Phase 2
Completed N=51
A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir
Infection, Human Immunodeficiency Virus
Source: ClinicalTrials.gov NCT00950859 ↗
Enrolled (actual)
51
Serious AEs
41.2%
Results posted
Oct 2013
Primary outcomePrimary: Number of Participants Who Achieved HIV-1 RNA <400 Copies (c)/Milliliter (mL) or at Least 0.7 log10 c/mL Below Their Baseline Value at Day 11 — 21; 23 Participants
Summary
Integrase is an enzyme produced by HIV so that the virus can multiply in the human body. GSK1349572 is a new drug in the integrase inhibitor class that prevents the enzyme from working properly and therefore prevents the virus from multiplying.
GSK1349572 has shown to be effective against viruses in a short-term monotherapy study in adults with no previous exposure to integrase inhibitors. The purpose of this study is to determine whether GSK1349572 is effective in the treatment of HIV-infected patients who no longer respond to treatment with the approved integrase inhibitor raltegravir and carry viruses with resistance to this drug. The safety and efficacy of GSK1349572 50mg once daily in combination with the background HIV drugs previously administered (unless discontinuation of a particular drug is required) will be assessed over 10 days (functional monotherapy phase), followed by the evaluation of the safety and efficacy of GSK1349572 given with a new optimised background regimen from Day 11 through at least Week 24.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Achieved HIV-1 RNA <400 Copies (c)/Milliliter (mL) or at Least 0.7 log10 c/mL Below Their Baseline Value at Day 11 |
21; 23 | — |
| SECONDARY Mean Change From Baseline in Plasma HIV-1 RNA at Day 6 to 8, Day 11, Weeks 4, 12, 24, 48, 72, 96, From Week 108 Every 12 Weeks up to Study Completion |
-1.31; -1.40; -1.45; -1.76; -1.82; -2.06 | — |
| SECONDARY Number of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL at Baseline and Weeks 4, 12, 24, 48, 72, and 96: TLOVR Analysis. |
0; 0; 9; 12; 13; 16 | — |
| SECONDARY Proportion of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL From Week 48 Every 12 Weeks up to Study Completion |
60; 80; 69; 94; 64; 78 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Day 11 and Weeks 4, 12, 24, 48, 72, 96, Week 108 Every 12 Weeks up to Study Completion |
114; 202; 34; 14; 57; 35 | — |
| SECONDARY Cmax, Cmin, and Ctau of DTG |
3.04; 5.41; 0.69; 2.72; 0.48; 2.61 | — |
| SECONDARY C0 Assessment of DTG |
0.51; 3.20; 0.57; 2.55; 0.38; 2.38 | — |
| SECONDARY Tmax of DTG |
2.97; 2.00 | — |
| SECONDARY AUC0-24 Assessment of DTG |
36.46; 93.36 | — |
| SECONDARY Number of Participants With the Indicated HIV-1 Associated Conditions, Excluding Recurrences |
3; 2; 2; 0; 2; 0 | — |
| SECONDARY Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shifts to CDC Class C or Death |
0; 2; 0; 2; 1; 0 | — |
| SECONDARY Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion |
6; 1; 7; 3; 9; 3 | — |
| SECONDARY Number of Participants With the Indicated Genotypic Resistance at Baseline |
3; 2; 4; 8; 2; 1 | — |
| SECONDARY Median Fold Change in Sensitivity to DTG by the Baseline (Day 1) IN Mutational Group |
21; 4; 5.5; 5.5; 7.8; 9.48 | — |
| SECONDARY 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 |
11; 5; 0; 1; 3; 4 | — |
| SECONDARY Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance |
3; 0; 4; 2; 1; 0 | — |
| SECONDARY Number of Participants With the Indicated Grade 3 and Grade 4 Clinical Chemistry Toxicities |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Grade 3 and Grade 4 Hematological Toxicities |
0; 1; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- HIV-1 infected male or female adults at least 18 years of age with a plasma HIV-1 RNA > 1,000 copies/mL at study entry. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
- ART-experienced (defined as on stable ART for at least the last 2 months) and is either currently experiencing virologic failure to RAL or experienced virologic failure to RAL > 8 weeks prior to Screening
- Must have documented RAL genotypic resistance on study entry genotype
- Must have documented genotypic or phenotypic resistance to at least one drug from each of three or more of all approved classes of ART
- For Cohort II, Subjects MUST be able to receive at least one fully active drug as part of the Day 11 optimised background regimen
- Willing and able to understand and provide signed and dated written informed consent prior to screening
Exclusion Criteria
- Any pre-existing mental, physical, or substance abuse disorder which, 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
- Currently take and/or anticipated need for EFV, NVP, FPV/RTV or TPV/RTV during the study
- Treatment with any of the following medications within 15 days of starting study drug, or anticipated to need, during the course of the study: Etravirine (unless co-administered with LPV/RTV or DRV/RTV), rifampin, rifabutin, phenytoin, phenobarbital, barbiturates, glucocorticoids, modafinil, oxcarbazepine, pioglitazone, troglitazone, carbamazepine, St. Johns wort
- Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives
- History of ongoing or clinically relevant pancreatitis or hepatitis within the previous 6 months
- Expected to require treatment for HCV infection during the first 24 weeks of the study
- Evidence of cirrhosis with or without hepatitis viral co-infection
- History of upper gastrointestinal bleed and/or active peptic ulcer disease
- Screening haemoglobin 5xULN
- Screening ALT 3xULN and bilirubin 1.5xULN (with 35% direct bilirubin)
- Personal or family history of prolonged QT syndrome.
- Any clinically significant finding, as specified in the protocol, on screening or baseline electrocardiograph (ECG)
- History of allergy to the study drugs or their components or drugs of their class
- Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or future need of treatment with these agents during the study
- Treatment with immunomodulators within 28 days prior to screening or subject has received an HIV-1 vaccine within 90 days prior to screening
Data sourced from ClinicalTrials.gov (NCT00950859). 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.