Phase 3
Completed N=30
Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir
Source: ClinicalTrials.gov NCT01568892 ↗Enrolled (actual)
30
Serious AEs
30.0%
Results posted
Feb 2014
Primary outcomePrimary: Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 — -1.06; 0.10 Log 10 copies per milliliter (c/mL) — p=<0.001
Summary
Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo- controlled, functional monotherapy phase to quantify the antiviral activity attributable to dolutegravir (DTG) in HIV-1 infected, ART-experienced adults who are experiencing virological failure on an Integrase inhibitor containing regimen (current RAL or ELV failures), with evidence of genotypic resistance to RAL or ELV at study entry. Thirty subjects will be randomized (1:1) to receive either DTG 50mg BID (Arm A) or Placebo (Arm B) with the current failing regimen for 7 days (RAL or ELV should be discontinued prior to dosing with DTG). At Day 8, subjects from both arms will enter an open label phase and receive open label DTG 50mg BID with an optimized background regimen containing at least one fully active drug.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 |
-1.06; 0.10 | <0.001 sig |
| SECONDARY Absolute Values in Plasma HIV-1 RNA Over Time |
4.02; 4.42; 2.95; 4.39; 2.14; 2.30 | — |
| SECONDARY Mean Change From Baseline in Plasma HIV-1 RNA Over Time |
4.02; 4.42; -1.07; -0.03; -1.87; -2.12 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time |
0; 0; 1; 0; 6; 6 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time |
2; 0; 4; 0; 9; 12 | — |
| SECONDARY Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time |
163.5; 90.5; 198.5; 102.0; 174.0; 234.0 | — |
| SECONDARY Median Change From Baseline in CD4+ Cell Counts Over Time |
163.5; 90.5; 7.0; 0.0; 14.0; 68.5 | — |
| SECONDARY Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time |
896.0; 808.5; 1135.0; 973.0; 1198.0; 1184.0 | — |
| SECONDARY Median Change From Baseline in CD8+ Cell Counts Over Time |
896.0; 808.5; 227.0; 177.0; 151.0; 288.0 | — |
| SECONDARY Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT]) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade |
0; 4; 7; 6; 2; 3 | — |
| SECONDARY Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade |
5; 4; 5; 5; 0; 4 | — |
| SECONDARY Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade |
2; 3; 2; 5; 0; 1 | — |
| SECONDARY AUC(0-tau) of DTG |
37.9 | — |
| SECONDARY Cmax of DTG |
4.14 | — |
| SECONDARY Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24 |
3.043; 1.393; 2.154; 1.864; 2.201; 1.820 | — |
| SECONDARY Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance |
4; 1; 1; 0; 2; 1 | — |
| SECONDARY Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance |
0; 1; 4; 0 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment Due to AEs |
2; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings |
1; 1 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
120.4; 113.4; 2.0; 2.8; -0.7; 3.1 | — |
| SECONDARY Change From Baseline in Heart Rate |
72.5; 75.9; -1.4; 0.7; 2.2; -2.5 | — |
| SECONDARY Change From Baseline in Albumin Level |
43.1; 43.4; 0.0; 0.0; 1.3; -0.8 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase |
91.9; 114.9; 1.9; -1.2; -6.1; -0.6 | — |
| SECONDARY Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels |
10.0; 7.5; 0.8; -1.1; -0.2; 2.1 | — |
| SECONDARY Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen |
3.819; 4.725; 0.433; 0.538; 0.308; 0.585 | — |
| SECONDARY Change From Baseline in Creatinine Clearance |
106.8; 104.8; -13.0; -10.5; -10.4; -12.0 | — |
| SECONDARY Change From Baseline in Lipase Levels |
29.1; 34.0; 3.4; 12.5; 3.3; 17.7 | — |
| SECONDARY Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Count |
0.016; 0.015; 0.006; 0.002; 0.005; 0.004 | — |
| SECONDARY Change From Baseline in Hemoglobin Level |
132.9; 129.9; -1.0; -1.3; -2.5; -0.9 | — |
| SECONDARY Change From Baseline in Hematocrit Level |
0.4024; 0.3974; -0.0015; -0.0049; -0.0066; -0.0043 | — |
| SECONDARY Change From Baseline in Mean Corpuscle Volume |
99.1; 97.8; 0.1; 0.3; 1.2; 0.3 | — |
| SECONDARY Change From Baseline in Red Blood Cell Count |
4.09; 4.09; 0.00; -0.04; -0.08; -0.06 | — |
Eligibility Criteria
Inclusion Criteria
- Screening plasma HIV-1 RNA ≥1000 copies/mL
- ART-experienced, INI-experienced, DTG naïve
- Current virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen
- The subject's HIV-1 shows genotypic resistance to RAL or ELV at Screening
- Subject has been on stable ART for at least one month prior to Screening and through Day 1(with exceptions for ETV, EFV and NVP that can be interrupted within 14 days of Day 1, see Exclusion Criterion)
- Documented resistance to at least one drug from each of two or more of any approved classes of ART other than integrase inhibitors
- Be able to receive at least one fully active drug as part of the OBR from Day 8
- Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
- Willing and able to understand and provide signed and dated written informed consent prior to Screening.
Exclusion Criteria
- Women who are pregnant or breast feeding
- An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ 5 times the upper limit of normal (ULN) at Screening
- ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening
Data sourced from ClinicalTrials.gov (NCT01568892). 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.