300 | -0.375 ± 0.1344 |
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.
| giga cells per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | 243.3 ± 499.83 | 980.0 ± 1753.62 |
| Day 4 | 508.3 ± 692.05 | -375.0 ± 21.21 |
| Day 7 | -30.0 ± 750.55 | -745.0 ± 49.50 |
| Day 8 | 296.7 ± 535.82 | -705.0 ± 374.77 |
| Follow-up | 76.7 ± 433.34 | 105.0 ± 2142.53 |
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.
| picogram | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | 0.07 ± 0.197 | 0.45 ± 0.495 |
| Day 4 | 0.08 ± 0.147 | 0.05 ± 0.071 |
| Day 7 | 0.03 ± 0.320 | 0.20 ± 0.283 |
| Day 8 | 0.07 ± 0.151 | 0.10 ± 0.141 |
| Follow-up | 0.13 ± 0.367 | 0.25 ± 0.071 |
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.
| femtoliters | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | 0.27 ± 1.109 | -0.10 ± 0.990 |
| Day 4 | 0.15 ± 0.698 | -0.20 ± 0.990 |
| Day 7 | -0.10 ± 0.341 | -0.40 ± 0.283 |
| Day 8 | 0.13 ± 0.333 | -0.15 ± 0.354 |
| Follow-up | 0.47 ± 0.753 | -0.50 ± 0.566 |
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.
| percentage of red blood cells | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | -1.22 ± 1.286 | -2.15 ± 0.212 |
| Day 4 | -0.92 ± 2.110 | 1.70 ± 3.536 |
| Day 7 | -0.80 ± 2.563 | -1.85 ± 0.495 |
| Day 8 | -1.45 ± 1.508 | -1.55 ± 1.202 |
| Follow-up | -2.78 ± 1.907 | -3.55 ± 0.919 |
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.
| percentage of red blood cells | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 2 | 0.02 ± 0.445 | 0.55 ± 0.778 |
| Day 4 | 0.05 ± 0.373 | 0.15 ± 0.212 |
| Day 7 | 0.07 ± 0.361 | 0.40 ± 0.283 |
| Day 8 | 0.02 ± 0.214 | 0.15 ± 0.212 |
| Follow-up | -0.03 ± 0.301 | 0.45 ± 0.212 |
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.
| gram per deciliter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Albumin, Day 2 | -0.17 ± 0.207 | -0.20 ± 0.000 |
| Albumin, Day 4 | -0.08 ± 0.248 | 0.00 ± 0.000 |
| Albumin, Day 7 | -0.10 ± 0.283 | -0.05 ± 0.212 |
| Albumin, Day 8 | -0.05 ± 0.383 | -0.10 ± 0.000 |
| Albumin, Follow-up | -0.07 ± 0.137 | 0.05 ± 0.071 |
| Total protein, Day 2 | -0.45 ± 0.302 | -0.55 ± 0.212 |
| Total protein, Day 4 | -0.10 ± 0.385 | -0.10 ± 0.283 |
| Total protein, Day 7 | 0.10 ± 0.494 | 0.05 ± 0.071 |
| Total protein, Day 8 | 0.00 ± 0.636 | -0.25 ± 0.071 |
| Total protein, Follow-up | -0.30 ± 0.268 | -0.20 ± 0.283 |
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.
| milligram per deciliter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Blood urea nitrogen, Day 2 | 1.5 ± 7.20 | -1.0 ± 2.83 |
| Blood urea nitrogen, Day 4 | 4.3 ± 5.32 | 4.0 ± 5.66 |
| Blood urea nitrogen, Day 7 | 1.0 ± 7.67 | 3.5 ± 2.12 |
| Blood urea nitrogen, Day 8 | 2.7 ± 6.38 | 5.5 ± 9.19 |
| Blood urea nitrogen, Follow-up | -2.2 ± 7.41 | 1.0 ± 15.56 |
| Triglycerides, Day 2 | -17.8 ± 19.05 | 5.0 ± 14.14 |
| Triglycerides, Day 4 | -19.8 ± 16.47 | 5.5 ± 4.95 |
| Triglycerides, Day 7 | 5.2 ± 21.44 | 20.5 ± 27.58 |
| Triglycerides, Day 8 | 20.8 ± 63.05 | 34.0 ± 21.21 |
| Triglycerides, Follow-up | -3.0 ± 12.63 | 114.0 ± 8.49 |
| Glucose, Day 2 | 1.3 ± 9.18 | 6.0 ± 4.24 |
| Glucose, Day 4 | 0.0 ± 10.92 | -0.5 ± 12.02 |
| Glucose, Day 7 | -1.8 ± 7.86 | -1.0 ± 1.41 |
| Glucose, Day 8 | -5.2 ± 10.72 | -5.0 ± 2.83 |
| Glucose, Follow-up | 3.0 ± 5.76 | 10.0 ± 4.24 |
| Creatinine, Day 2 | -0.048 ± 0.0770 | 0.000 ± 0.0000 |
| Creatinine, Day 4 | 0.025 ± 0.0586 | 0.025 ± 0.0071 |
| Creatinine, Day 7 | -0.003 ± 0.0455 | 0.035 ± 0.0919 |
| Creatinine, Day 8 | -0.060 ± 0.0569 | -0.040 ± 0.1273 |
| Creatinine, Follow-up | -0.003 ± 0.1183 | 0.060 ± 0.1273 |
| Calcium, Day 2 | -0.25 ± 0.176 | -0.25 ± 0.071 |
| Calcium, Day 4 | -0.13 ± 0.301 | 0.05 ± 0.071 |
| Calcium, Day 7 | -0.40 ± 0.322 | -0.20 ± 0.141 |
| Calcium, Day 8 | -0.47 ± 0.418 | -0.45 ± 0.354 |
| Calcium, Follow-up | 0.08 ± 0.299 | 0.05 ± 0.071 |
| Cholesterol, Day 2 | -11.8 ± 13.92 | -12.0 ± 8.49 |
| Cholesterol, Day 4 | -15.3 ± 28.72 | -17.5 ± 10.61 |
| Cholesterol, Day 7 | -12.0 ± 35.25 | -20.5 ± 7.78 |
| Cholesterol, Day 8 | -8.3 ± 41.15 | -13.5 ± 0.71 |
| Cholesterol, Follow-up | -5.5 ± 33.44 | -0.5 ± 17.68 |
| Total bilirubin, Day 2 | -0.12 ± 0.160 | -0.10 ± 0.141 |
| Total bilirubin, Day 4 | -0.08 ± 0.133 | -0.15 ± 0.071 |
| Total bilirubin, Day 7 | -0.03 ± 0.121 | -0.05 ± 0.071 |
| Total bilirubin, Day 8 | -0.08 ± 0.075 | -0.10 ± 0.000 |
| Total bilirubin, Follow-up | 0.08 ± 0.240 | 0.00 ± 0.000 |
| Direct bilirubin, Day 2 | -0.08 ± 0.041 | 0.00 ± 0.000 |
| Direct bilirubin, Day 4 | -0.08 ± 0.041 | 0.00 ± 0.000 |
| Direct bilirubin, Day 7 | -0.05 ± 0.055 | 0.05 ± 0.071 |
| Direct bilirubin, Day 8 | -0.05 ± 0.055 | 0.00 ± 0.000 |
| Direct bilirubin, Follow-up | 0.02 ± 0.075 | 0.10 ± 0.000 |
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.
| International units (IU) per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Alkaline phosphatase, Day 2 | -5.8 ± 7.14 | -16.0 ± 0.00 |
| Alkaline phosphatase, Day 4 | -1.5 ± 10.33 | -16.0 ± 8.49 |
| Alkaline phosphatase, Day 7 | 1.8 ± 10.83 | -7.5 ± 4.95 |
| Alkaline phosphatase, Day 8 | 3.3 ± 14.88 | -14.5 ± 6.36 |
| Alkaline phosphatase, Follow-up | 4.2 ± 24.96 | -9.5 ± 0.71 |
| Alanine amino transferase, Day 2 | -3.0 ± 6.63 | 0.5 ± 6.36 |
| Alanine amino transferase, Day 4 | -2.0 ± 15.02 | -3.5 ± 4.95 |
| Alanine amino transferase, Day 7 | 1.7 ± 21.81 | -3.5 ± 4.95 |
| Alanine amino transferase, Day 8 | 3.7 ± 24.40 | 0.0 ± 5.66 |
| Alanine amino transferase, Follow-up | -7.2 ± 21.81 | -1.5 ± 6.36 |
| Aspartate amino transferase, Day 2 | 0.8 ± 4.17 | 1.0 ± 1.41 |
| Aspartate amino transferase, Day 4 | -0.2 ± 7.31 | -4.5 ± 3.54 |
| Aspartate amino transferase, Day 7 | -0.3 ± 7.69 | -3.0 ± 8.49 |
| Aspartate amino transferase, Day 8 | 1.7 ± 9.40 | 0.0 ± 5.66 |
| Aspartate amino transferase, Follow-up | -0.2 ± 8.40 | 2.5 ± 4.95 |
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.
| milliequivalents per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Sodium, Day 2 | -1.2 ± 1.17 | -0.5 ± 2.12 |
| Sodium, Day 4 | -0.8 ± 1.60 | 1.0 ± 1.41 |
| Sodium, Day 7 | -1.5 ± 1.64 | 0.0 ± 0.00 |
| Sodium, Day 8 | -1.7 ± 1.51 | -0.5 ± 0.71 |
| Sodium, Follow-up | 2.3 ± 1.63 | 1.0 ± 1.41 |
| Potassium, Day 2 | -0.02 ± 0.293 | -0.25 ± 0.071 |
| Potassium, Day 4 | 0.10 ± 0.434 | 0.10 ± 0.566 |
| Potassium, Day 7 | -0.17 ± 0.314 | -0.10 ± 0.000 |
| Potassium, Day 8 | -0.18 ± 0.371 | -0.00 ± 0.141 |
| Potassium, Follow-up | -0.08 ± 0.360 | -0.30 ± 0.424 |
| Carbondioxide, Day 2 | -0.80 ± 2.384 | -1.35 ± 2.051 |
| Carbondioxide, Day 4 | 3.17 ± 1.488 | 2.70 ± 4.101 |
| Carbondioxide, Day 7 | 2.93 ± 1.850 | 3.60 ± 2.121 |
| Carbondioxide, Day 8 | 0.87 ± 2.471 | 1.65 ± 1.768 |
| Carbondioxide, Follow-up | 2.03 ± 2.187 | -0.30 ± 1.131 |
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.
| millimole per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Phosphorus, Day 2 | -0.05 ± 0.524 | -0.80 ± 0.707 |
| Phosphorus, Day 4 | 0.07 ± 0.799 | 0.25 ± 0.212 |
| Phosphorus, Day 7 | -0.17 ± 0.628 | -0.00 ± 0.141 |
| Phosphorus, Day 8 | -0.27 ± 0.662 | -0.35 ± 0.071 |
| Phosphorus, Follow-up | -0.58 ± 0.634 | -0.95 ± 0.071 |
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.
| Micromole per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Uric acid, Day 2 | 0.27 ± 0.250 | -0.55 ± 0.212 |
| Uric acid, Day 4 | 0.17 ± 0.408 | -0.70 ± 0.283 |
| Uric acid, Day 7 | -0.15 ± 0.561 | -0.80 ± 0.707 |
| Uric acid, Day 8 | -0.60 ± 0.970 | -1.05 ± 0.071 |
| Uric acid, Follow-up | -0.53 ± 0.784 | -0.80 ± 0.566 |
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.
| Picomole per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Thyroxine free, Day 2 | -0.018 ± 0.0768 | 0.015 ± 0.0636 |
| Thyroxine free, Day 4 | 0.108 ± 0.1320 | 0.190 ± 0.0283 |
| Thyroxine free, Day 7 | 0.065 ± 0.1011 | 0.120 ± 0.1414 |
| Thyroxine free, Day 8 | 0.117 ± 0.1221 | 0.130 ± 0.0424 |
| Thyroxine free, Follow- up | 0.072 ± 0.1332 | 0.135 ± 0.1485 |
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.
| Nanomoles per liter | GSK2248761 30 mg | Placebo |
|---|---|---|
| Thyroxine total, Day 2 | -0.60 ± 0.648 | -0.40 ± 0.707 |
| Thyroxine total, Day 4 | -0.08 ± 0.979 | 0.50 ± 0.283 |
| Thyroxine total, Day 7 | -0.28 ± 0.773 | 0.10 ± 0.707 |
| Thyroxine total, Day 8 | 0.00 ± 0.874 | 0.00 ± 0.141 |
| Thyroxine total, Follow-up | -0.37 ± 1.019 | 0.05 ± 1.202 |
| Thyroxine binding globulin, Day 2 | -0.33 ± 5.645 | 2.00 ± 2.828 |
| Thyroxine binding globulin, Day 4 | -5.00 ± 3.688 | -6.50 ± 3.536 |
| Thyroxine binding globulin, Day 7 | -0.67 ± 7.005 | -3.00 ± 8.485 |
| Thyroxine binding globulin, Day 8 | 0.17 ± 1.169 | -1.00 ± 2.828 |
| Thyroxine binding globulin, Follow-up | -1.83 ± 2.787 | -1.00 ± 8.485 |
| Total T3, Day 2 | -0.013 ± 0.1334 | 0.170 ± 0.2404 |
| Total T3, Day 4 | 0.068 ± 0.2180 | 0.310 ± 0.2687 |
| Total T3, Day 7 | -0.055 ± 0.1435 | 0.225 ± 0.2333 |
| Total T3, Day 8 | -0.035 ± 0.1252 | 0.190 ± 0.0141 |
| Total T3, Follow-up | -0.005 ± 0.1945 | 0.375 ± 0.1344 |
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.
| Participants | GSK2248761 30 mg | Placebo |
|---|---|---|
| Day 1, Pre-dose, NCS | 3 | 0 |
| Day 1, 4 hour, NCS | 2 | 0 |
| Day 1, 8 hour, NCS | 2 | 0 |
| Day 4, Pre-dose, NCS | 2 | 0 |
| Day 4, 4 hour, NCS | 2 | 0 |
| Day 4, 8 hour, NCS | 3 | 0 |
| Day 7, Pre-dose, NCS | 3 | 0 |
| Day 7, 4 hour, NCS | 3 | 0 |
| Day 7, 8 hour, NCS | 2 | 0 |
| Day 8, Pre-dose, NCS | 3 | 0 |
| Follow-up, NCS | 3 | 0 |
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.
| millimeters of mercury | GSK2248761 30 mg | Placebo |
|---|---|---|
| SBP, Day 1, 4 hour | 4.3 ± 6.35 | -4.5 ± 14.85 |
| SBP, Day 4, Pre-dose | -0.7 ± 5.92 | 0.5 ± 17.68 |
| SBP, Day 4, 4 hour | 3.0 ± 11.70 | 12.5 ± 14.85 |
| SBP, Day 7, Pre-dose | 6.2 ± 6.94 | 6.5 ± 9.19 |
| SBP, Day 7, 4 hour | 9.8 ± 2.71 | 14.5 ± 12.02 |
| SBP, Day 8 | 8.5 ± 7.48 | 13.5 ± 19.09 |
| SBP, Follow-up | 5.8 ± 7.33 | 14.5 ± 6.36 |
| DBP, Day 1, 4 hour | 8.2 ± 8.16 | 1.0 ± 1.41 |
| DBP, Day 4, Pre-dose | 5.8 ± 16.58 | 1.0 ± 15.56 |
| DBP, Day 4, 4 hour | 9.7 ± 10.21 | 3.0 ± 12.73 |
| DBP, Day 7, Pre-dose | 8.2 ± 10.96 | 7.0 ± 7.07 |
| DBP, Day 7, 4 hour | 6.0 ± 9.80 | 8.0 ± 2.83 |
| DBP, Day 8 | 5.2 ± 10.25 | 15.0 ± 9.90 |
| DBP, Follow-up | 4.5 ± 9.07 | 8.0 ± 5.66 |
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.
| Beats per minute | GSK2248761 30 mg | Placebo |
|---|---|---|
| HR , Day 1, 4 hour | -2.5 ± 6.50 | -3.0 ± 4.24 |
| HR, Day 4, Pre-dose | -2.7 ± 6.12 | -6.0 ± 11.31 |
| HR, Day 4, 4 hour | -2.2 ± 3.92 | -6.0 ± 21.21 |
| HR, Day 7, Pre-dose | 3.0 ± 7.54 | -1.0 ± 22.63 |
| HR, Day 7, 4 hour | -0.3 ± 4.63 | -2.5 ± 17.68 |
| HR, Day 8 | 3.7 ± 7.42 | 0.0 ± 12.73 |
| HR, Follow-up | -0.3 ± 5.99 | 5.0 ± 11.31 |
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.
| log 10 copies per milliliter (mL) | GSK2248761 30 mg | Placebo |
|---|---|---|
| Change From Baseline Through Day 8 in Plasma HIV-1 RNA | -0.967 ± 0.3988 | -0.036 ± 0.2495 |
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.
| log10 copies/mL | GSK2248761 30 mg | Placebo |
|---|---|---|
| Change From Baseline to Nadir in Plasma HIV-1 RNA | -1.019 ± 0.3687 | -0.580 ± 0.0157 |
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.
| log10 copies/mL | GSK2248761 30 mg | Placebo |
|---|---|---|
| HIV-1 Rate of Decline by Treatment | -0.1243 (-0.1478 to -0.1008) | 0.0189 (-0.0645 to 0.1023) |
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.
| hours*nanograms (ng)/mL | GSK2248761 30 mg |
|---|---|
| AUC(0-inf) | 2217.73 ± 45 |
| AUC(0-24) | 1842.19 ± 41 |
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.
| ng/mL | GSK2248761 30 mg |
|---|---|
| Cmax | 585.43 ± 39 |
| C24 | 103.40 ± 61 |
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.
| ng/mL | GSK2248761 30 mg |
|---|---|
| C0, Day 7 | 57.47 ± 83 |
| Cτ, Day 7 | 54.27 ± 75 |
| Cmin, Day 7 | 46.37 ± 83 |
| Cmax, Day 7 | 212.93 ± 41 |
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.
| hour | GSK2248761 30 mg |
|---|---|
| tmax | 4.00 (3.0 to 6.0) |
| t1/2 | 7.99 (6.3 to 9.8) |
| tlag | 0.49 (0.0 to 1.0) |
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.
| liter per hour | GSK2248761 30 mg |
|---|---|
| GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F) | 13.53 ± 45 |
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.
| hour*ng/mL | GSK2248761 30 mg |
|---|---|
| GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ) | 9679.71 ± 54 |
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
| hours | GSK2248761 30 mg |
|---|---|
| GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax | 4.01 (3.0 to 6.0) |
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
| hour | GSK2248761 30 mg |
|---|---|
| GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2 | 9.69 ± 25 |
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.
| per cubic millimeter | GSK2248761 30 mg | Placebo |
|---|---|---|
| CD4+ cells, Day 1 | 1.2 ± 76.32 | 76.0 ± 5.66 |
| CD4+ cells, Day 8 | 87.5 ± 58.49 | 102.0 ± 107.48 |
| CD8+ cells, Day 1 | 123.5 ± 348.90 | 526.0 ± 169.71 |
| CD8+ cells, Day 8 | 313.3 ± 218.85 | 531.5 ± 539.52 |
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.
| Percent change | GSK2248761 30 mg | Placebo |
|---|---|---|
| CD4+, Day 1 | -3.2 ± 1.78 | -2.9 ± 1.27 |
| CD4+, Day 8 | -2.4 ± 1.49 | -1.7 ± 0.42 |
| CD8+, Day 1 | -2.8 ± 7.31 | 2.8 ± 3.82 |
| CD8+, Day 8 | -0.4 ± 2.56 | 0.4 ± 1.41 |
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.
| ratio | GSK2248761 30 mg |
|---|---|
| Accumulation Ratio Ro | 1.576 (1.321 to 1.880) |
| Accumulation Ratio R [Cmax] | 1.212 (1.009 to 1.456) |
| Accumulation Ratio R[Ctau] | 1.750 (1.170 to 2.617) |
| Time Invariance Ratio Rs | 1.309 (1.094 to 1.567) |
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.
No measurements were reported for this outcome.
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.
| ng/mL | GSK2248761 30 mg |
|---|---|
| Days 4, 5, 6 and 7 | 0.052 (0.012 to 0.093) |
| Days 5, 6 and 7 | -0.019 (-0.075 to 0.037) |
| Days 6 and 7 | -0.056 (-0.230 to 0.118) |
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.
| hour*ng/mL | GSK2248761 30 mg | IDX899 100 mg | IDX899 200 mg | IDX899 400 mg | IDX899 800 mg |
|---|---|---|---|---|---|
| AUC(0-inf), Day 1 | 2217.73 ± 45 | 9908 ± 21.07 | 23817 ± 46.77 | 33820 ± 58.30 | 37812 ± 81.37 |
| AUC(0-tau), Day 7 | 2903.91 ± 54 | 11650 ± 31.02 | 27209 ± 47.46 | 49649 ± 26.55 | 53683 ± 72.34 |
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.
| ng/mL | GSK2248761 30 mg | IDX899 100 mg | IDX899 200 mg | IDX899 400 mg | IDX899 800 mg |
|---|---|---|---|---|---|
| Cmax, Day 1 | 175.63 ± 39 | 797.8 ± 32.19 | 1686.2 ± 24.67 | 2625.9 ± 34.20 | 3406.4 ± 31.31 |
| Cmax, Day 7 | 212.93 ± 41 | 960.1 ± 22.62 | 2158.9 ± 35.96 | 4140.7 ± 21.54 | 5394.5 ± 46.36 |
| Ctau, Day 1 | 31.02 ± 61 | 128.9 ± 37.36 | 325.6 ± 60.93 | 422.9 ± 81.23 | 364.5 ± 123.77 |
| Ctau, Day 7 | 54.27 ± 75 | 204.7 ± 48.36 | 469.2 ± 63.17 | 864.5 ± 47.44 | 540.3 ± 124.71 |
Collected over Up to 38 Days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| GSK2248761 30 mg | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| Placebo | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Event | GSK2248761 30 mg | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 0/6 | 1/2 |
| NasopharyngitisInfections and infestations | 1/6 | 1/2 |
| HeadacheNervous system disorders | 0/6 | 1/2 |
| PyrexiaGeneral disorders | 0/6 | 1/2 |
| DiarrhoeaGastrointestinal disorders | 2/6 | 0/2 |
| DizzinessNervous system disorders | 1/6 | 0/2 |
| AnxietyPsychiatric disorders | 1/6 | 0/2 |
| HypertensionVascular disorders | 1/6 | 0/2 |
| Age, Continuous(years) | GSK2248761 30 mg | Placebo | Total |
|---|---|---|---|
| Mean | 35.0 ± 7.10 | 28.0 ± 5.66 | 33.3 ± 7.15 |
| Sex: Female, Male(Participants) | GSK2248761 30 mg | Placebo | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 6 | 2 | 8 |
| Race (NIH/OMB)(Participants) | GSK2248761 30 mg | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 5 | 2 | 7 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
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