Phase 3
Completed N=724
A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults
Infection, Human Immunodeficiency Virus · HIV
Source: ClinicalTrials.gov NCT01231516 ↗
Enrolled (actual)
724
Serious AEs
16.6%
Results posted
Jan 2014
Primary outcomePrimary: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 — 71; 64 Percentage of participants — p=0.030
Summary
ING111762 is a 48 week, randomized, double-blind, active-controlled, multicenter, parallel group, non-inferiority study. The study will be conducted in at least 688 HIV-1 infected antiretroviral experienced, integrase-naïve subjects. Subjects will be randomized 1:1 to receive GSK1349572 50 mg once daily or raltegravir (RAL) 400 mg twice daily, each added to an investigator selected background regimen consisting of at least one fully active agent plus no more than one second single agent which may or may not be active. Antiviral activity, safety, pharmacokinetics (PK), and development of viral resistance will be evaluated.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 |
71; 64 | 0.030 sig |
| SECONDARY Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Integrase Inhibitor (INI) Resistance at Time of Protocol Defined Virology Failure (PDVF) |
4; 17 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 |
281; 252 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48 |
307; 287; 278; 257 | — |
| SECONDARY Absolute Values of Cluster of Differentiation 4+ (CD4+) Cell Counts at Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 96 and 144 |
204.5; 193.0; 266.0; 253.0; 280.0; 268.0 | — |
| SECONDARY Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12,16, 24, 32, 40, 48, 96 and 144 |
53.0; 45.0; 60.5; 59.0; 74.0; 75.0 | — |
| SECONDARY Number of Participants With Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions |
32; 25; 16; 14; 12; 8 | — |
| SECONDARY Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities |
36; 9; 11; 3; 4; 0 | — |
| SECONDARY Number of Participants With Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities |
36; 9; 11; 3; 4; 0 | — |
| SECONDARY DTG PK Parameters Including Maximum Plasma Drug Concentration (Cmax), Minimal Plasma Drug Concentration (Cmin), and Average Plasma Pre-dose Concentration (C0_avg) |
0.926; 3.21; 0.849 | — |
| SECONDARY DTG PK Parameter Including Pre-dose Concentration (C0) |
0.786; 0.940; 0.932 | — |
| SECONDARY DTG PK Parameters Including Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau Over a Dosing Interval at Steady State (AUC[0-tau]) |
44.7 | — |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Utility Score |
0.010; 0.019; 0.028; 0.013 | — |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) Thermometer Scores |
6.800; 4.645; 8.894; 5.597 | — |
Eligibility Criteria
Inclusion Criteria
- Antiretroviral therapy (ART)-experienced, Human Immunodeficiency Virus (HIV) -1 infected 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 as documented by HIV-1 RNA >400 copies/mL (c/mL) at Screening and with at least one consecutive HIV-1 RNA >400 c/mL within the four months prior to Screening (unless the Screening HIV-1 RNA is > 1000 c/mL where no additional plasma HIV-1 RNA assessment is needed).
- Have documented resistance (via Screening resistance test) to two or more different classes of antiretroviral agents. For subjects off ART for at least one month, if Screening resistance results provide a fully active agent and do not show two class resistance then historical resistance results from the subject's most recent resistance testing may be used, following consultation with the study virologist and /or medical monitor.
- Integrase inhibitor (INI)-naïve, defined as no prior exposure to any INI (e.g. RAL, elvitegravir, or GSK1349572).
- Able to provide written informed consent prior to Screening.
- French subjects: In France, subjects will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion Criteria
- Screening resistance test result indicates no fully active antiviral agents are available for design of the background regimen.
- Subject-virus does not yield results using genotype/phenotype/tropism at Screening (assay data is essential for eligibility determination).
- Women who are breastfeeding.
- Any evidence of an active AIDS-defining condition (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ 5 times the upper limit of normal (ULN).
- ALT greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin).
Data sourced from ClinicalTrials.gov (NCT01231516). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.