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Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine

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ClinicalTrials.gov Identifier: NCT01641809
Recruitment Status : Completed
First Posted : July 17, 2012
Results First Posted : January 30, 2020
Last Update Posted : January 30, 2020
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:

The study is designed to select a dose of GSK1265744 primarily on the basis of antiviral activity and tolerability in HIV-1 infected, antiretroviral naive subjects.

This study consists of two parts:

Induction Phase: Approximately 200 subjects will be randomized (50 subjects in each of the 4 treatment arms). The Induction Phase consists of a 24 week dose-ranging evaluation of GSK1265744 at blinded doses of 10 mg, 30 mg and 60 mg once-daily and a control arm of open-label efavirenz (EFV) 600 mg once daily. The background dual nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy (ART) for all arms will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) as selected by the Investigator. Subjects randomized to a GSK1265744 containing arm, who successfully complete 24 weeks on study and demonstrate virologic suppression (defined as having a plasma HIV-1 ribonucleic acid [RNA] <50 copies per milliliter [c/mL] before Week 24, with no signs of virologic rebound) will become eligible for the Maintenance Phase of this study.

Maintenance Phase: The background NRTIs will be discontinued and the subjects will continue their randomized dose of GSK1265744 in combination with rilpivirine (RPV) 25 mg once-daily for an additional 72 weeks. The Maintenance phase will evaluate the ability of this two drug ART regimen to maintain virologic suppression through Week 48, Week 72 and Week 96. Subjects randomized to the EFV arm will continue on their randomized regimen through Week 96.

After completion of the maintenance phase, subjects could enroll in the Open-Label Phase to continue GSK1265744 + RPV treatment as long as they continue to derive clinical benefit and until it is locally approved and commercially available.


Condition or disease Intervention/treatment Phase
Infection, Human Immunodeficiency Virus HIV Infections Drug: GSK1265744 10 mg Drug: GSK1265744 30 mg Drug: GSK1265744 60 mg Drug: Efavirenz 600 mg Drug: Rilpivirine 25 mg Drug: Placebo Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC) Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb, Dose Ranging Study of Oral GSK1265744 in Combination With Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus -1 (HIV-1) Virologic Suppression Followed by an Evaluation of Maintenance of Virologic Suppression When Oral GSK1265744 is Combined With Oral Rilpivirine in HIV-1 Infected, Antiretroviral Therapy Naive Adult Subjects
Actual Study Start Date : August 6, 2012
Actual Primary Completion Date : October 10, 2013
Actual Study Completion Date : January 15, 2019

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Arm 1 GSK1265744 10 mg
In the Induction Phase subjects will receive oral tablets of GSK1265744 10 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 10 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.
Drug: GSK1265744 10 mg
GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Drug: Rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Drug: Placebo
Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Experimental: Arm 2 GSK1265744 30 mg
In the Induction Phase subjects will receive oral tablets of GSK1265744 30 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 30 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.
Drug: GSK1265744 30 mg
GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Drug: Rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Drug: Placebo
Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Experimental: Arm 3 GSK1265744 60 mg
In the Induction Phase subjects will receive oral tablets of GSK1265744 60 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 60 mg + Rilpivirine 25 mg once daily from Week 24 to Week 96.
Drug: GSK1265744 60 mg
GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Drug: Rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Active Comparator: Arm 4 Efavirenz 600 mg
In the Induction Phase and Maintenance Phase subjects will receive oral tablets of Efavirenz 600 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine).
Drug: Efavirenz 600 mg
Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.




Primary Outcome Measures :
  1. Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (mL) at Week 48 Using the Missing, Switch, Discontinuation Equals Failure (MSDF) Algorithm [ Time Frame: Week 48 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was determined using the MSDF algorithm based on the current US Food and Drug Administration (FDA) definition of Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to visit window) as well as participants who switch their concomitant antiretroviral therapy prior to the visit of interest as non-responders. Virological response within an analysis window was determined by the last available HIV-1 RNA measurement in that window while the participant was on-treatment. MSDF response rate was calculated as number of responders in the analysis window divided by the number of participants in the analysis population. ITT-E Population comprised of all randomized participants who received at least one dose of investigational product.


Secondary Outcome Measures :
  1. Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL Until Week 96 Using the MSDF Algorithm [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. The percentage of participants with HIV-1 RNA <400 copies/mL over time was determined using the MSDF algorithm based on the current US FDA definition of the Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to visit window) as well as participants who switch their concomitant antiretroviral therapy prior to the visit of interest as non-responders. Virological response within an analysis window was determined by the last available HIV-1 RNA measurement in that window while the participant was on-treatment. MSDF response rate was calculated as number of responders in the analysis window divided by the number of participants in the analysis population.

  2. Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL Until Week 96 Using the Observed Case Analysis [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with HIV-1 RNA <400 copies/mL over time was determined using the observed case analysis, which did not impute for any missing assessments. Observed case response rate was calculated as the number of participants with a positive response at the time point where the participant is on randomized therapy divided by the number of participants in the analysis population with an assessment in the scheduled visit window during the randomized period.

  3. Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL Over Time by Visit Using the MSDF Algorithm [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300 and 312 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with HIV-1 RNA <50 copies/mL over time was determined using the MSDF algorithm based on the current US FDA definition of the Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to visit window) as well as participants who switch their concomitant antiretroviral therapy prior to the visit of interest as non-responders. Virological response within an analysis window was determined by the last available HIV-1 RNA measurement in that window while the participant was on-treatment. MSDF response rate was calculated as number of responders in the analysis window divided by the number of participants in the analysis population.

  4. Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL Over Time by Visit Using Observed Case Analysis [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with HIV-1 RNA <50 copies/mL over time was determined using the observed case analysis, which did not impute for any missing assessments. Observed case response rate was calculated as the number of participants with a positive response at the time point where the participant is on therapy divided by the number of participants in the analysis population with an assessment in the scheduled visit window during the randomized period or open-label phase.

  5. Absolute Values for Plasma Logarithm to the Base 10 (log10) HIV-1 RNA Over Time by Visit [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Plasma samples for quantitative analysis of HIV-1 RNA were collected at indicated time points. Baseline value is the last pre-treatment value observed.

  6. Change From Baseline in Plasma log10 HIV-1 RNA Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Plasma samples for quantitative analysis of HIV-1 RNA were collected at indicated time points. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  7. Number of Participants With Post-Baseline HIV-1 Associated Conditions Progression of Disease [ Time Frame: Up to Week 324 ]
    HIV-1 associated conditions were assessed according to the 1993 Centers for Disease Control and Prevention (CDC) Revised Classification System for HIV Infection in Adults. The clinical categories of HIV infection as per CDC system are class A=Asymptomatic HIV infection or lymphadenopathy or acute HIV infection; class B=symptomatic non-acquired immunodeficiency syndrome (AIDS) conditions and class C=AIDS indicator conditions. Number of participants experiencing disease progression is presented, where disease progression is defined as the progression from Baseline HIV disease status as follows: CDC class A at Baseline to CDC class C event; CDC Class B at Baseline to CDC Class C event; CDC Class C at Baseline to new CDC Class C event; and CDC class A, B or C at Baseline to death.

  8. Absolute Values for Cluster of Differentiation 4+ (CD4+) Cell Count During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    CD4+ cell counts were assessed by flow cytometry. Baseline value is the last pre-treatment value observed.

  9. Change From Baseline in CD4+ Cell Count Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    CD4+ cell counts were assessed by flow cytometry. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  10. Number of Participants With Treatment Emergent Phenotypic Resistance [ Time Frame: Up to Week 324 ]
    Plasma samples were collected for drug resistance testing. Phenotypic resistance data for the following drugs under integrase inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), NRTI and proteasome inhibitor drug classes is presented for participants with confirmed virologic failure: GSK1265744, Raltegravir [RAL], Delavirdine [DLV], Efavirenz [EFV], Etravirine [ETR], Nevirapine (NVP), RPV, 3TC, ABC, FTC, TDF, Zidovudine [ZDV], Stavudine [d4T], Didanosine [ddI], Atazanavir/ritonavir [ATV/r], Darunavir (DRV)/r, Fosamprenavir/r [FPV/r], Indinavir/r [IDV/r], Lopinavir/r [LPV/r], Nelfinavir [NFV], Ritonavir [RTV], Saquinavir/r [SQV/r], Tipranavir/r [TPV/r]. On-treatment Phenotypic Resistance population comprised of all participants in the ITT-E Population with available on-treatment phenotypic resistance data, excluding participants who are not protocol-defined virologic failures.

  11. Number of Participants With Treatment Emergent Genotypic Mutations Associated With Development of Resistance [ Time Frame: Up to Week 324 ]
    Plasma samples were collected for drug resistance testing. The treatment emergent INI mutations associated with development of resistance to RAL, ELV, dolutegravir (DTG) or GSK1265744 and major resistance mutations to other classes (NRTI, NNRTI, PI) as defined by International AIDS society (IAS)-United States of America (USA) are presented. On-treatment Genotypic Resistance population comprised of all participants in the ITT-E Population with available on-treatment genotypic resistance data, excluding participants who are not protocol-defined virologic failures.

  12. Number of Participants With Adherence to Study Treatment [ Time Frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300 and 312 ]
    Number of participants with >=90% adherence to study treatment based on pill count is summarized.

  13. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 16 and Week 24 Using MSDF Algorithm-Induction Phase [ Time Frame: Week 16 and Week 24 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with HIV-1 RNA <50 copies/mL over time was determined using the MSDF algorithm based on the current US FDA definition of the Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to visit window) as well as participants who switch their concomitant antiretroviral therapy prior to the visit of interest as non-responders. Virological response within an analysis window was determined by the last available HIV-1 RNA measurement in that window while the participant was on-treatment. MSDF response rate was calculated as number of responders in the analysis window divided by the number of participants in the analysis population.

  14. Percentage of Participants With HIV-1 RNA <50 Copies/mL From Week 24 Through Week 96 by Visit Using MSDF Algorithm-Maintenance Phase [ Time Frame: Weeks 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. The end point was determined using MSDF algorithm based on the current US FDA definition of Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to visit window) as well as participants who switch their concomitant antiretroviral therapy prior to the visit of interest as non-responders. Virological response within an analysis window was determined by the last available HIV-1 RNA measurement in that window while the participant was on-treatment. MSDF response rate was calculated as number of responders in the analysis window divided by the number of participants in the analysis population. ITT-Maintenance Exposed (ME) Population comprised of all participants randomized to GSK1265744 and who received at least one dose of investigational product during maintenance phase of the study.

  15. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Maintenance Phase [ Time Frame: Week 24 to Week 96 ]
    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 SAE is 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; is a congenital anomaly/birth defect; other medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcomes mentioned before; all events of possible drug-induced liver injury with hyperbilirubinemia. Maintenance Safety Population comprised of all participants randomized to GSK1265744 and who were exposed to investigational products during the maintenance phase of the study with the exception of any participants with documented evidence of not having consumed any amount of investigational product.

  16. Number of Participants With Maximum Treatment-emergent Clinical Chemistry Toxicities-Maintenance Phase [ Time Frame: Week 24 to Week 96 ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotranferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), carbon dioxide(CO2)/bicarbonate, cholesterol, creatine kinase (CK), creatinine, glucose, low density lipoprotein (LDL) cholesterol, lipase, inorganic phosphorus, potassium, sodium, total bilirubin and triglycerides. A toxicity is considered treatment emergent if it developed or increased in intensity from Baseline while on-treatment. Laboratory toxicities were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  17. Number of Participants With Maximum Treatment-emergent Hematology Toxicities-Maintenance Phase [ Time Frame: Week 24 to Week 96 ]
    Blood samples were collected for the analysis of following hematology parameters: Activated Partial Thromboplastin Time (APTT), hemoglobin, international normalized ratio (INR), platelet count, prothrombin time (PT), total neutrophils and white blood cell (WBC) count. A toxicity is considered treatment emergent if it developed or increased in intensity from Baseline while on-treatment. Laboratory toxicities were graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  18. Number of Participants With AEs and SAEs Over Time [ Time Frame: Up to Week 324 ]
    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 SAE is 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; is a congenital anomaly/birth defect; other medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcomes mentioned before; all events of possible drug-induced liver injury with hyperbilirubinemia. Safety Population comprised of all randomized participants who were exposed to investigational products with the exception of any participants with documented evidence of not having consumed any amount of investigational product.

  19. Number of Participants With Maximum Treatment-emergent Clinical Chemistry Toxicities Over Time [ Time Frame: Up to Week 324 ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: ALT, albumin, ALP, AST, CO2/bicarbonate, cholesterol, CK, creatinine, glucose, LDL cholesterol, lipase, inorganic phosphorus, potassium, sodium, total bilirubin and triglycerides. Laboratory toxicities were graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  20. Number of Participants With Maximum Treatment-emergent Hematology Toxicities Over Time [ Time Frame: Up to Week 324 ]
    Blood samples were collected for the analysis of following hematology parameters: APTT, hemoglobin, INR, platelet count, PT, total neutrophils and WBC count. Laboratory toxicities were graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  21. Absolute Values for ALT, AST, CK During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Blood samples were collected for the analysis of ALT, AST and CK. Baseline value is the last pre-treatment value observed.

  22. Absolute Values for Creatinine and Total Bilirubin During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Blood samples were collected for the analysis of creatinine and total bilirubin (T. bilirubin). Baseline value is the last pre-treatment value observed.

  23. Absolute Values for Estimated Creatinine Clearance During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 16, 20, 24, 26, 40, 48, 60 and 96 ]
    Blood samples were collected for the analysis of estimated creatinine clearance. Estimated creatinine clearance was calculated using Cockcroft-Gault formula. Baseline value is the last pre-treatment value observed.

  24. Absolute Values for Hemoglobin During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Blood samples were collected for the analysis of hemoglobin level. Baseline value is the last pre-treatment value observed.

  25. Absolute Values for Platelet Count, Total Neutrophils and WBC Count During Double-blind Randomized Treatment Until Week 96 [ Time Frame: Baseline (Day 1), Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84 and 96 ]
    Blood samples were collected for the analysis of platelet count, total neutrophils (T. neutrophils) and WBC count. Baseline value is the last pre-treatment value observed.

  26. Change From Baseline in ALT, AST and CK Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Blood samples were collected for the analysis of ALT, AST and CK. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  27. Change From Baseline in Creatinine and Total Bilirubin Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Blood samples were collected for the analysis of creatinine and total bilirubin. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  28. Change From Baseline in Estimated Creatinine Clearance Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 16, 20, 24, 26, 40, 48, 60, 96, 180, 204, 252 and 264 ]
    Blood samples were collected for the analysis of estimated creatinine clearance. Estimated creatinine clearance was calculated using Cockcroft-Gault formula. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  29. Change From Baseline in Hemoglobin Level Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Blood samples were collected for the analysis of hemoglobin level. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  30. Change From Baseline in Total Neutrophils, Platelet Count and WBC Count Over Time by Visit [ Time Frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312 and 324 ]
    Blood samples were collected for the analysis of total neutrophils, platelet count and WBC count. Baseline value is the last pre-treatment value observed. Change from Baseline is calculated as value at indicated time point minus Baseline value.

  31. Percentage of Participants Who Discontinued Investigational Product Due to Adverse Events [ Time Frame: Up to Week 324 ]
    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. The percentage of participants with adverse events leading to withdrawal/permanent discontinuation of investigational product is presented.

  32. Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Up to Week 324 ]
    Twelve lead ECG was performed after the participants had rested in a semi-supine position for at least 5 minutes using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst case results at any time on-treatment is presented.

  33. Number of Participants With AEs and SAEs-Induction Phase [ Time Frame: Up to Week 24 ]
    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 SAE is 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; is a congenital anomaly/birth defect; other medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcomes mentioned before; all events of possible drug-induced liver injury with hyperbilirubinemia.

  34. Number of Participants With Maximum Treatment-emergent Clinical Chemistry Toxicity-Induction Phase [ Time Frame: Up to Week 24 ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: ALT, albumin, ALP, AST, CO2/bicarbonate, chloride, cholesterol, CK, creatinine, glucose, high density lipoprotein (HDL) cholesterol, LDL cholesterol, lipase, inorganic phosphorus, potassium, sodium, total bilirubin, triglycerides and urea/blood urea nitrogen (BUN). A toxicity was considered treatment emergent if it developed or increased in intensity from Baseline while on-treatment. Laboratory toxicities were graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  35. Number of Participants With Maximum Treatment-emergent Hematology Toxicities-Induction Phase [ Time Frame: Up to Week 24 ]
    Blood samples were collected for the analysis of following hematology parameters: APTT, basophils, eosinophils, hematocrit, hemoglobin, INR, lymphocytes, mean corpuscle volume (MCV), monocytes, platelet count, PT, red blood cell (RBC) count, total neutrophils and WBC count. A toxicity was considered treatment emergent if it developed or increased in intensity from Baseline while on-treatment. Laboratory toxicities were graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, where Grade 1=Mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening.

  36. Percentage of Participants Who Discontinued Treatment Due to Adverse Events-Induction Phase [ Time Frame: Up to Week 24 ]
    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. The percentage of participants with adverse events leading to withdrawal/permanent discontinuation of investigational product is presented.

  37. Percentage of Participants Who Discontinued Treatment Due to Adverse Events-Maintenance Phase [ Time Frame: Week 24 to Week 96 ]
    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. The percentage of participants with adverse events leading to withdrawal/permanent discontinuation of investigational product is presented.

  38. Area Under the Concentration Time Curve Over the Dosing Interval (AUC[0-tau]) for GSK1265744 at Week 2 [ Time Frame: pre-dose, 1, 2, 3, 4, 8 and 24 hours post-dose at Week 2 ]
    Blood samples for pharmacokinetic (PK) analysis were collected at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. The PK Summary Population comprised of all participants who received GSK1265744 or with Rilpivirine, underwent intensive and/or limited/sparse PK sampling during the study, and provided evaluable GSK1265744 and Rilpivirine plasma concentration data

  39. Maximum Observed Concentration (Cmax) for GSK1265744 at Week 2 [ Time Frame: pre-dose, 1, 2, 3, 4, 8 and 24 hours post-dose at Week 2 ]
    Blood samples for PK analysis were collected at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

  40. Concentration at the End of a Dosing Interval (Ctau) for GSK1265744 at Week 2 [ Time Frame: pre-dose, 1, 2, 3, 4, 8 and 24 hours post dose at Week 2 ]
    Blood samples for PK analysis were collected at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

  41. AUC(0 to Tau) for Rilpivirine [ Time Frame: pre-dose and 2 to 4 hours post-dose at Weeks 26 and 36 ]
    Data was not collected for analysis of rilpivirine PK parameters.

  42. Cmax for Rilpivirine [ Time Frame: pre-dose and 2 to 4 hours post-dose at Weeks 26 and 36 ]
    Data was not collected for analysis of rilpivirine PK parameters.

  43. Ctau for Rilpivirine [ Time Frame: pre-dose and 2 to 4 hours post-dose at Weeks 26 and 36 ]
    Data was not collected for analysis of rilpivirine PK parameters.



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected male or female subjects >= 18 years of age
  • Screening plasma HIV-1 RNA >=1000 c/mL
  • CD4+ cell count >=200 cells/millimeter (mm)^3
  • ART-naive defined as having =<10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
  • Female subjects of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy during the study

Exclusion Criteria:

  • Any evidence at screening of an active Centers for Disease and Prevention Control (CDC) Category C disease
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
  • History of ongoing or clinically relevant hepatitis within the previous 6 months, and subjects with moderate to severe hepatic impairment will be excluded
  • Women who are breastfeeding
  • Subject, who in the investigator's judgment, poses a significant suicide risk
  • Any clinically significant finding on screening or baseline electrocardiograph (ECG)
  • The presence of any specific laboratory abnormalities at Screening
  • History of cardiac disease
  • Clinically relevant pancreatitis
  • Subjects who are unlikely to complete the dosing schedule due to a pre-existing physical or mental condition
  • Any condition which impairs the absorption, distribution, metabolism or excretion of the investigational product
  • Any evidence of primary resistance based upon the presence of a major resistance associated mutation in the Screening HIV genotype, or any historical genotype
  • Treatment with any protocol-specified excluded medication

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): NCT01641809


Locations
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United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35294
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85015
United States, Arkansas
GSK Investigational Site
Little Rock, Arkansas, United States, 72207
United States, California
GSK Investigational Site
Bakersfield, California, United States, 93301
GSK Investigational Site
Beverly Hills, California, United States, 90211
GSK Investigational Site
Long Beach, California, United States, 90813
GSK Investigational Site
Los Angeles, California, United States, 90069
GSK Investigational Site
San Francisco, California, United States, 94115
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80209
United States, District of Columbia
GSK Investigational Site
Washington, District of Columbia, United States, 20007
GSK Investigational Site
Washington, District of Columbia, United States, 20037
United States, Florida
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33316
GSK Investigational Site
Fort Pierce, Florida, United States, 34982
GSK Investigational Site
Miami, Florida, United States, 33137
GSK Investigational Site
Oakland Park, Florida, United States, 33309
GSK Investigational Site
Orlando, Florida, United States, 32803
GSK Investigational Site
West Palm Beach, Florida, United States, 33407
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30339
GSK Investigational Site
Augusta, Georgia, United States, 30912
GSK Investigational Site
Macon, Georgia, United States, 31201
GSK Investigational Site
Savannah, Georgia, United States, 31401
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02111
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55415
United States, Missouri
GSK Investigational Site
Kansas City, Missouri, United States, 64111
United States, Nebraska
GSK Investigational Site
Omaha, Nebraska, United States, 68198
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89106
United States, New Jersey
GSK Investigational Site
Hillsborough, New Jersey, United States, 08844
GSK Investigational Site
Neptune, New Jersey, United States, 07753
United States, New York
GSK Investigational Site
Albany, New York, United States, 12209
GSK Investigational Site
Buffalo, New York, United States, 14201
GSK Investigational Site
New York, New York, United States, 10065
GSK Investigational Site
Valhalla, New York, United States, 10595
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 02906
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29425
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78751
GSK Investigational Site
Dallas, Texas, United States, 75246
United States, Virginia
GSK Investigational Site
Annandale, Virginia, United States, 22003
Canada, British Columbia
GSK Investigational Site
Vancouver, British Columbia, Canada, V6Z 2C7
GSK Investigational Site
Vancouver, British Columbia, Canada, V6Z 2T1
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M4N 3M5
GSK Investigational Site
Toronto, Ontario, Canada, M4T 3A7
GSK Investigational Site
Toronto, Ontario, Canada, M5G 1K2
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4E9
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4P9
GSK Investigational Site
Montreal, Quebec, Canada, H3A 1T1
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01641809    
Other Study ID Numbers: 116482
First Posted: July 17, 2012    Key Record Dates
Results First Posted: January 30, 2020
Last Update Posted: January 30, 2020
Last Verified: January 2020
Keywords provided by ViiV Healthcare:
HIV -1
GSK1265744
maintenance phase
dose selection
Additional relevant MeSH terms:
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Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Virus Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Tenofovir
Lamivudine
Emtricitabine
Efavirenz
Abacavir
Rilpivirine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors