Phase 3
Completed N=499
A Study to Determine Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) in Human Immunodeficiency Virus (HIV)-1 Infected Antiretroviral Therapy (ART) Naïve Women (ARIA)
Infection, Human Immunodeficiency Virus · HIV
Source: ClinicalTrials.gov NCT01910402 ↗
Enrolled (actual)
499
Serious AEs
7.0%
Results posted
Oct 2016
Primary outcomePrimary: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 — 82; 71 Percentage of participants — p=0.005
Summary
This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 |
82; 71 | 0.005 sig |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time-Randomized Phase |
0; 0; 64; 13; 81; 49 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL in Continuation Phase |
100; 100 | — |
| SECONDARY Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase |
-2.591; -1.923; -2.756; -2.541; -2.789; -2.726 | — |
| SECONDARY Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase |
-2.911; -3.107 | — |
| SECONDARY Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase |
4.481; 4.441; 1.895; 2.516; 1.748; 1.908 | — |
| SECONDARY Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase |
1.591; 1.590 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Randomized Phase |
94.9; 73.7; 143.8; 124.4; 200.6; 163.0 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Continuation Phase |
286.5; 254.7 | — |
| SECONDARY Absolute Values in CD4+ Cell Count at Indicated Timepoints-Randomized Phase |
369.7; 380.3; 465.0; 455.1; 509.5; 506.2 | — |
| SECONDARY Absolute Values in CD4+ Cell Count at Indicated Timepoints-Continuation Phase |
635.3; 553.0 | — |
| SECONDARY Change From Baseline in Carbon Dioxide, Electrolytes, Lipids, Glucose, Urea at Indicated Time Points |
-0.4; 0.6; -0.2; 0.8; -0.5; 0.3 | — |
| SECONDARY Change From Baseline in Bilirubin and Creatinine at Indicated Timepoints |
-0.8; 27.2; -0.6; 22.8; -0.2; 25 | — |
| SECONDARY Change From Baseline in Albumin at Indicated Timepoints |
0.1; -0.5; 0.5; 0.1; 1.4; 0.8 | — |
| SECONDARY Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase at Indicated Time Points |
-3.3; -3.4; -5.2; -2.3; -5.4; -3.7 | — |
| SECONDARY Change From Baseline in Creatinine Clearance at Indicated Time Points |
-16.3; -7.5; -17.3; -7; -16.2; -9.1 | — |
| SECONDARY Change From Baseline in Lipase at Indicated Timepoints |
-1.2; -1.3; -2.2; -2.1; -6; -6 | — |
| SECONDARY Change From Baseline in Total CHLS/HDL CHLS Ratio at Indicated Timepoints |
0.1264; 0.2159; -0.2736; -0.1092; -0.3098; -0.1922 | — |
| SECONDARY Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes at Indicated Time Points |
0.003; 0.003; 0.002; 0.003; 0.004; 0.003 | — |
| SECONDARY Change From Baseline in Erythrocytes at Indicated Time Points |
-0.04; -0.07; -0.07; -0.09; -0.08; -0.09 | — |
| SECONDARY Change From Baseline in Hematocrit Count at Indicated Time Points |
0.0003; -0.0042; 0.0081; 0.0000; 0.0157; 0.0051 | — |
| SECONDARY Change From Baseline in Erythrocyte Mean Corpuscular Volume at Indicated Time Points |
0.9; 0.5; 3.4; 1.9; 5.5; 3.1 | — |
| SECONDARY Change From Baseline in Triglycerides at Week 48 |
0.045; 0.070 | 0.7053 |
| SECONDARY Change From Baseline in TC/HDL Ratio at Week 48 |
-0.264; -0.158 | 0.3165 |
| SECONDARY Change From Baseline in Urine Albumin Creatinine Ratio at Indicated Time Points |
-1.15; -1.03; -0.68; -0.10 | — |
| SECONDARY Number of Participants With AEs by Maximum Toxicity-Randomized Phase |
79; 60; 94; 91; 18; 37 | — |
| SECONDARY Number of Participants With AEs by Maximum Toxicity-Continuation Phase |
32; 48; 7; 6 | — |
| SECONDARY Number of Participants With Any Adverse Events (AEs), and Serious Adverse Events (SAEs)-Randomized Phase |
195; 197; 12; 20 | — |
| SECONDARY Number of Participants With Any AEs, and SAEs in Continuation Phase |
93; 13 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Randomized Phase |
17; 11; 16; 9; 4; 3 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Continuation Phase |
24; 9; 3; 0; 2; 0 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Randomized Phase |
7; 21; 2; 3; 1; 1 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Continuation Phase |
5; 1; 0; 0; 2; 0 | — |
| SECONDARY Number of Participants Who Withdrew From Treatment Due to AEs-Randomized Phase |
10; 17 | — |
| SECONDARY Number of Participants Who Withdrew From Treatment Due to AEs-Continuation Phase |
4 | — |
| SECONDARY Change From Baseline in Bone Specific Alkaline Phosphatase, Osteocalcin and Procollagen 1 N-terminal Propeptide at Indicated Timepoints |
1.33; 6.00; 2.64; 7.60; 3.73; 14.38 | — |
| SECONDARY Change From Baseline in Type I Collagen C-telopeptides at Indicated Timepoints |
89.8; 272.4; 75.9; 267.9 | — |
| SECONDARY Change From Baseline in Vitamin D, Vitamin D2 and Vitamin D3 at Week 24 and Week 48 |
1.8; 16.3; -1.9; 8.9; 0.3; 1.0 | — |
| SECONDARY Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-terminal Propeptide, Type 1 Collagen C-Telopeptide, Vitamin D Ratio of Week 48 Results Over Baseline |
1.188; 1.629; 1.214; 1.752; 1.282; 2.039 | <0.001 sig |
| SECONDARY Change From Baseline at Week 48 in SF-12 Total Score, MCS and PCS |
0.0; 0.1; 2.397; 2.329; 1.905; 1.444 | — |
| SECONDARY HIVTSQs Total Score at Indicated Timepoints |
54.0; 51.9; 56.1; 53.6; 56.8; 54.3 | 0.016 sig |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 by Subgroups |
80; 71; 92; 74; 86; 80 | — |
| SECONDARY Number of Participants With Post-Baseline HIV-1 Disease Progression-Randomized Phase |
5; 4; 1; 2; 0; 0 | — |
| SECONDARY Number of Participants With Post-Baseline HIV-1 Disease Progression for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase) |
6; 1; 0; 2 | — |
| SECONDARY Number of Participants With Treatment Emergent Resistances for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase) |
0; 1; 1; 0 | — |
| SECONDARY Number of Participants With Treatment Emergent Resistances for ATV 300 mg+RTV 100 mg+TDF 300 mg/FTC 200mg QD (Randomized Phase) |
1; 0; 1; 0 | — |
Eligibility Criteria
Inclusion Criteria
- HIV-1 infected females (gender at birth) >=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 Screening plasma HIV-1 RNA >=500 c/mL.
- Documentation that the subject is negative for the HLA-B*5701 allele.
- Antiretroviral-naïve ( 35% direct bilirubin)
- Subject has CrCL of <50 mL/min via Cockroft-Gault method
- Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for subjects with bundle branch block.
Data sourced from ClinicalTrials.gov (NCT01910402). 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.