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Safety and Tolerability Study to Evaluate Lower Dose of GSK2248761 in Antiretroviral Treatment-Naive HIV-1 Infected Adults.

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ClinicalTrials.gov Identifier: NCT00945282
Recruitment Status : Completed
First Posted : July 24, 2009
Results First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

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.


Condition or disease Intervention/treatment Phase
Infection, Human Immunodeficiency Virus Drug: GSK2248761 Drug: Lopinavir/ritonavir Drug: HAART Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Proof of Concept Study for GSK2248761 (An Extension of NV-05A-002: A Phase I/IIa Double-Blind Study to Evaluate the Safety and Tolerability, Antiretroviral Activity, Pharmacokinetics and Pharmacodynamics of IDX12899 in Antiretroviral Treatment-Naive HIV-1 Infected Subjects, Completed by Idenix)
Actual Study Start Date : October 20, 2009
Actual Primary Completion Date : November 28, 2009
Actual Study Completion Date : November 28, 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Lopinavir

Arm Intervention/treatment
Experimental: Cohort 1
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
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.

Drug: Lopinavir/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.
Other Name: Kaletra

Drug: HAART
Highly Active Antiretroviral therapy of the doctor's choice.

Drug: Placebo
Placebo is a capsule with no drug in it.

Experimental: Cohort 2
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
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.
Other Name: Kaletra

Drug: HAART
Highly Active Antiretroviral therapy of the doctor's choice.

Drug: Placebo
Placebo is a capsule with no drug in it.

Drug: GSK2248761
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.




Primary Outcome Measures :
  1. Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) [ Time Frame: 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.

  2. Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count [ Time Frame: 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.

  3. Change From Baseline in Hematology Paramaters- Hemoglobin [ Time Frame: 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.

  4. Change From Baseline in Hematology Paramaters- Platelet Count [ Time Frame: 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.

  5. Change From Baseline in Hematology Paramaters- Red Blood Cell Count [ Time Frame: 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.

  6. Change From Baseline in Hematology Parameters- Total Neutrophil [ Time Frame: 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.

  7. Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH) [ Time Frame: 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.

  8. Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV) [ Time Frame: 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.

  9. Change From Baseline in Hematology Paramaters- Hematocrit [ Time Frame: 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.

  10. Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration [ Time Frame: 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.

  11. Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein [ Time Frame: 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.

  12. Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin. [ Time Frame: 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.

  13. Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase [ Time Frame: 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.

  14. Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate [ Time Frame: 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.

  15. Change From Baseline in Clinical Chemistry Paramaters- Phosphorus [ Time Frame: 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.

  16. Change From Baseline in Clinical Chemistry Paramaters- Uric Acid [ Time Frame: 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.

  17. Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free [ Time Frame: 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.

  18. Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3. [ Time Frame: 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.

  19. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [ Time Frame: 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.

  20. Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: 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.

  21. Change From Baseline in HR [ 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) ]
    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.

  22. Change From Baseline Through Day 8 in Plasma HIV-1 RNA [ Time Frame: 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.

  23. Change From Baseline to Nadir in Plasma HIV-1 RNA [ Time Frame: 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.

  24. HIV-1 Rate of Decline by Treatment [ Time Frame: 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.

  25. 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]) [ Time Frame: 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.

  26. GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) [ Time Frame: 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.

  27. 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 [ Time Frame: 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.

  28. GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag) [ Time Frame: 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.

  29. GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F) [ Time Frame: 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.

  30. GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ) [ Time Frame: 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.

  31. GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax [ Time Frame: 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

  32. GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2 [ Time Frame: 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

  33. Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8. [ Time Frame: 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.


Secondary Outcome Measures :
  1. Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8 [ Time Frame: 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.

  2. Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration [ 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 ]
    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.

  3. Change From Baseline in Reverse Transcriptase Sequences of HIV-1 at Day 8 [ Time Frame: 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.

  4. Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7 [ 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 ]
    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.

  5. PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality [ 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 ]
    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.

  6. PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality [ 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 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination): Exclusion Criteria for Screening ECG: Heart rate: (males) <45 and >100 bpm (females) <50 and >100 bpm, QRS duration: >120 msec, QTc interval (Bazett): > 450 msec. Non-sustained (>= 3 consecutive beats) or sustained ventricular tachycardia. Sinus Pauses >2.5 seconds. 2nd degree (Type II) or higher AV block. Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization)).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00945282


Locations
Argentina
GSK Investigational Site
Buenos Aires, Argentina, B1602DBG
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare

Publications:
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00945282     History of Changes
Other Study ID Numbers: 113020
First Posted: July 24, 2009    Key Record Dates
Results First Posted: November 29, 2018
Last Update Posted: November 29, 2018
Last Verified: August 2017

Keywords provided by ViiV Healthcare:
IDX12899
adaptive
monotherapy
pharmacokinetics
Treatment-naive
HIV-1
GSK2248761
NNRTI
HIV Infections
treatment naive

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
Anti-Retroviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors