Overview

This trial is active, not recruiting.

Condition infection, human immunodeficiency virus
Treatments gsk1349572, efavirenz
Phase phase 2
Sponsor ViiV Healthcare
Collaborator Shionogi
Start date July 2009
End date February 2010
Trial size 208 participants
Trial identifier NCT00951015, 112276

Summary

This Phase IIb study in HIV-infected antiretroviral naive subjects will select an optimal once daily dose of GSK1349572 from a range of doses for future evaluation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
subjects will receive GSK1349572 10mg once daily blinded to dose
gsk1349572
investigational HIV-1 integrase inhibitor
(Experimental)
subjects will receive GSK1349572 25mg once daily blinded to dose
gsk1349572
investigational HIV-1 integrase inhibitor
(Experimental)
subjects will receive GSK1349572 50mg once daily blinded to dose
gsk1349572
investigational HIV-1 integrase inhibitor
(Other)
efavirenz will serve as the internal control arm
efavirenz
approved therapy for HIV-1 infection, used as an internal study control

Primary Outcomes

Measure
Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16
time frame: Week 16

Secondary Outcomes

Measure
Viral Change Over the Initial 2 Weeks of Treatment
time frame: Baseline and Week 2
Change From Baseline in HIV-1 RNA at the Indicated Time Points
time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points
time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Number of Participants With New HIV-associated Conditions of the Indicated Class
time frame: From Baseline up to Week 96
Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)
time frame: From Baseline up to Week 96
Number of Participants With Plasma HIV-1 RNA <50 c/mL
time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Number of Participants With Plasma HIV-1 RNA <400 c/mL
time frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)
time frame: From Baseline up to Week 96/Early Withdrawal
Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities
time frame: From Baseline up to Week 96/Early Withdrawal
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
time frame: From Baseline up to Week 96/Early Withdrawal
Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
time frame: From Baseline up to Week 96/Early Withdrawal
Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
time frame: From Baseline up to Week 96/Early Withdrawal
Plasma DTG Concentration
time frame: Week 2, Week 12, and Week 24
AUC(0-tau) of DTG
time frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
Cmax, Cmin, and Ctau of DTG
time frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
C0 and C0 Avg of DTG
time frame: Week 2, Week 12, and Week 24
Time to Maximal Drug Concentration (Tmax) of DTG
time frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
time frame: Week 2
Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters
time frame: Week 96
Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
time frame: Week 96
Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters
time frame: Week 96

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - HIV-1 infected male or female adults at least 18 years of age. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol); - HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL; - CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines dictate); - ART-naive (less than or equal to 10 days of prior therapy with any antiretroviral agent). Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will be exclusionary. - No evidence of viral resistance to any antiretroviral drug indicative of primary transmitted resistance at screening; - Able to understand and comply with protocol requirements; - Able to provide written informed consent prior to screening; - French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Note: Subjects starting abacavir as part of the NRTI backbone must have been screened and be negative for the HLA-B*5701 allele. Exclusion Criteria: - Any pre-existing or serious mental or physical disorder which could compromise ability to comply with the protocol or compromise subject safety; - Women who are pregnant or breastfeeding; - An active AIDS-defining condition at the screening visit; - Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives; - History of clinically relevant pancreatitis or hepatitis within the previous 6 months, including HBsAg positive result. Asymptomatic HCV infection will not be exclusionary, however subject who will require HCV therapy during the trial should be excluded. Any subject with a history of liver cirrhosis with or without hepatitis viral co-infection will be excluded. - Any condition which could interfere with the absorption, distribution, metabolism or excretion of the drug; - Any acute or Grade 4 laboratory abnormality at screening; - History of upper gastrointestinal bleed and/or subjects with active peptic ulcer disease; - Estimated creatinine clearance <50 mL/min; - Alanine aminotransferase (ALT) greater than or equal to 5 times ULN; - Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin); - Lipase greater than or equal to 3xULN; - Hemoglobin < 100 g/L(10 g/dL); - History of allergy to the study drugs or their components or drugs of their class; - Treatment with radiation therapy, cytotoxic chemotherapeutic agents, any agents with activity against HIV-1 or immunomodulators within 28 days prior to screening; - Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening; - History of protocol-defined cardiac diseases; - Personal or family history of prolonged QT syndrome; - Any clinically significant finding, as specified in the protocol, on electrocardiograph (ECG); - Significant blood loss in excess of 500 mL within a 56 day period prior to screening visit; - Immunization within 30 days prior to first dose of investigational product; - French subjects: The subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.

Additional Information

Official title A Phase IIb Study to Select a Once Daily Dose of GSK1349572 Administered With Either Abacavir/Lamivudine or Tenofovir/Emtricitabine in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
Description This Phase IIb study in HIV-infected antiretroviral naive adult subjects will include a dose-ranging evaluation of GSK1349572 10mg, 25mg and 50mg once daily blinded doses and a control arm of open label efavirenz 600mg once daily. Background ART for all study subjects will be chosen by the investigators and will be either Truvada or Epzicom/Kivexa. Data from the three doses of GSK1349572 will be compared on the basis of antiviral activity, safety/tolerability and pharmacokinetics over 16-24 weeks. Several planned interim analyses will evaluate data in real time; any doses considered inferior will be dropped and subjects on those doses of GSK1349572 will have the option to switch to either the highest dose still under investigation or the selected dose. Subjects will be able to remain in the study, unless they reach a stopping criterion, for at least 96 weeks. ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by ViiV Healthcare.