Clinical Trial Results:
A Phase 3, Randomized, Active-controlled, Open-label Study to Evaluate the Efficacy, Safety and Tolerability of Switching to a Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once-daily Single-tablet Regimen Versus Continuing the Current Regimen Consisting of a Boosted Protease Inhibitor (bPI) Combined with Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in Virologically-suppressed, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects
Summary
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EudraCT number |
2014-003052-31 |
Trial protocol |
BE SE GB ES PL FR |
Global end of trial date |
13 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Oct 2021
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First version publication date |
29 Oct 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TMC114IFD3013
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02269917 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Janssen Sciences Ireland UC
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Sponsor organisation address |
Barnahely, Cork, Ireland, P43 FA46
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Public contact |
Clinical Registry Group, Janssen Sciences Ireland UC, clinicaltrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Sciences Ireland UC, clinicaltrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Oct 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Oct 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) once-daily single-tablet regimen relative to continuing the current boosted protease inhibitor (bPI) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) in virologically-suppressed (human immunodeficiency virus-1 [HIV-1] Ribonucleic acid (RNA) less than [<] 50 copies per milliliter [copies per mL]) HIV-1 infected subjects, in regard to the proportion of virologic rebounders through Week 48, with a maximum allowable difference of 4 percent (%) (non-inferiority margin).
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCP) and applicable regulatory requirements. Safety was evaluated based on adverse events (AEs), clinical laboratory tests, physical examination, vital signs and bone mineral density (BMD).Safety was evaluated based on adverse events, clinical laboratory tests, physical examinations, vital signs, bone mineral density (BMD) of spine and hip and bone biomarkers in bone investigation sub-study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Apr 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 52
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Country: Number of subjects enrolled |
Canada: 66
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Country: Number of subjects enrolled |
Switzerland: 39
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Country: Number of subjects enrolled |
Spain: 169
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Country: Number of subjects enrolled |
France: 97
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Country: Number of subjects enrolled |
United Kingdom: 70
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Country: Number of subjects enrolled |
Poland: 126
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Country: Number of subjects enrolled |
Sweden: 28
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Country: Number of subjects enrolled |
United States: 494
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Worldwide total number of subjects |
1141
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EEA total number of subjects |
472
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1102
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From 65 to 84 years |
39
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 1149 subjects were enrolled in the study of which 1141 subjects received at least 1 dose of study drug and analyzed. Out of 1141 subjects, 963 subjects completed the study. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
BL to EOE-Test and BL to Switch-Control
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily up to Week 48. After Week 48, all subjectss continued to receive D/C/F/TAF treatment (that is, initial switch to D/C/F/TAF group) up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available up to 42 months. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Darunavir (DRV) 800 mg/ cobicistat 150 mg/ emtricitabine 200 mg/ tenofovir alafenamide 10 mg (D/C/F/TAF) FDC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet, Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single oral tablet of D/C/F/TAF 800/150/200/10 mg FDC once daily.
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Arm title
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Control | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received a boosted protease inhibitor (bPI) (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) up to Week 48. | ||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Boosted protease inhibitor (bPIs) (DRV or atazanavir with low-dose ritonavir [rtv] or cobicistat, or lopinavir with rtv) combined with F/TDF
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subject received a single oral tablet of bPIs and F/TDF once daily.
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Period 2
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Period 2 title |
Switch to D/C/F/TAF (until EOE)
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
Arms
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Arm title
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Switch to D/C/F/TAF | ||||||||||||||||||||||||||||||||||||
Arm description |
After Week 52, subjects earlier receiving treatment with bPI+F/TDF switched to D/C/F/TAF up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available for up to 42 months. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
D/C/F/TAF
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single oral tablet of D/C/F/TAF FDC once daily.
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Out of 378 subjects in the DRV/COBI+ F/TDF (Control) group, 352 subjects switched to D/C/F/TAF treatment after Week 52. |
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Baseline characteristics reporting groups
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Reporting group title |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE])
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Reporting group description |
Subjects received a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily up to Week 48. After Week 48, all subjectss continued to receive D/C/F/TAF treatment (that is, initial switch to D/C/F/TAF group) up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available up to 42 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Subjects received a boosted protease inhibitor (bPI) (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) up to Week 48. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE])
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Reporting group description |
Subjects received a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily up to Week 48. After Week 48, all subjectss continued to receive D/C/F/TAF treatment (that is, initial switch to D/C/F/TAF group) up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available up to 42 months. | ||
Reporting group title |
Control
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Reporting group description |
Subjects received a boosted protease inhibitor (bPI) (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) up to Week 48. | ||
Reporting group title |
Switch to D/C/F/TAF
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Reporting group description |
After Week 52, subjects earlier receiving treatment with bPI+F/TDF switched to D/C/F/TAF up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available for up to 42 months. | ||
Subject analysis set title |
Darunavir 800 mg
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Subjects received a single oral dose of DRV 800 mg as part of the DCFTAF FDC once daily up to Week 48.
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End point title |
Percentage of Subjects with Virologic Rebound (Human Immunodeficiency Virus [HIV]-1 RNA Greater Than or Equal to [>=] 50 copies/mL) Cumulative Through Week 48 | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 Ribonucleic Acid (RNA) level greater than or equal to (>=)50 copies per milliliter (copies/mL) up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason). Percentage of subjects with virologic rebound were reported. The intent-to-treat (ITT) analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
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End point type |
Primary
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End point timeframe |
Through Week 48
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
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Number of subjects included in analysis |
1141
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mantel-Haenszel | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
0.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.5 | ||||||||||||
upper limit |
2.2 |
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End point title |
Percentage of Subjects with Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=20 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason). Percentage of subjects with virologic rebound were reported. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Through 48 Weeks
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=200 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=200 copies/mL at premature discontinuation (irrespective of reason). Percentage of subjects with virologic rebound were reported. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Through 48 Weeks
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Time to Virologic Rebound at Week 48 | ||||||||||||
End point description |
Percentage of subjects with time to virologic rebound by Kaplan-Meier estimates were reported. Time to virologic rebound was calculated from baseline until the first rebound time point (that is, time point before confirmation of rebound). Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=50 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason). Here Kaplan-Meier estimates percentage of non-virologic rebound at week 96 were presented. The ITT analysis set included all subjects who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 48
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation due to AEs Through Week 48 | ||||||||||||||||||||||||
End point description |
An AE is any untoward medical occurrence in subjects who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to Week 48
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Serum Creatinine Levels at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed. ITT analysis set included all subjects randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this endpoint; and ‘n’ specifies subjects analyzed for this endpoint at given time point.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 24 and 48
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
Change at Week 48
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Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
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Number of subjects included in analysis |
1139
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.34 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Least Square (LS) Mean Difference | ||||||||||||||||||
Point estimate |
0.62
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.65 | ||||||||||||||||||
upper limit |
1.88 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.646
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||
Statistical analysis description |
Change at Week 48
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Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
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Number of subjects included in analysis |
1139
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.34 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Least Square (LS) Mean Difference | ||||||||||||||||||
Point estimate |
0.62
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.65 | ||||||||||||||||||
upper limit |
1.88 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.646
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End point title |
Change from Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Change from baseline in eGFRcr (by Cockcroft-Gault formula) was assessed at Weeks 24 and 48. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)*(weight in kilogram [kg])/72*(serum creatinine in milligram per deciliter [mg/dL])=eGFRcr (milliliter per minute [mL/min]); Female: (140 - age in years)*(weight in kg)/72*(serum creatinine in mg/dL)*0.85=eGFRcr (mL/min). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this endpoint; and ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 24 and 48
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
Change at Week 24
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Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
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Number of subjects included in analysis |
1139
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.506 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.58
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.3 | ||||||||||||||||||
upper limit |
1.13 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.874
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||
Statistical analysis description |
Change Week 48
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Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
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Number of subjects included in analysis |
1139
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.392 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.74
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-2.43 | ||||||||||||||||||
upper limit |
0.95 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.862
|
|
|||||||||||||||||||
End point title |
Change from Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Change from baseline in eGFRcr (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (<=)0.7 mg/dL: 144*(Scr/0.7)^-0.329*0.993age; 2) Scr greater than (>)0.7 mg/dL: 144*(Scr/0.7)^-1.209*0.993age. Male: 1) Scr <=0.9 mg/dL: 141*(Scr/0.9)^-0.411*0.993age; 2) Scr >0.9 mg/dL: 141*(Scr/0.9)^-1.209*0.993age. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this endpoint; and ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
Change at Week 24
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.143 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.92
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-2.14 | ||||||||||||||||||
upper limit |
0.31 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.624
|
||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||
Statistical analysis description |
Change at Week 48
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.092 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-1.09
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-2.36 | ||||||||||||||||||
upper limit |
0.18 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.646
|
|
|||||||||||||||||||
End point title |
Change from Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Change from baseline in eGFRcyst (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) <=0.8 mg/L: 133*(Scyst/0.8)^-0.499*0.996age (*0.932 if female); 2) Scyst >0.8 mg/L: 133*(Scyst/0.8)^-1.328*0.996age (*0.932 if female). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
Change at Week 24
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.054 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
1.14
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.02 | ||||||||||||||||||
upper limit |
2.29 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.59
|
||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||
Statistical analysis description |
Change at Week 48
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.034 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
1.34
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.1 | ||||||||||||||||||
upper limit |
2.57 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.63
|
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 | ||||||||||||||||||||||||||||||
End point description |
Change from baseline in UACR and UPCR was assessed at Weeks 24 and 48. Lower levels of albumin or protein in the urine indicates better proximal tubular function. The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study. Here, N (number of subjects analyzed) signifies subjects evaluated for this endpoint and ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UACR - Change at Week 24
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1139
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UACR - Change at Week 48
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1139
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 3 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UPCR - Change at Week 24
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1139
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 4 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UPCR - Change at Week 48
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1139
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 | ||||||||||||||||||||||||||||||
End point description |
Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this endpoint and ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||||||||||||||
Statistical analysis description |
URBPCR: Change at Week 24
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1119
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||||||||||||||
Statistical analysis description |
URBPCR: Change at Week 48
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1119
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 3 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UB2MGCR: Change at Week 24
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1119
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 4 | ||||||||||||||||||||||||||||||
Statistical analysis description |
UB2MGCR: Change at Week 48
|
||||||||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1119
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||
End point title |
Percent Change from Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
FEPO4 - Change at Week 24
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.288 | ||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
FEPO4 - Change at Week 48
|
||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||
Number of subjects included in analysis |
1141
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
other | ||||||||||||||||||
P-value |
= 0.148 | ||||||||||||||||||
Method |
Van Elteren Test | ||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||
End point title |
Percentage of Subjects with Virologic Response based on HIV-1 RNA less Than (<)20, <50, and <200 copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach | |||||||||||||||||||||
End point description |
Percentage of subjects with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 48 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as HIV-1 RNA <20/50/200 copies/mL (observed case). The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 48
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of Subjects with Virologic Response based on HIV-1 RNA <20, <50, and <200 copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | |||||||||||||||||||||
End point description |
Percentage of subjects with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 48 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA <20/50/200 copies/mL. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 48
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Change from Baseline in Cluster of Differentiation 4 plus (CD4+) Cell Count at Weeks 24 and 48 | |||||||||||||||||||||
End point description |
Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this endpoint and ‘n’ specifies those subjects who were analyzed for this endpoint at given time point.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 | ||||||||||||
End point description |
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1). The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates the number of subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 48
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence of >95% (Approach 2) Through Week 48 | ||||||||||||
End point description |
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 48, whichever came sooner (Approach 2). The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates the number of subjects evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 48
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Subjects with Resistance to Study Drug | |||||||||
End point description |
HIV-1 genotypes were analyzed from samples of subjects with confirmed virologic rebound (virologic rebound was defined as: confirmed HIV-1 RNA >=50 copies/mL up to, and including the upper bound of the Week 48 window) and with HIV-1 RNA value greater than or equal to (>=)400 copies/mL or who discontinued with last HIV-1 RNA >=400 copies/mL. Number of subjects who developed resistance to any of the study drug was determined. The ITT population with confirmed virologic rebound and with HIV-1 RNA value >=400 copies/mL was analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Week 48
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Predose (trough) Plasma Concentration (C0h) of Darunavir | ||||||||||||||||||||||
End point description |
Predose (trough) plasma concentration (C0h) of darunavir was determined. Pharmacokinetic (PK) data was only analyzed for subjects in the D/C/F/TAF group as per planned analysis. The PK analysis set included all subjects randomized to D/C/F/TAF group and received at least 1 dose of study drug in study, and for whom plasma concentration data of any analytes of interest were available. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Predose at Weeks 2, 4, 8, 12, 24, 36, and 48
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percent Change from Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 | ||||||||||||||||||||||||
End point description |
Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48. The bone investigation substudy (BIS) analysis set included all subjects who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percent Change from Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48. The bone investigation substudy (BIS) analysis set included all subjects who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percent Change from Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 | ||||||||||||||||||
End point description |
Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48. BIS analysis set included all subjects who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percent Change from Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 | ||||||||||||||||||||||||
End point description |
Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48. BIS analysis set included all subjects who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||||||||
Statistical analysis description |
Spine BMD: Percent change at Week 24
|
||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
1.37
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.697 | ||||||||||||||||||||||||
upper limit |
2.037 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.34
|
||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||||||||
Statistical analysis description |
Spine BMD: Percent change at Week 48
|
||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
2.05
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.277 | ||||||||||||||||||||||||
upper limit |
2.814 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.39
|
||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 3 | ||||||||||||||||||||||||
Statistical analysis description |
Hip BMD: Percent change at Week 24
|
||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
0.9
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.366 | ||||||||||||||||||||||||
upper limit |
1.436 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.272
|
||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 4 | ||||||||||||||||||||||||
Statistical analysis description |
Hip BMD: Percent change at Week 48
|
||||||||||||||||||||||||
Comparison groups |
D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) v Control
|
||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
1.7
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.144 | ||||||||||||||||||||||||
upper limit |
2.248 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.28
|
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 | |||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline in spine, hip, and femoral neck BMD T-Score was assessed at Week (Wk) 24 and 48. T-score values >= -1.0 were considered normal, T-score values < -1.0 to -2.5 indicate osteopenia and T-score values < -2.5 indicate osteoporosis. BIS analysis set included all subjects who were randomized and received at least 1 dose of study drug in the study, and had at least one postbaseline value for biomarker data. Here ‘n’ specifies subjects who were analyzed for this endpoint at given time point.
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 24 and 48
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Virologic Rebound (HIV-1 RNA >=20 copies/mL) Cumulative Through Week 96 [1] | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of subjects with virologic rebound were reported. Intent-to-treat (ITT) analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 96
|
||||||||||||
Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Virologic Rebound (HIV-1 RNA >=50 copies/mL) Cumulative Through Week 96 [2] | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=50 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=50copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of subjects with virologic rebound were reported. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 96
|
||||||||||||
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Virologic Rebound (HIV-1 RNA >=200 copies/mL) Cumulative Through Week 96 [3] | ||||||||||||
End point description |
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=200 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=200 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=200 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of subjects with virologic rebound were reported. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 96
|
||||||||||||
Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Time to Virologic Rebound at Week 96 [4] | ||||||||||||
End point description |
Percentage of subjects with time to virologic rebound by Kaplan-Meier estimates were reported. Time to virologic rebound (confirmed plasma HIV-1 RNA level >=50 copies/mL up to and including Week 96, last available on-treatment [single] HIV-1 RNA >=50 copies/mL at premature discontinuation [irrespective of reason], and last available on-treatment HIV-1 RNA >=50 copies/mL at the study cutoff of Week 96) was calculated from reference until the first rebound time point (that is, time point before confirmation of rebound) up to Week 96 visit. Here Kaplan-Meier estimates percentage of non-virologic rebound at week 96 are presented. The ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
|
||||||||||||
Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of Subjects with Virologic Response based on HIV-1 RNA <20, <50, and <200 copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach [5] | |||||||||||||||||||||
End point description |
Percentage of subjects with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as having last available HIV-1 RNA <20/50/200 copies/mL (observed case). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
|
|||||||||||||||||||||
Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
||||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of Subjects with Virologic Response based on HIV-1 RNA <20, <50, and <200 copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm [6] | |||||||||||||||||||||
End point description |
Percentage of subjects with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA <20/50/200 copies/mL. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
|
|||||||||||||||||||||
Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
||||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of Subjects with Virologic Failure based on HIV-1 RNA >=20, >=50, and >=200 copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach [7] | |||||||||||||||||||||
End point description |
Percentage of subjects with virologic failure based on HIV-1 RNA >=20, >=50, and >=200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic failure was defined by the FDA snapshot approach as having last available HIV-1 RNA >=20/50/200 copies/mL at Week 96; virologic failure - leading to discontinuation; virologic failure - discontinued due to other reason and last available HIV-1 RNA >=20/50/200 copies/mL. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, 99999 refers that confidential interval was not calculated as none of the subjects had HIV RNA <200 copies/mL.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
|
|||||||||||||||||||||
Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
||||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in CD4+ Cell Count at Week 96 [8] | ||||||||||||
End point description |
Change from reference in CD4+ cell count was assessed at Week 96. The change from reference in CD4+ count at a given time point is defined as: CD4+ at a given time point minus reference CD4+. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Based on NC=F analysis with values after discontinuation imputed with the reference value. Other (intermittent) missing values are imputed using LOCF.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF (Comprising 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52])
|
||||||||||||
Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects with Resistance to Study Drug Through Week 96 | ||||||||||||||||||||||||
End point description |
HIV-1 genotypes were analyzed from samples of subjects with confirmed virologic rebound in case they had HIV-1 RNA values >=400 copies/mL at failure or at later time points including subjects who discontinued with last HIV-1 RNA>=400 copies/mL. Virologic rebound: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA>=20 copies/mL at premature discontinuation (irrespective of reason) and last available on-treatment HIV-1 RNA>=20 copies/mL at study cutoff of Week 96. Number of subjects who developed resistance to any study drug (DRV, FTC and TFV/TAF) were reported. ITT analysis set: all randomized subjects and received at least one dose of study treatment in study. Here, N (number of subjects analyzed) signifies total number of subjects with screening/baseline and endpoint genotype. Due to low proportion of rebounders of which majority had low viral load values, few samples were eligible for postbaseline genotyping.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence of >95 (Approach 1) Through 96 Weeks [9] | ||||||||||||
End point description |
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 96 (Approach 1). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates the number of subjects evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
|
||||||||||||
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence of >95% (Approach 2) Through 96 Weeks [10] | ||||||||||||
End point description |
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 96, whichever came sooner (Approach 2). ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, 'N' (number of subjects analyzed) indicates the number of subjects evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
|
||||||||||||
Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Experiencing Grade 3 and 4 AEs, SAEs, and Premature Discontinuation due to AEs Through 96 Weeks [11] | ||||||||||||||||||||||||
End point description |
AE is any untoward medical occurrence in subjects who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize subject and/or may require medical or surgical intervention to prevent one of the outcomes listed above. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
|
||||||||||||||||||||||||
Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in Serum Creatinine Levels at Week 96 [12] | ||||||||||||
End point description |
Change from reference in serum creatinine levels at Week 96 was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis. For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference. The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96 [13] | ||||||||||||
End point description |
Change from reference in eGFRcr (by Cockcroft-Gault formula) was assessed at Week 96. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)*(weight in kilogram [kg])/72*(serum creatinine in milligram per deciliter [mg/dL])=eGFRcr (milliliter per minute [mL/min]); Female: (140 - age in years)*(weight in kg)/72*(serum creatinine in mg/dL)*0.85=eGFRcr (mL/min). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96 [14] | ||||||||||||
End point description |
Change from reference in eGFRcr (by CKD-EPI) was assessed at Week 96. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or
equal to (<=)0.7 mg/dL: 144*(Scr/0.7)^-0.329*0.993^age; 2) Scr greater than (>)0.7 mg/dL: 144*(Scr/0.7)^-1.209*0.993^age. Male: 1) Scr <=0.9 mg/dL: 141*
(Scr/0.9)^-0.411*0.993^age; 2) Scr >0.9 mg/dL: 141*(Scr/0.9)^-1.209*0.993^age. For the D/C/F/TAF group, reference is the comparative treatment phase
baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference
(reference 2). The ITT analysis set included all the subjects who were randomized and subjects at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96 [15] | ||||||||||||
End point description |
Change from reference in eGFRcyst (by CKD-EPI) was assessed at Week 96. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) <=0.8 mg/L: 133*(Scyst/0.8)^-0.499*0.996^age (*0.932 if female); 2) Scyst >0.8 mg/L: 133*(Scyst/0.8)^-1.328*0.996^age (*0.932 if female). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and subjects at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in UACR at Week 96 [16] | ||||||||||||
End point description |
Change from reference in UACR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in URBPCR at Week 96 [17] | ||||||||||||
End point description |
Change from reference in URBPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in UPCR at Week 96 [18] | ||||||||||||
End point description |
Change from reference in UPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Reference in UB2MGCR at Week 96 [19] | ||||||||||||
End point description |
Change from reference in UB2MGCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percent Change from Reference in FEPO4 at Week 96 | ||||||||||||
End point description |
Percent change from reference in FEPO4 at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percent change From Reference in Levels of Serum P1NP at Week 96 [20] | ||||||||||||
End point description |
Percent change from reference in serum P1NP levels at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percent change From Reference in Levels of Serum CTX at Week 96 [21] | ||||||||||||
End point description |
Percent change from reference in serum CTX at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percent change From Reference in Levels of PTH at Week 96 [22] | ||||||||||||
End point description |
Percent change from reference in PTH at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percent change From Reference in Levels of 25-OH Vitamin D at Week 96 [23] | ||||||||||||
End point description |
Percent change from reference in 25-OH Vitamin D at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2). BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||
Notes [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percent Change From Reference in Hip and Spine BMD at Week 96 [24] | ||||||||||||||||||
End point description |
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DXA scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from reference in hip and spine BMD was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2) BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this outcome measure; and ‘n’ specifies subjects analyzed for specified categories.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||||||||
Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change From Reference in BMD T-score of Hip and Spine at Week 96 [25] | ||||||||||||||||||
End point description |
BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2) BIS analysis set included all subjects who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'N' (number of subjects analyzed) signifies subjects evaluated for specified categories.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
|
||||||||||||||||||
Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects with Time to Protocol-defined Virologic Rebound by Kaplan-Meier Estimates [26] | ||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with time to protocol-defined virologic rebound by kaplan-meier estimates were reported. Virologic rebound is defined as subjects who show confirmed HIV-1 RNA >=50 copies/mL, or for which the last available (single) HIV-1 RNA value on treatment was >=50 copies/mL. Time to protocol-defined virologic rebound is defined as the time (in weeks) calculated from reference until the first rebound time point (time point before confirmation of rebound). Here, Kaplan-Meier estimates (%) of non-virologic rebound at every 6 months interval are presented. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this outcome measure; and ‘n’ specifies subjects analyzed for specified timepoints.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 96 to end of extension (at every 6 months, up to 42 months)
|
||||||||||||||||||||||||||||||||||||
Notes [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects with Time to Treatment Failure by Kaplan-Meier Estimates [27] | ||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with time to treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic rebound or having discontinued for reasons other than alternate access to D/C/F/TAF (or other antiretroviral [ARV]). The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this outcome measure; and ‘n’ specifies subjects analyzed for specified timepoints.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 96 to end of extension (at every 6 months, up to 42 months)
|
||||||||||||||||||||||||||||||||||||
Notes [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects with HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension [28] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with HIV RNA <50, <20, <200 copies/mL post Week 96 to end of extension were reported. The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study. Here, N (number of subjects analyzed) indicates number of subjects evaluable for this outcome measure; and ‘n’ specifies subjects analyzed for specified timepoints.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 96 to end of extension (up to 42 months)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
CD4+ Cell Count Post-Week 96 to end of Extension [29] | |||||||||||||||||||||||||||||||||
End point description |
The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed. The ITT analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study. Here, N (number of subjects analyzed) signifies subjects evaluated for this outcome measure and n (number analyzed) signifies subjects analyzed for this outcome measure at specified category.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Week 96 to end of extension (up to 42 months)
|
|||||||||||||||||||||||||||||||||
Notes [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence of >95% From Week 96 to End of extension [30] | ||||||||||||
End point description |
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability and was calculated cumulative from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in subjects who returned all dispensed bottles prior to or at the last visit in the study from Week 96 to end of extension. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment. Here, N (number of subjects analyzed) indicates the number of subjects evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 96 to end of extension (up to 42 months)
|
||||||||||||
Notes [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation due to AEs Post-Week 96 to end of Extension [31] | ||||||||||||||||||||||||
End point description |
AE is any untoward medical occurrence in subjects who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize subject and/or may require medical or surgical intervention to prevent one of the outcomes listed above. ITT analysis set included all the subjects who were randomized and received at least 1 dose of study treatment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Week 96 to end of extension (up to 42 months)
|
||||||||||||||||||||||||
Notes [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analyzed for specified arms only. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Up to 65 months
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Adverse event reporting additional description |
The intent-to-treat (ITT) analysis set included all the subjects who were randomized and received at least one dose of study treatment in the study.
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
D/C/F/TAF (Test)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily up to Week 48. After Week 48, all subjectss continued to receive D/C/F/TAF treatment (that is, initial switch to D/C/F/TAF group) up to Week 96. After Week 96, subjects were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available up to 42 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Switch to D/C/F/TAF Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
After Week 52, subjects earlier receiving treatment with bPI+F/TDF switched to D/C/F/TAF up to Week 96. After Week 96, sarticipants were given the opportunity to continue D/C/F/TAF treatment until D/C/F/TAF became commercially available for up to 42 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received a boosted protease inhibitor (bPI) (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (F/TDF) up to Week 48. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Dec 2014 |
The overall reason for the Protocol Amendment-2 was the design of a separate efficacy study in treatment-naïve human immunodeficiency virus type 1 (HIV-1) infected subjects and a re-orientation of the present study into a 48-week safety study. The timing of virologic HIV-1 ribonucleic acid (RNA) retesting was also amended upon regulatory request. |
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06 Mar 2015 |
The overall reason for the Protocol Amendment-3 was the change of the primary endpoint into an efficacy endpoint. |
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29 May 2015 |
The overall reason for the Protocol Amendment-4 was the increase in sample size to approximately 1,100 subjects, in order to yield enough power with an expected rebound rate reassessed from 2 percent (%) to 4%. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The limitation of the study was the open-label design. |