Phase 3
Completed N=725
A Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed Dose Combination (FDC) Versus a Regimen Consisting of Darunavir/Cobicistat FDC With Emtricitabine/Tenofovir Disoproxil Fumarate FDC in Treatment-naive HIV Type 1 Infected Subjects
Immunodeficiency Virus Type 1, Human
Source: ClinicalTrials.gov NCT02431247 ↗
Enrolled (actual)
725
Serious AEs
9.9%
Results posted
Sep 2018
Primary outcomePrimary: Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach — 91.4; 88.4 percentage of participants — p=< 0.001
◆ Published Evidence
Established
85citations · ~11 / year
A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.
Summary
The purpose of this study is to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus Darunavir/Cobicistat (DRV/COBI) FDC coadministered with Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral (ARV) treatment naive adult participants.
Linked Publications (5)
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A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.
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Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.
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Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.
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Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study.
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Population Pharmacokinetic Analysis of Darunavir and Tenofovir Alafenamide in HIV-1-Infected Patients on the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen (AMBER and EMERALD Studies).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach |
91.4; 88.4 | < 0.001 sig |
| SECONDARY Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach |
82.6; 79.3; 92.8; 90.6; 76.2; 83.5 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm |
82.6; 79.9; 91.2; 88.7; 93.1; 91.7 | — |
| SECONDARY Change From Baseline in log10 HIV-1 RNA Levels at Week 48 |
-2.95; -2.91 | = 0.437 |
| SECONDARY Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 |
190.49; 172.01 | = 0.213 |
| SECONDARY Change From Baseline in Serum Creatinine at Week 48 |
0.05; 0.09 | < 0.001 sig |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48 |
-6.04; -9.16 | < 0.001 sig |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48 |
-5.16; -11.20 | < 0.001 sig |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48 |
5.32; 2.92 | = 0.001 sig |
| SECONDARY Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 |
4.7; 4.4; 0.6; 1.7; 4.7; 5.8 | — |
| SECONDARY Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 |
-15.72; -10.53 | = 0.033 sig |
| SECONDARY Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48 |
-0.58; -0.15 | = 0.033 sig |
| SECONDARY Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48 |
7.00; 35.02 | < 0.001 sig |
| SECONDARY Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48 |
-30.42; 18.36 | < 0.001 sig |
| SECONDARY Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48 |
16.00; 22.55 | = 0.147 |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir |
87909.3282 | — |
| SECONDARY Predose (Trough) Plasma Concentration (C0h) of Darunavir |
1898.9100 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide |
132.3117 | — |
| SECONDARY Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide |
11.9785 | — |
| SECONDARY Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) |
0.29; -1.66; -1.34; -3.43; 0.17; -2.69 | < 0.001 sig |
| SECONDARY Change From Baseline in BMD T-score of Hip and Spine |
0.019; -0.109; -0.121; -0.322; 0.015; -0.177 | — |
| SECONDARY Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 |
-3.2; 12.0; -1.1; 15.1 | — |
| SECONDARY Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 |
1.892; 24.679; 0.065; 24.251 | — |
| SECONDARY Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 |
0.047; 0.283; 0.046; 0.226 | — |
| SECONDARY Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 |
0.113; 0.777; -0.004; 0.633 | — |
| SECONDARY Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 |
12.7; 22.1; 16.9; 28.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach |
85.1; 94.2 | — |
| SECONDARY Change From Reference in log10 HIV-1 RNA Levels at Week 96 |
-2.72; -0.0027 | — |
| SECONDARY Change From Reference in CD4+ Cell Count at Week 96 |
228.85; 27.01 | — |
| SECONDARY Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability |
87.2; 82.6; 92.2; 88.7 | — |
| SECONDARY Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 |
11.6; 3.7; 0.8; 1.4; 10.8; 2.7 | — |
| SECONDARY Change From Reference in Serum Creatinine |
0.045; -0.034 | — |
| SECONDARY Change From Reference in eGFRcr by CKD-EPI Formula |
-5.6; 2.3 | — |
| SECONDARY Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula |
-5.2; 4.6 | — |
| SECONDARY Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula |
4.4; 0 | — |
| SECONDARY Change From Reference in UPCR |
-15.46; -1.40 | — |
| SECONDARY Change From Reference in UACR |
-0.70; -0.49 | — |
| SECONDARY Change From Reference in URBPCR |
13.70; -35.53 | — |
| SECONDARY Change From Reference in UB2MGCR |
-27.04; -40.53 | — |
| SECONDARY Percent Change From Reference in Urine FEPO4 |
18.52; -7.51 | — |
| SECONDARY Percent Change From Reference in Hip and Spine BMD |
-0.2565; 0.5467; -0.9349; 0.4829 | — |
| SECONDARY Change From Reference in BMD T-score of Hip and Spine at Week 96 |
-0.016; 0.025; -0.090; 0.034 | — |
| SECONDARY Change From Reference in ALP Levels |
-0.9; -9.7 | — |
| SECONDARY Change From Reference in Levels of Serum P1NP |
2.817; -11.963 | — |
| SECONDARY Change From Reference in Levels of Serum CTX |
0.041; -0.162 | — |
| SECONDARY Change From Reference in Levels of PTH |
-0.290; -1.283 | — |
| SECONDARY Change From Reference in Levels of 25-OH Vitamin D |
21.3; -10.3 | — |
| SECONDARY Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension |
97.7; 96.3; 99.0; 96.7; 98.1; 98.2 | — |
| SECONDARY Percentage of Participants With Protocol-defined Virologic Failure (PDVF) |
4.1; 0.6; 0.3; 0.6; 4.4; 0 | — |
| SECONDARY Percentage of Participants With PDVF Post-week 96 to End of Extension |
1.0; 2.1; 0; 0; 1.0; 1.4 | — |
| SECONDARY Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates |
100; 100; 99.6; 99.2; 99.6; 99.2 | — |
| SECONDARY Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates |
100; 100; 98.9; 97.4; 95.6; 94.1 | — |
| SECONDARY CD4+ Cell Count Post-Week From 96 to End of Extension |
790.2; 749.7; 779.4; 774.3; 789.8; 758.4 | — |
| SECONDARY Number of Participants With ARV Resistance |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension |
3.5; 5.2; 0; 1.3; 3.2; 4.8 | — |
Eligibility Criteria
Inclusion Criteria
- Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time
- Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to >=1,000 copies per milliliter (copies/mL)
- Cluster of Differentiation 4+ (CD4+) cell count >50 cells/microliter (cells/mcL)
- Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC
- Screening eGFRcreatinine >=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance
Exclusion Criteria
- Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening
- Subject has proven or suspected acute hepatitis within 30 days prior to screening
- Subject is hepatitis C or hepatitis B positive
- Subject has a history of cirrhosis
Data sourced from ClinicalTrials.gov (NCT02431247) and the linked publication. 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.