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A Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed Dose Combination (FDC) Versus a Regimen Consisting of Darunavir/Cobicistat FDC With Emtricitabine/Tenofovir Disoproxil Fumarate FDC in Treatment-naive HIV Type 1 Infected Subjects

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ClinicalTrials.gov Identifier: NCT02431247
Recruitment Status : Active, not recruiting
First Posted : April 30, 2015
Results First Posted : September 14, 2018
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Immunodeficiency Virus Type 1, Human
Interventions Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC
Drug: DRV/COBI FDC
Drug: FTC/TDF FDC
Drug: D/C/F/TAF FDC - Matching Placebo
Drug: FTC/TDF FDC Matching Placebo
Drug: DRV/COBI FDC Matching Placebo
Enrollment 725
Recruitment Details  
Pre-assignment Details Results are reported through Week 48 (primary analysis). Complete data through final analysis (through Week 96 and follow-up) will be reported within 1 year of end of trial date when final data based on study completion date will be available.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48. Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Period Title: Overall Study
Started 362 363
Completed 0 0
Not Completed 362 363
Reason Not Completed
Lost to Follow-up             5             5
Adverse Event             8             15
Physician Decision             3             0
Withdrawal by Subject             4             6
Other             2             1
Ongoing             339             336
Non-compliance with study drug             1             0
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control) Total
Hide Arm/Group Description Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48. Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48. Total of all reporting groups
Overall Number of Baseline Participants 362 363 725
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 362 participants 363 participants 725 participants
35.6  (10.17) 35.1  (9.99) 35.3  (10.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 363 participants 725 participants
Female
44
  12.2%
41
  11.3%
85
  11.7%
Male
318
  87.8%
322
  88.7%
640
  88.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 363 participants 725 participants
Hispanic or Latino
50
  13.8%
45
  12.4%
95
  13.1%
Not Hispanic or Latino
310
  85.6%
316
  87.1%
626
  86.3%
Unknown or Not Reported
2
   0.6%
2
   0.6%
4
   0.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 363 participants 725 participants
American Indian or Alaska Native
1
   0.3%
2
   0.6%
3
   0.4%
Asian
4
   1.1%
7
   1.9%
11
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
40
  11.0%
40
  11.0%
80
  11.0%
White
300
  82.9%
300
  82.6%
600
  82.8%
More than one race
3
   0.8%
6
   1.7%
9
   1.2%
Unknown or Not Reported
14
   3.9%
8
   2.2%
22
   3.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 363 participants 725 participants
Asian
4
   1.1%
7
   1.9%
11
   1.5%
Black or African American
40
  11.0%
40
  11.0%
80
  11.0%
Hispanic or Latino
41
  11.3%
38
  10.5%
79
  10.9%
Other
19
   5.2%
18
   5.0%
37
   5.1%
White Non-Hispanic
258
  71.3%
260
  71.6%
518
  71.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 363 participants 725 participants
Belgium
14
   3.9%
12
   3.3%
26
   3.6%
Canada
14
   3.9%
18
   5.0%
32
   4.4%
France
22
   6.1%
28
   7.7%
50
   6.9%
Germany
46
  12.7%
42
  11.6%
88
  12.1%
Italy
37
  10.2%
44
  12.1%
81
  11.2%
Poland
35
   9.7%
43
  11.8%
78
  10.8%
Russia
39
  10.8%
47
  12.9%
86
  11.9%
Spain
82
  22.7%
55
  15.2%
137
  18.9%
United Kingdom
7
   1.9%
7
   1.9%
14
   1.9%
United States
66
  18.2%
67
  18.5%
133
  18.3%
1.Primary Outcome
Title Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach
Hide Description Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA greater than or equal to [>=] 20/50/200 copies per mL at Week 48), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.
Time Frame At Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
91.4
(88.1 to 94.1)
88.4
(84.7 to 91.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments One-sided p-value for non-inferiority of Test versus Control arm. The non-inferiority margin is 10%.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
-1.6 to 7.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Less Than 20 and 200 Copies Per mL at Week 48 Defined by FDA Snapshot Approach
Hide Description Percentage of participants with HIV-1 RNA < 20/200 copies per mL using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA >= 20/50/200 copies per mL at Week 48 ), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.
Time Frame At Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Less than 20 Copies per mL
82.6
(78.3 to 86.4)
79.3
(74.8 to 83.4)
Less than 200 Copies per mL
92.8
(89.7 to 95.3)
90.6
(87.2 to 93.4)
3.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Hide Description Percentage of participants with HIV-1 RNA less than 20, 50, and 200 copies per mL at Week 48 based on TLOVR algorithm were assessed. TLOVR requires sustained HIV-1 RNA < 50 copies per mL; confirmed HIV-1 RNA >= 50 copies per mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation.
Time Frame At Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Less than 20 Copies per mL
82.6
(78.3 to 86.4)
79.9
(75.4 to 83.9)
Less than 50 Copies per mL
91.2
(87.8 to 93.9)
88.7
(85.0 to 91.8)
Less than 200 Copies per mL
93.1
(90.0 to 95.5)
91.7
(88.4 to 94.4)
4.Secondary Outcome
Title Change From Baseline in log10 HIV-1 RNA Levels at Week 48
Hide Description Change from baseline in log10 HIV-1 RNA levels were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all participants who were randomized and received at least one dose of study treatment in study. Based on not completed (NC) equal to (=) failure (F) analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using last observation carried forward (LOCF).
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Least Squares Mean (Standard Error)
Unit of Measure: log10 HIV-1 RNA copies per mL
-2.95  (0.044) -2.91  (0.044)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.437
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.171 to 0.074
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.063
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48
Hide Description The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Week 48 were assessed.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Based on NC = F analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using LOCF.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Least Squares Mean (Standard Error)
Unit of Measure: Cells per millimeter cube (cells/mm^3)
190.49  (10.472) 172.01  (10.458)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.213
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 18.48
Confidence Interval (2-Sided) 95%
-10.595 to 47.550
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.808
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Antiretroviral (ARV) Resistance Through Week 48
Hide Description Number of participants with DRV, FTC, TDF/TAF resistance were reported.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Measure Type: Number
Unit of Measure: Participants
1 0
7.Secondary Outcome
Title Change From Baseline in Serum Creatinine at Week 48
Hide Description Change from baseline in serum creatinine at Week 48 was reported. Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 340 330
Least Squares Mean (Standard Error)
Unit of Measure: milligram per deciliter (mg/dL)
0.05  (0.006) 0.09  (0.006)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.05 to -0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.008
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48
Hide Description Change from baseline in eGFRcr was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) >= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcr was assessed by calculating serum creatinine (Scr) using the CKD-EPI equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m^2) = 144 x (Scr/0.7)^-0.329 x 0.993^age (Scr =< 0.7 mg/dL) and eGFRcr mL/min/1.73m^2 = 144 x (Scr/0.7)^-1.209 x 0.993^age (Scr >0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m^2 = 141 x (Scr/0.9)^-0.411 x 0.993^age (Scr =<0.9 mg/dL) and eGFRcr mL/min/1.73m^2 = 141 x (Scr/0.9)^-1.209 x 0.993^age (Scr >0.9 mg/dL) for male participants.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 340 330
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73 m^2
-6.04  (0.551) -9.16  (0.559)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.12
Confidence Interval (2-Sided) 95%
1.57 to 4.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.786
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48
Hide Description Change from baseline in eGFRcr by (cockcroft-gault formula) at Week 48. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl [mL/min] = (140 – A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit (kilogram [kg]), C is the serum concentration of creatinine [mg/dL], R = 1 if the participant is male and = 0.85 if female.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 340 330
Least Squares Mean (Standard Error)
Unit of Measure: milliliter per minute (mL/min)
-5.16  (0.790) -11.20  (0.802)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.04
Confidence Interval (2-Sided) 95%
3.83 to 8.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.126
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48
Hide Description Change from baseline in eGFRcyst was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) >= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the CKD-EPI equation: eGFRcyst mL/min/1.73m^2 = 133 x (Scyst/0,8)^-0.499 x 0.996^age [x 0.932 if female] (Scyst =<0.8 mg/L) and eGFRcr mL/min/1.73m^2 = 133 x (Scyst/0,8)^-1.328 x 0.996^age [x 0.932 if male] (Scyst >0.8 mg/L).
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 337 329
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73 m^2
5.32  (0.525) 2.92  (0.532)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
0.93 to 3.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.747
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events
Hide Description AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (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 participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame Up to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 362 363
Measure Type: Number
Unit of Measure: Percentage of participants
Grade 3 AEs 4.7 4.4
Grade 4 AEs 0.6 1.7
SAEs 4.7 5.8
Premature discontinuations due to AEs 1.9 4.4
12.Secondary Outcome
Title Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48
Hide Description Change from baseline in UPCR at Week 48 were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 336 325
Median (Full Range)
Unit of Measure: milligram per gram (mg/g)
-15.72
(-748.1 to 254.2)
-10.53
(-903.0 to 1546.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.033
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48
Hide Description Change from baseline in UACR at Week 48 were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 338 327
Median (Full Range)
Unit of Measure: mg/g
-0.58
(-226.5 to 143.8)
-0.15
(-640.4 to 969.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.003
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48
Hide Description Change from baseline in URBPCR at Week 48 were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 334 324
Median (Full Range)
Unit of Measure: microgram per gram (mcg/g)
7.00
(-1555.7 to 5183.8)
35.02
(-700.7 to 30350.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48
Hide Description Change from baseline in UB2MGCR at Week 48 were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 331 320
Median (Full Range)
Unit of Measure: mcg/g
-30.42
(-11818.6 to 3452.0)
18.36
(-2440.5 to 90832.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
16.Secondary Outcome
Title Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48
Hide Description Percent change from baseline in FEPO4 at Week 48 were reported.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 339 329
Median (Full Range)
Unit of Measure: Percent change
16.00
(-87.3 to 1756.6)
22.55
(-90.1 to 1720.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.147
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
17.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir
Hide Description The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post dose.
Time Frame 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) analysis set: all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of DRV was analyzed only for test arm as per planned analyses. 'N'(number of participants analyzed): number of participants evaluable for this outcome measure.
Arm/Group Title Darunavir 800 mg [D/C/F/TAF+ FTC/TDF (Test)]
Hide Arm/Group Description:
Participants received DRV 800 mg along with COBI 150 mg, FTC 200 mg, TAF 10 mg as a (D/C/F/TAF) FDC oral tablet once daily along with DRV/COBI FDC-matching placebo and FTC/TDF FDC-matching placebo tablets once daily up to Week 48.
Overall Number of Participants Analyzed 355
Mean (Standard Deviation)
Unit of Measure: hour*nanogram per milliliter (h*ng/mL)
87909.3282  (20232.09905)
18.Secondary Outcome
Title Predose (Trough) Plasma Concentration (C0h) of Darunavir
Hide Description C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.
Time Frame 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) analysis set: all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of DRV was analyzed only for test arm as per planned analyses. 'N'(number of participants analyzed): number of participants evaluable for this outcome measure.
Arm/Group Title Darunavir 800 mg [D/C/F/TAF+ FTC/TDF (Test)]
Hide Arm/Group Description:
Participants received DRV 800 mg along with COBI 150 mg, FTC 200 mg, TAF 10 mg as a (D/C/F/TAF) FDC oral tablet once daily along with DRV/COBI FDC-matching placebo and FTC/TDF FDC-matching placebo tablets once daily up to Week 48.
Overall Number of Participants Analyzed 355
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
1898.9100  (758.83837)
19.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide
Hide Description The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time Frame 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) analysis set: all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of TAF was analyzed only for test arm as per planned analyses. 'N'(number of participants analyzed): number of participants evaluable for this outcome measure.
Arm/Group Title Tenofovir Alafenamide 10 mg [D/C/F/TAF+ FTC/TDF (Test)]
Hide Arm/Group Description:
Participants received TAF 10 mg along with DRV 800 mg, COBI 150 mg, FTC 200 mg as a (D/C/F/TAF) FDC oral tablet once daily along with DRV/COBI FDC-matching placebo and FTC/TDF FDC-matching placebo tablets once daily up to Week 48.
Overall Number of Participants Analyzed 355
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
132.3117  (40.87742)
20.Secondary Outcome
Title Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide
Hide Description C0-2h is defined as as the plasma concentrations 2 hours after dosing.
Time Frame 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) analysis set: all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of TAF was analyzed only for test arm as per planned analyses. 'N'(number of participants analyzed): number of participants evaluable for this outcome measure.
Arm/Group Title Tenofovir Alafenamide 10 mg [D/C/F/TAF+ FTC/TDF (Test)]
Hide Arm/Group Description:
Participants received TAF 10 mg along with DRV 800 mg, COBI 150 mg, FTC 200 mg as a (D/C/F/TAF) FDC oral tablet once daily along with DRV/COBI FDC-matching placebo and FTC/TDF FDC-matching placebo tablets once daily up to Week 48.
Overall Number of Participants Analyzed 355
Mean (Standard Deviation)
Unit of Measure: ng/mL
11.9785  (11.86104)
21.Secondary Outcome
Title Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD)
Hide Description The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by dual energy x-ray absorptiometry (DEXA) scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from baseline in hip and spine BMD was assessed.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Bone investigation substudy (BIS) analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
Hip region BMD (Week 24) Number Analyzed 97 participants 82 participants
0.29  (0.248) -1.66  (0.269)
Spine region BMD (Week 24) Number Analyzed 96 participants 82 participants
-1.34  (0.285) -3.43  (0.309)
Hip region BMD (Week 48) Number Analyzed 96 participants 85 participants
0.17  (0.322) -2.69  (0.342)
Spine region BMD (Week 48) Number Analyzed 96 participants 85 participants
-0.68  (0.402) -2.38  (0.428)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments Hip region BMD (Week 24)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
1.227 to 2.678
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.368
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments Hip region BMD (Week 48)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.86
Confidence Interval (2-Sided) 95%
1.934 to 3.791
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.470
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments Spine region BMD (Week 24)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
1.259 to 2.919
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.421
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection D/C/F/TAF+ FTC/TDF (Test), DRV/COBI+ FTC/TDF (Control)
Comments Spine region BMD (Week 48)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
0.539 to 2.858
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.588
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in BMD T-score of Hip and Spine
Hide 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.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: BMD T-score
Hip region BMD T-score (Week 24) Number Analyzed 97 participants 82 participants
0.019  (0.0180) -0.109  (0.0157)
Spine region BMD T-score( Week 24) Number Analyzed 96 participants 82 participants
-0.121  (0.0259) -0.322  (0.0307)
Hip region BMD T-score (Week 48) Number Analyzed 96 participants 85 participants
0.015  (0.0213) -0.177  (0.0225)
Spine region BMD T-score( Week 48) Number Analyzed 96 participants 85 participants
-0.061  (0.0390) -0.225  (0.0386)
23.Secondary Outcome
Title Change From Baseline in Alkaline Phosphatase (ALP) Levels at Week 24 and 48
Hide Description Change from baseline in ALP at Week 24 and 48 were reported.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: Units per liter (U/L)
Week 24 Number Analyzed 103 participants 88 participants
-3.2  (1.17) 12.0  (1.74)
Week 48 Number Analyzed 97 participants 85 participants
-1.1  (1.29) 15.1  (2.00)
24.Secondary Outcome
Title Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Week 24 and 48
Hide Description Change from baseline in serum P1NP at Week 24 and 48 were reported.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: microgram per liter (mcg/L)
Week 24 Number Analyzed 101 participants 85 participants
1.892  (1.3754) 24.679  (2.0956)
Week 48 Number Analyzed 96 participants 84 participants
0.065  (1.6428) 24.251  (2.6337)
25.Secondary Outcome
Title Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Week 24 and 48
Hide Description Change from baseline in serum CTX at Week 24 and 48 were reported.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: mcg/L
Week 24 Number Analyzed 103 participants 83 participants
0.047  (0.0165) 0.283  (0.0251)
Week 48 Number Analyzed 97 participants 81 participants
0.046  (0.0174) 0.226  (0.0234)
26.Secondary Outcome
Title Change From Baseline in Levels of Parathyroid Hormone (PTH) at Week 24 and 48
Hide Description Change from baseline in PTH at Week 24 and 48 were reported.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: Picomol per liter (pmol/L)
Week 24 Number Analyzed 101 participants 83 participants
0.113  (0.2171) 0.777  (0.2401)
Week 48 Number Analyzed 95 participants 83 participants
-0.004  (0.2232) 0.633  (0.2155)
27.Secondary Outcome
Title Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48
Hide Description Change from baseline in 25-OH Vitamin D at Week 24 and 48 were reported.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
BIS analysis set included all participants 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 analyzed) signifies number of participants analyzed at specific timepoint.
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description:
Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48.
Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
Overall Number of Participants Analyzed 113 99
Mean (Standard Error)
Unit of Measure: nanomol per liter (nmol/L)
Week 24 Number Analyzed 101 participants 84 participants
12.7  (2.76) 22.1  (3.76)
Week 48 Number Analyzed 97 participants 82 participants
16.9  (2.84) 28.3  (3.15)
Time Frame Up to 48 Weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Hide Arm/Group Description Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48. Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48.
All-Cause Mortality
D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/362 (0.00%)   0/363 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   17/362 (4.70%)   21/363 (5.79%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/362 (0.28%)  0/363 (0.00%) 
Bone marrow oedema * 1  0/362 (0.00%)  1/363 (0.28%) 
Gastrointestinal disorders     
Anal fistula * 1  0/362 (0.00%)  1/363 (0.28%) 
Anogenital dysplasia * 1  1/362 (0.28%)  1/363 (0.28%) 
Colitis * 1  0/362 (0.00%)  1/363 (0.28%) 
General disorders     
Influenza like illness * 1  0/362 (0.00%)  1/363 (0.28%) 
Non-cardiac chest pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Pyrexia * 1  0/362 (0.00%)  1/363 (0.28%) 
Hepatobiliary disorders     
Cholangitis sclerosing * 1  0/362 (0.00%)  1/363 (0.28%) 
Infections and infestations     
Appendicitis * 1  2/362 (0.55%)  1/363 (0.28%) 
Herpes zoster * 1  1/362 (0.28%)  0/363 (0.00%) 
Influenza * 1  1/362 (0.28%)  0/363 (0.00%) 
Lung abscess * 1  1/362 (0.28%)  0/363 (0.00%) 
Papilloma viral infection * 1  0/362 (0.00%)  1/363 (0.28%) 
Pneumonia * 1  2/362 (0.55%)  1/363 (0.28%) 
Rectal abscess * 1  0/362 (0.00%)  1/363 (0.28%) 
Sepsis * 1  0/362 (0.00%)  1/363 (0.28%) 
Injury, poisoning and procedural complications     
Concussion * 1  1/362 (0.28%)  0/363 (0.00%) 
Foot fracture * 1  1/362 (0.28%)  0/363 (0.00%) 
Lumbar vertebral fracture * 1  1/362 (0.28%)  0/363 (0.00%) 
Tendon rupture * 1  1/362 (0.28%)  1/363 (0.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts * 1  1/362 (0.28%)  2/363 (0.55%) 
Hodgkin's disease * 1  1/362 (0.28%)  1/363 (0.28%) 
Squamous cell carcinoma of lung * 1  0/362 (0.00%)  1/363 (0.28%) 
Nervous system disorders     
Dizziness postural * 1  0/362 (0.00%)  1/363 (0.28%) 
Psychiatric disorders     
Suicidal ideation * 1  1/362 (0.28%)  0/363 (0.00%) 
Suicide attempt * 1  0/362 (0.00%)  2/363 (0.55%) 
Renal and urinary disorders     
Calculus urinary * 1  1/362 (0.28%)  0/363 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst ruptured * 1  1/362 (0.28%)  0/363 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  0/362 (0.00%)  2/363 (0.55%) 
Stevens-Johnson syndrome * 1  0/362 (0.00%)  1/363 (0.28%) 
Toxic skin eruption * 1  0/362 (0.00%)  2/363 (0.55%) 
Vascular disorders     
Thrombosis * 1  1/362 (0.28%)  0/363 (0.00%) 
1
Term from vocabulary, MedDRA Version 19.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
D/C/F/TAF+ FTC/TDF (Test) DRV/COBI+ FTC/TDF (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   311/362 (85.91%)   304/363 (83.75%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/362 (0.83%)  3/363 (0.83%) 
Hypochromic anaemia * 1  0/362 (0.00%)  1/363 (0.28%) 
Leukocytosis * 1  0/362 (0.00%)  2/363 (0.55%) 
Leukopenia * 1  1/362 (0.28%)  1/363 (0.28%) 
Lymphadenopathy * 1  8/362 (2.21%)  6/363 (1.65%) 
Neutropenia * 1  1/362 (0.28%)  3/363 (0.83%) 
Thrombocytopenia * 1  1/362 (0.28%)  0/363 (0.00%) 
Cardiac disorders     
Angina pectoris * 1  1/362 (0.28%)  1/363 (0.28%) 
Cardiovascular disorder * 1  1/362 (0.28%)  0/363 (0.00%) 
Palpitations * 1  0/362 (0.00%)  2/363 (0.55%) 
Congenital, familial and genetic disorders     
Type V hyperlipidaemia * 1  1/362 (0.28%)  1/363 (0.28%) 
Ear and labyrinth disorders     
Cerumen impaction * 1  1/362 (0.28%)  1/363 (0.28%) 
Ear canal erythema * 1  1/362 (0.28%)  0/363 (0.00%) 
Ear discomfort * 1  0/362 (0.00%)  1/363 (0.28%) 
Ear pain * 1  1/362 (0.28%)  0/363 (0.00%) 
Otorrhoea * 1  1/362 (0.28%)  0/363 (0.00%) 
Sudden hearing loss * 1  1/362 (0.28%)  1/363 (0.28%) 
Tinnitus * 1  2/362 (0.55%)  2/363 (0.55%) 
Tympanic membrane perforation * 1  1/362 (0.28%)  0/363 (0.00%) 
Vertigo * 1  8/362 (2.21%)  7/363 (1.93%) 
Endocrine disorders     
Goitre * 1  1/362 (0.28%)  0/363 (0.00%) 
Eye disorders     
Blepharitis * 1  1/362 (0.28%)  1/363 (0.28%) 
Cataract * 1  1/362 (0.28%)  0/363 (0.00%) 
Chalazion * 1  1/362 (0.28%)  1/363 (0.28%) 
Conjunctivitis allergic * 1  1/362 (0.28%)  0/363 (0.00%) 
Eye irritation * 1  1/362 (0.28%)  0/363 (0.00%) 
Eye pruritus * 1  1/362 (0.28%)  0/363 (0.00%) 
Eyelid oedema * 1  2/362 (0.55%)  0/363 (0.00%) 
Iridocyclitis * 1  0/362 (0.00%)  1/363 (0.28%) 
Ocular hyperaemia * 1  0/362 (0.00%)  1/363 (0.28%) 
Periorbital oedema * 1  1/362 (0.28%)  0/363 (0.00%) 
Retinal scar * 1  1/362 (0.28%)  0/363 (0.00%) 
Vision blurred * 1  0/362 (0.00%)  2/363 (0.55%) 
Visual acuity reduced * 1  1/362 (0.28%)  0/363 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  1/362 (0.28%)  3/363 (0.83%) 
Abdominal distension * 1  6/362 (1.66%)  1/363 (0.28%) 
Abdominal pain * 1  11/362 (3.04%)  13/363 (3.58%) 
Abdominal pain lower * 1  0/362 (0.00%)  1/363 (0.28%) 
Abdominal pain upper * 1  5/362 (1.38%)  8/363 (2.20%) 
Abnormal faeces * 1  0/362 (0.00%)  1/363 (0.28%) 
Aerophagia * 1  0/362 (0.00%)  1/363 (0.28%) 
Anal fissure * 1  0/362 (0.00%)  2/363 (0.55%) 
Anal fistula * 1  0/362 (0.00%)  1/363 (0.28%) 
Anal pruritus * 1  2/362 (0.55%)  1/363 (0.28%) 
Anal skin tags * 1  1/362 (0.28%)  0/363 (0.00%) 
Anogenital dysplasia * 1  1/362 (0.28%)  3/363 (0.83%) 
Anorectal discomfort * 1  1/362 (0.28%)  0/363 (0.00%) 
Anorectal disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Aphthous ulcer * 1  4/362 (1.10%)  1/363 (0.28%) 
Chronic gastritis * 1  0/362 (0.00%)  1/363 (0.28%) 
Colitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Constipation * 1  2/362 (0.55%)  3/363 (0.83%) 
Dental caries * 1  0/362 (0.00%)  1/363 (0.28%) 
Dental discomfort * 1  0/362 (0.00%)  1/363 (0.28%) 
Diarrhoea * 1  71/362 (19.61%)  66/363 (18.18%) 
Diarrhoea haemorrhagic * 1  1/362 (0.28%)  0/363 (0.00%) 
Dry mouth * 1  2/362 (0.55%)  1/363 (0.28%) 
Duodenitis * 1  0/362 (0.00%)  2/363 (0.55%) 
Dyspepsia * 1  12/362 (3.31%)  10/363 (2.75%) 
Enteritis * 1  3/362 (0.83%)  2/363 (0.55%) 
Enterocolitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Faeces soft * 1  0/362 (0.00%)  1/363 (0.28%) 
Flatulence * 1  7/362 (1.93%)  2/363 (0.55%) 
Food poisoning * 1  2/362 (0.55%)  1/363 (0.28%) 
Gastritis * 1  3/362 (0.83%)  4/363 (1.10%) 
Gastrooesophageal reflux disease * 1  4/362 (1.10%)  5/363 (1.38%) 
Gingival bleeding * 1  1/362 (0.28%)  0/363 (0.00%) 
Glossitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Haematochezia * 1  0/362 (0.00%)  1/363 (0.28%) 
Haemorrhoids * 1  6/362 (1.66%)  6/363 (1.65%) 
Haemorrhoids thrombosed * 1  0/362 (0.00%)  2/363 (0.55%) 
Hiatus hernia * 1  0/362 (0.00%)  1/363 (0.28%) 
Hyperchlorhydria * 1  1/362 (0.28%)  1/363 (0.28%) 
Inguinal hernia * 1  0/362 (0.00%)  1/363 (0.28%) 
Lip disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Mouth ulceration * 1  0/362 (0.00%)  1/363 (0.28%) 
Nausea * 1  28/362 (7.73%)  45/363 (12.40%) 
Odynophagia * 1  1/362 (0.28%)  1/363 (0.28%) 
Oral disorder * 1  1/362 (0.28%)  1/363 (0.28%) 
Oral pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Proctalgia * 1  2/362 (0.55%)  4/363 (1.10%) 
Proctitis * 1  2/362 (0.55%)  1/363 (0.28%) 
Rectal haemorrhage * 1  0/362 (0.00%)  2/363 (0.55%) 
Rectal tenesmus * 1  1/362 (0.28%)  0/363 (0.00%) 
Salivary gland calculus * 1  0/362 (0.00%)  1/363 (0.28%) 
Salivary gland pain * 1  1/362 (0.28%)  0/363 (0.00%) 
Sensitivity of teeth * 1  0/362 (0.00%)  2/363 (0.55%) 
Stomatitis * 1  0/362 (0.00%)  1/363 (0.28%) 
Tongue discolouration * 1  0/362 (0.00%)  2/363 (0.55%) 
Tongue dry * 1  0/362 (0.00%)  1/363 (0.28%) 
Tooth disorder * 1  2/362 (0.55%)  1/363 (0.28%) 
Toothache * 1  4/362 (1.10%)  3/363 (0.83%) 
Umbilical hernia * 1  1/362 (0.28%)  0/363 (0.00%) 
Vomiting * 1  15/362 (4.14%)  15/363 (4.13%) 
General disorders     
Asthenia * 1  14/362 (3.87%)  12/363 (3.31%) 
Chest discomfort * 1  1/362 (0.28%)  1/363 (0.28%) 
Chest pain * 1  1/362 (0.28%)  2/363 (0.55%) 
Chills * 1  0/362 (0.00%)  1/363 (0.28%) 
Cyst * 1  1/362 (0.28%)  0/363 (0.00%) 
Discomfort * 1  0/362 (0.00%)  1/363 (0.28%) 
Fatigue * 1  19/362 (5.25%)  18/363 (4.96%) 
Feeling hot * 1  2/362 (0.55%)  0/363 (0.00%) 
Inflammation * 1  0/362 (0.00%)  2/363 (0.55%) 
Influenza like illness * 1  7/362 (1.93%)  8/363 (2.20%) 
Malaise * 1  1/362 (0.28%)  4/363 (1.10%) 
Mass * 1  1/362 (0.28%)  0/363 (0.00%) 
Nodule * 1  1/362 (0.28%)  0/363 (0.00%) 
Non-cardiac chest pain * 1  2/362 (0.55%)  3/363 (0.83%) 
Oedema peripheral * 1  2/362 (0.55%)  1/363 (0.28%) 
Peripheral swelling * 1  1/362 (0.28%)  2/363 (0.55%) 
Pyrexia * 1  14/362 (3.87%)  16/363 (4.41%) 
Thirst * 1  1/362 (0.28%)  1/363 (0.28%) 
Xerosis * 1  0/362 (0.00%)  2/363 (0.55%) 
Hepatobiliary disorders     
Biliary colic * 1  1/362 (0.28%)  0/363 (0.00%) 
Cholecystitis chronic * 1  0/362 (0.00%)  1/363 (0.28%) 
Cholelithiasis * 1  0/362 (0.00%)  1/363 (0.28%) 
Hyperbilirubinaemia * 1  0/362 (0.00%)  2/363 (0.55%) 
Liver injury * 1  1/362 (0.28%)  0/363 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  2/362 (0.55%)  1/363 (0.28%) 
Immune reconstitution inflammatory syndrome * 1  1/362 (0.28%)  0/363 (0.00%) 
Seasonal allergy * 1  6/362 (1.66%)  2/363 (0.55%) 
Infections and infestations     
Abscess limb * 1  1/362 (0.28%)  1/363 (0.28%) 
Abscess oral * 1  0/362 (0.00%)  1/363 (0.28%) 
Acarodermatitis * 1  2/362 (0.55%)  1/363 (0.28%) 
Acute hepatitis C * 1  1/362 (0.28%)  1/363 (0.28%) 
Acute sinusitis * 1  0/362 (0.00%)  2/363 (0.55%) 
Amoebiasis * 1  1/362 (0.28%)  0/363 (0.00%) 
Amoebic dysentery * 1  0/362 (0.00%)  1/363 (0.28%) 
Anal abscess * 1  3/362 (0.83%)  1/363 (0.28%) 
Anal chlamydia infection * 1  0/362 (0.00%)  4/363 (1.10%) 
Angular cheilitis * 1  0/362 (0.00%)  3/363 (0.83%) 
Anorectal infection bacterial * 1  0/362 (0.00%)  1/363 (0.28%) 
Appendicitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Bacterial food poisoning * 1  0/362 (0.00%)  1/363 (0.28%) 
Bacterial vaginosis * 1  1/362 (0.28%)  0/363 (0.00%) 
Balanitis candida * 1  1/362 (0.28%)  0/363 (0.00%) 
Balanoposthitis infective * 1  1/362 (0.28%)  0/363 (0.00%) 
Body tinea * 1  2/362 (0.55%)  0/363 (0.00%) 
Breast abscess * 1  0/362 (0.00%)  2/363 (0.55%) 
Bronchitis * 1  14/362 (3.87%)  20/363 (5.51%) 
Carbuncle * 1  1/362 (0.28%)  0/363 (0.00%) 
Cellulitis * 1  3/362 (0.83%)  1/363 (0.28%) 
Cellulitis of male external genital organ * 1  1/362 (0.28%)  0/363 (0.00%) 
Chlamydial infection * 1  8/362 (2.21%)  9/363 (2.48%) 
Chronic hepatitis C * 1  0/362 (0.00%)  1/363 (0.28%) 
Conjunctivitis * 1  5/362 (1.38%)  6/363 (1.65%) 
Conjunctivitis bacterial * 1  2/362 (0.55%)  0/363 (0.00%) 
Ear infection * 1  1/362 (0.28%)  0/363 (0.00%) 
Ecthyma * 1  1/362 (0.28%)  0/363 (0.00%) 
Enterocolitis viral * 1  0/362 (0.00%)  1/363 (0.28%) 
Epididymitis * 1  2/362 (0.55%)  2/363 (0.55%) 
Erysipelas * 1  1/362 (0.28%)  0/363 (0.00%) 
Eyelid infection * 1  1/362 (0.28%)  0/363 (0.00%) 
Folliculitis * 1  5/362 (1.38%)  8/363 (2.20%) 
Fungal infection * 1  0/362 (0.00%)  2/363 (0.55%) 
Fungal skin infection * 1  1/362 (0.28%)  6/363 (1.65%) 
Furuncle * 1  1/362 (0.28%)  3/363 (0.83%) 
Gastroenteritis * 1  17/362 (4.70%)  14/363 (3.86%) 
Gastroenteritis viral * 1  1/362 (0.28%)  2/363 (0.55%) 
Gastrointestinal infection * 1  1/362 (0.28%)  0/363 (0.00%) 
Genital herpes * 1  5/362 (1.38%)  5/363 (1.38%) 
Genital herpes simplex * 1  1/362 (0.28%)  0/363 (0.00%) 
Genital infection fungal * 1  0/362 (0.00%)  1/363 (0.28%) 
Genitourinary chlamydia infection * 1  0/362 (0.00%)  1/363 (0.28%) 
Gingivitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Gonorrhoea * 1  12/362 (3.31%)  15/363 (4.13%) 
Groin abscess * 1  1/362 (0.28%)  0/363 (0.00%) 
Helicobacter gastritis * 1  1/362 (0.28%)  0/363 (0.00%) 
Helicobacter infection * 1  0/362 (0.00%)  2/363 (0.55%) 
Hepatitis A * 1  1/362 (0.28%)  1/363 (0.28%) 
Hepatitis C * 1  1/362 (0.28%)  1/363 (0.28%) 
Herpes simplex * 1  2/362 (0.55%)  1/363 (0.28%) 
Herpes virus infection * 1  1/362 (0.28%)  3/363 (0.83%) 
Herpes zoster * 1  5/362 (1.38%)  3/363 (0.83%) 
Herpes zoster infection neurological * 1  1/362 (0.28%)  0/363 (0.00%) 
Hordeolum * 1  2/362 (0.55%)  0/363 (0.00%) 
Infection parasitic * 1  0/362 (0.00%)  1/363 (0.28%) 
Influenza * 1  11/362 (3.04%)  10/363 (2.75%) 
Latent tuberculosis * 1  1/362 (0.28%)  0/363 (0.00%) 
Lice infestation * 1  1/362 (0.28%)  0/363 (0.00%) 
Localised infection * 1  1/362 (0.28%)  1/363 (0.28%) 
Molluscum contagiosum * 1  2/362 (0.55%)  1/363 (0.28%) 
Mycoplasma genitalium infection * 1  1/362 (0.28%)  1/363 (0.28%) 
Nasopharyngitis * 1  40/362 (11.05%)  31/363 (8.54%) 
Onychomycosis * 1  1/362 (0.28%)  3/363 (0.83%) 
Oral candidiasis * 1  4/362 (1.10%)  5/363 (1.38%) 
Oral fungal infection * 1  0/362 (0.00%)  1/363 (0.28%) 
Oral hairy leukoplakia * 1  1/362 (0.28%)  1/363 (0.28%) 
Oral herpes * 1  7/362 (1.93%)  6/363 (1.65%) 
Orchitis * 1  2/362 (0.55%)  0/363 (0.00%) 
Oropharyngeal candidiasis * 1  1/362 (0.28%)  0/363 (0.00%) 
Oropharyngeal gonococcal infection * 1  3/362 (0.83%)  1/363 (0.28%) 
Otitis externa * 1  0/362 (0.00%)  1/363 (0.28%) 
Otitis media * 1  1/362 (0.28%)  3/363 (0.83%) 
Overgrowth bacterial * 1  0/362 (0.00%)  1/363 (0.28%) 
Papilloma viral infection * 1  1/362 (0.28%)  1/363 (0.28%) 
Paronychia * 1  0/362 (0.00%)  1/363 (0.28%) 
Periodontitis * 1  1/362 (0.28%)  2/363 (0.55%) 
Pertussis * 1  0/362 (0.00%)  1/363 (0.28%) 
Pharyngeal chlamydia infection * 1  1/362 (0.28%)  0/363 (0.00%) 
Pharyngitis * 1  15/362 (4.14%)  15/363 (4.13%) 
Pharyngitis streptococcal * 1  1/362 (0.28%)  1/363 (0.28%) 
Pneumonia * 1  3/362 (0.83%)  0/363 (0.00%) 
Proctitis bacterial * 1  1/362 (0.28%)  1/363 (0.28%) 
Proctitis chlamydial * 1  4/362 (1.10%)  0/363 (0.00%) 
Proctitis gonococcal * 1  1/362 (0.28%)  3/363 (0.83%) 
Pulpitis dental * 1  2/362 (0.55%)  0/363 (0.00%) 
Pyelonephritis chronic * 1  1/362 (0.28%)  0/363 (0.00%) 
Respiratory tract infection * 1  11/362 (3.04%)  10/363 (2.75%) 
Respiratory tract infection viral * 1  1/362 (0.28%)  1/363 (0.28%) 
Rhinitis * 1  9/362 (2.49%)  5/363 (1.38%) 
Schistosomiasis * 1  0/362 (0.00%)  1/363 (0.28%) 
Secondary syphilis * 1  0/362 (0.00%)  3/363 (0.83%) 
Sexually transmitted disease * 1  0/362 (0.00%)  1/363 (0.28%) 
Sexually transmitted disease carrier * 1  0/362 (0.00%)  1/363 (0.28%) 
Sinusitis * 1  6/362 (1.66%)  5/363 (1.38%) 
Subcutaneous abscess * 1  3/362 (0.83%)  1/363 (0.28%) 
Syphilis * 1  17/362 (4.70%)  19/363 (5.23%) 
Tinea cruris * 1  1/362 (0.28%)  1/363 (0.28%) 
Tinea infection * 1  1/362 (0.28%)  0/363 (0.00%) 
Tinea pedis * 1  2/362 (0.55%)  2/363 (0.55%) 
Tinea versicolour * 1  1/362 (0.28%)  0/363 (0.00%) 
Tonsillitis * 1  9/362 (2.49%)  8/363 (2.20%) 
Tooth abscess * 1  2/362 (0.55%)  3/363 (0.83%) 
Tracheitis * 1  2/362 (0.55%)  1/363 (0.28%) 
Trichomoniasis * 1  0/362 (0.00%)  1/363 (0.28%) 
Upper respiratory tract infection * 1  20/362 (5.52%)  22/363 (6.06%) 
Urethritis * 1  6/362 (1.66%)  6/363 (1.65%) 
Urethritis chlamydial * 1  2/362 (0.55%)  0/363 (0.00%) 
Urethritis gonococcal * 1  1/362 (0.28%)  0/363 (0.00%) 
Urinary tract infection * 1  3/362 (0.83%)  4/363 (1.10%) 
Vaginal infection * 1  0/362 (0.00%)  1/363 (0.28%) 
Varicella * 1  0/362 (0.00%)  1/363 (0.28%) 
Viral infection * 1  6/362 (1.66%)  2/363 (0.55%) 
Viral pharyngitis * 1  0/362 (0.00%)  1/363 (0.28%) 
Viral rhinitis * 1  0/362 (0.00%)  1/363 (0.28%) 
Viral tonsillitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Viral upper respiratory tract infection * 1  2/362 (0.55%)  3/363 (0.83%) 
Vulvovaginal candidiasis * 1  0/362 (0.00%)  2/363 (0.55%) 
Vulvovaginitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Injury, poisoning and procedural complications     
Alcohol poisoning * 1  0/362 (0.00%)  2/363 (0.55%) 
Ankle fracture * 1  1/362 (0.28%)  0/363 (0.00%) 
Arthropod bite * 1  2/362 (0.55%)  1/363 (0.28%) 
Brain contusion * 1  1/362 (0.28%)  0/363 (0.00%) 
Concussion * 1  0/362 (0.00%)  1/363 (0.28%) 
Contusion * 1  4/362 (1.10%)  3/363 (0.83%) 
Face injury * 1  1/362 (0.28%)  0/363 (0.00%) 
Fall * 1  1/362 (0.28%)  0/363 (0.00%) 
Foot fracture * 1  0/362 (0.00%)  1/363 (0.28%) 
Hand fracture * 1  1/362 (0.28%)  0/363 (0.00%) 
Laceration * 1  1/362 (0.28%)  1/363 (0.28%) 
Ligament sprain * 1  3/362 (0.83%)  1/363 (0.28%) 
Limb injury * 1  1/362 (0.28%)  2/363 (0.55%) 
Lower limb fracture * 1  0/362 (0.00%)  1/363 (0.28%) 
Mouth injury * 1  0/362 (0.00%)  1/363 (0.28%) 
Muscle strain * 1  0/362 (0.00%)  1/363 (0.28%) 
Periorbital haemorrhage * 1  1/362 (0.28%)  0/363 (0.00%) 
Post procedural complication * 1  0/362 (0.00%)  2/363 (0.55%) 
Procedural nausea * 1  1/362 (0.28%)  0/363 (0.00%) 
Skin abrasion * 1  0/362 (0.00%)  2/363 (0.55%) 
Tendon rupture * 1  1/362 (0.28%)  0/363 (0.00%) 
Tooth fracture * 1  2/362 (0.55%)  1/363 (0.28%) 
Toxicity to various agents * 1  2/362 (0.55%)  1/363 (0.28%) 
Traumatic haematoma * 1  1/362 (0.28%)  0/363 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/362 (0.28%)  1/363 (0.28%) 
Amylase increased * 1  2/362 (0.55%)  0/363 (0.00%) 
Anal pap smear abnormal * 1  0/362 (0.00%)  1/363 (0.28%) 
Aspartate aminotransferase increased * 1  0/362 (0.00%)  2/363 (0.55%) 
Beta 2 microglobulin increased * 1  0/362 (0.00%)  4/363 (1.10%) 
Beta 2 microglobulin urine abnormal * 1  0/362 (0.00%)  1/363 (0.28%) 
Beta 2 microglobulin urine increased * 1  2/362 (0.55%)  5/363 (1.38%) 
Blood 1,25-dihydroxycholecalciferol decreased * 1  0/362 (0.00%)  2/363 (0.55%) 
Blood 25-hydroxycholecalciferol decreased * 1  0/362 (0.00%)  1/363 (0.28%) 
Blood cholesterol increased * 1  8/362 (2.21%)  2/363 (0.55%) 
Blood creatine phosphokinase increased * 1  1/362 (0.28%)  4/363 (1.10%) 
Blood creatinine increased * 1  0/362 (0.00%)  2/363 (0.55%) 
Blood iron decreased * 1  0/362 (0.00%)  1/363 (0.28%) 
Blood parathyroid hormone increased * 1  1/362 (0.28%)  2/363 (0.55%) 
Blood potassium decreased * 1  0/362 (0.00%)  1/363 (0.28%) 
Blood pressure increased * 1  1/362 (0.28%)  2/363 (0.55%) 
Blood testosterone decreased * 1  1/362 (0.28%)  0/363 (0.00%) 
Blood triglycerides increased * 1  5/362 (1.38%)  1/363 (0.28%) 
Bone density decreased * 1  2/362 (0.55%)  1/363 (0.28%) 
Bone density increased * 1  0/362 (0.00%)  1/363 (0.28%) 
Creatinine renal clearance decreased * 1  3/362 (0.83%)  7/363 (1.93%) 
Cystatin C abnormal * 1  0/362 (0.00%)  1/363 (0.28%) 
Gamma-glutamyltransferase increased * 1  0/362 (0.00%)  2/363 (0.55%) 
Heart rate decreased * 1  1/362 (0.28%)  0/363 (0.00%) 
Heart rate increased * 1  0/362 (0.00%)  1/363 (0.28%) 
Human papilloma virus test positive * 1  0/362 (0.00%)  1/363 (0.28%) 
Lipids increased * 1  0/362 (0.00%)  1/363 (0.28%) 
Low density lipoprotein increased * 1  6/362 (1.66%)  0/363 (0.00%) 
Lymphocyte morphology abnormal * 1  0/362 (0.00%)  1/363 (0.28%) 
Neutrophil count decreased * 1  1/362 (0.28%)  0/363 (0.00%) 
Neutrophil count increased * 1  0/362 (0.00%)  1/363 (0.28%) 
Smear cervix abnormal * 1  0/362 (0.00%)  1/363 (0.28%) 
Vitamin D decreased * 1  7/362 (1.93%)  2/363 (0.55%) 
Weight decreased * 1  3/362 (0.83%)  3/363 (0.83%) 
Weight increased * 1  2/362 (0.55%)  3/363 (0.83%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  4/362 (1.10%)  4/363 (1.10%) 
Dehydration * 1  1/362 (0.28%)  0/363 (0.00%) 
Diabetes mellitus * 1  1/362 (0.28%)  0/363 (0.00%) 
Dyslipidaemia * 1  3/362 (0.83%)  1/363 (0.28%) 
Hypercholesterolaemia * 1  5/362 (1.38%)  2/363 (0.55%) 
Hyperglycaemia * 1  3/362 (0.83%)  3/363 (0.83%) 
Hyperlipidaemia * 1  2/362 (0.55%)  3/363 (0.83%) 
Hypertriglyceridaemia * 1  1/362 (0.28%)  3/363 (0.83%) 
Hypokalaemia * 1  0/362 (0.00%)  1/363 (0.28%) 
Hypophosphataemia * 1  0/362 (0.00%)  2/363 (0.55%) 
Increased appetite * 1  2/362 (0.55%)  1/363 (0.28%) 
Iron deficiency * 1  0/362 (0.00%)  1/363 (0.28%) 
Vitamin D deficiency * 1  15/362 (4.14%)  13/363 (3.58%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  11/362 (3.04%)  11/363 (3.03%) 
Axillary mass * 1  0/362 (0.00%)  1/363 (0.28%) 
Back pain * 1  10/362 (2.76%)  8/363 (2.20%) 
Bone pain * 1  2/362 (0.55%)  0/363 (0.00%) 
Bursitis * 1  1/362 (0.28%)  2/363 (0.55%) 
Cervical spinal stenosis * 1  0/362 (0.00%)  1/363 (0.28%) 
Costochondritis * 1  1/362 (0.28%)  0/363 (0.00%) 
Flank pain * 1  1/362 (0.28%)  1/363 (0.28%) 
Groin pain * 1  1/362 (0.28%)  0/363 (0.00%) 
Intervertebral disc degeneration * 1  1/362 (0.28%)  0/363 (0.00%) 
Intervertebral disc protrusion * 1  1/362 (0.28%)  1/363 (0.28%) 
Jaw cyst * 1  0/362 (0.00%)  1/363 (0.28%) 
Joint swelling * 1  0/362 (0.00%)  2/363 (0.55%) 
Limb mass * 1  1/362 (0.28%)  0/363 (0.00%) 
Monarthritis * 1  0/362 (0.00%)  1/363 (0.28%) 
Muscle contracture * 1  2/362 (0.55%)  2/363 (0.55%) 
Muscle spasms * 1  1/362 (0.28%)  0/363 (0.00%) 
Muscle tightness * 1  1/362 (0.28%)  0/363 (0.00%) 
Muscular weakness * 1  2/362 (0.55%)  1/363 (0.28%) 
Musculoskeletal chest pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Musculoskeletal pain * 1  3/362 (0.83%)  5/363 (1.38%) 
Musculoskeletal stiffness * 1  0/362 (0.00%)  1/363 (0.28%) 
Myalgia * 1  3/362 (0.83%)  7/363 (1.93%) 
Neck pain * 1  5/362 (1.38%)  2/363 (0.55%) 
Osteoarthritis * 1  3/362 (0.83%)  0/363 (0.00%) 
Osteopenia * 1  17/362 (4.70%)  27/363 (7.44%) 
Osteoporosis * 1  6/362 (1.66%)  10/363 (2.75%) 
Pain in extremity * 1  2/362 (0.55%)  7/363 (1.93%) 
Periarthritis * 1  1/362 (0.28%)  0/363 (0.00%) 
Plantar fasciitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Rotator cuff syndrome * 1  0/362 (0.00%)  1/363 (0.28%) 
Spinal pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Synovial cyst * 1  1/362 (0.28%)  0/363 (0.00%) 
Tendon pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Tendonitis * 1  5/362 (1.38%)  2/363 (0.55%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acrochordon * 1  1/362 (0.28%)  0/363 (0.00%) 
Adenoma benign * 1  1/362 (0.28%)  0/363 (0.00%) 
Anogenital warts * 1  14/362 (3.87%)  13/363 (3.58%) 
Kaposi's sarcoma * 1  0/362 (0.00%)  1/363 (0.28%) 
Lipoma * 1  1/362 (0.28%)  0/363 (0.00%) 
Malignant melanoma * 1  1/362 (0.28%)  0/363 (0.00%) 
Melanocytic naevus * 1  3/362 (0.83%)  0/363 (0.00%) 
Papilloma * 1  1/362 (0.28%)  0/363 (0.00%) 
Seborrhoeic keratosis * 1  1/362 (0.28%)  0/363 (0.00%) 
Spinal cord neoplasm * 1  0/362 (0.00%)  1/363 (0.28%) 
Nervous system disorders     
Burning sensation * 1  0/362 (0.00%)  1/363 (0.28%) 
Carpal tunnel syndrome * 1  0/362 (0.00%)  1/363 (0.28%) 
Disturbance in attention * 1  2/362 (0.55%)  0/363 (0.00%) 
Dizziness * 1  3/362 (0.83%)  2/363 (0.55%) 
Dizziness exertional * 1  2/362 (0.55%)  0/363 (0.00%) 
Dizziness postural * 1  4/362 (1.10%)  2/363 (0.55%) 
Dysgeusia * 1  0/362 (0.00%)  1/363 (0.28%) 
Epilepsy * 1  2/362 (0.55%)  0/363 (0.00%) 
Headache * 1  47/362 (12.98%)  32/363 (8.82%) 
Hypoaesthesia * 1  2/362 (0.55%)  2/363 (0.55%) 
Memory impairment * 1  1/362 (0.28%)  1/363 (0.28%) 
Migraine * 1  4/362 (1.10%)  0/363 (0.00%) 
Motor dysfunction * 1  0/362 (0.00%)  1/363 (0.28%) 
Myoclonus * 1  1/362 (0.28%)  0/363 (0.00%) 
Neuropathy peripheral * 1  0/362 (0.00%)  1/363 (0.28%) 
Paraesthesia * 1  2/362 (0.55%)  1/363 (0.28%) 
Sciatica * 1  3/362 (0.83%)  0/363 (0.00%) 
Seizure * 1  1/362 (0.28%)  0/363 (0.00%) 
Somnolence * 1  3/362 (0.83%)  3/363 (0.83%) 
Tremor * 1  0/362 (0.00%)  2/363 (0.55%) 
Trigeminal neuralgia * 1  1/362 (0.28%)  0/363 (0.00%) 
Psychiatric disorders     
Abnormal dreams * 1  2/362 (0.55%)  2/363 (0.55%) 
Affective disorder * 1  1/362 (0.28%)  0/363 (0.00%) 
Agitation * 1  1/362 (0.28%)  0/363 (0.00%) 
Anxiety * 1  10/362 (2.76%)  6/363 (1.65%) 
Apathy * 1  0/362 (0.00%)  1/363 (0.28%) 
Bipolar disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Borderline personality disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Bruxism * 1  0/362 (0.00%)  1/363 (0.28%) 
Confusional state * 1  2/362 (0.55%)  0/363 (0.00%) 
Depressed mood * 1  0/362 (0.00%)  1/363 (0.28%) 
Depression * 1  11/362 (3.04%)  10/363 (2.75%) 
Disorientation * 1  0/362 (0.00%)  1/363 (0.28%) 
Initial insomnia * 1  0/362 (0.00%)  1/363 (0.28%) 
Insomnia * 1  12/362 (3.31%)  11/363 (3.03%) 
Irritability * 1  1/362 (0.28%)  2/363 (0.55%) 
Libido decreased * 1  1/362 (0.28%)  0/363 (0.00%) 
Listless * 1  1/362 (0.28%)  0/363 (0.00%) 
Loss of libido * 1  1/362 (0.28%)  0/363 (0.00%) 
Mood altered * 1  1/362 (0.28%)  1/363 (0.28%) 
Nervousness * 1  1/362 (0.28%)  0/363 (0.00%) 
Nicotine dependence * 1  0/362 (0.00%)  1/363 (0.28%) 
Nightmare * 1  2/362 (0.55%)  0/363 (0.00%) 
Panic attack * 1  1/362 (0.28%)  0/363 (0.00%) 
Restlessness * 1  1/362 (0.28%)  0/363 (0.00%) 
Sleep disorder * 1  4/362 (1.10%)  0/363 (0.00%) 
Stress * 1  0/362 (0.00%)  1/363 (0.28%) 
Substance abuse * 1  0/362 (0.00%)  1/363 (0.28%) 
Suicidal ideation * 1  0/362 (0.00%)  1/363 (0.28%) 
Tobacco abuse * 1  1/362 (0.28%)  0/363 (0.00%) 
Renal and urinary disorders     
Dysuria * 1  1/362 (0.28%)  7/363 (1.93%) 
Glycosuria * 1  0/362 (0.00%)  2/363 (0.55%) 
Haematuria * 1  2/362 (0.55%)  1/363 (0.28%) 
Micturition disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Micturition urgency * 1  0/362 (0.00%)  1/363 (0.28%) 
Nephrolithiasis * 1  0/362 (0.00%)  2/363 (0.55%) 
Nephroptosis * 1  1/362 (0.28%)  0/363 (0.00%) 
Polyuria * 1  1/362 (0.28%)  0/363 (0.00%) 
Proteinuria * 1  1/362 (0.28%)  3/363 (0.83%) 
Pyelocaliectasis * 1  1/362 (0.28%)  0/363 (0.00%) 
Renal colic * 1  1/362 (0.28%)  0/363 (0.00%) 
Renal failure * 1  0/362 (0.00%)  1/363 (0.28%) 
Renal haematoma * 1  0/362 (0.00%)  1/363 (0.28%) 
Renal impairment * 1  0/362 (0.00%)  1/363 (0.28%) 
Tubulointerstitial nephritis * 1  0/362 (0.00%)  1/363 (0.28%) 
Ureterolithiasis * 1  1/362 (0.28%)  0/363 (0.00%) 
Urethral discharge * 1  0/362 (0.00%)  1/363 (0.28%) 
Urethral pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Reproductive system and breast disorders     
Atrophic vulvovaginitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Balanoposthitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Cervical dysplasia * 1  0/362 (0.00%)  2/363 (0.55%) 
Dysmenorrhoea * 1  0/362 (0.00%)  1/363 (0.28%) 
Erectile dysfunction * 1  2/362 (0.55%)  2/363 (0.55%) 
Erection increased * 1  0/362 (0.00%)  1/363 (0.28%) 
Galactorrhoea * 1  1/362 (0.28%)  0/363 (0.00%) 
Genital burning sensation * 1  1/362 (0.28%)  0/363 (0.00%) 
Genital lesion * 1  1/362 (0.28%)  0/363 (0.00%) 
Menstruation irregular * 1  0/362 (0.00%)  1/363 (0.28%) 
Penile blister * 1  0/362 (0.00%)  1/363 (0.28%) 
Perineal disorder * 1  1/362 (0.28%)  0/363 (0.00%) 
Prostatitis * 1  0/362 (0.00%)  1/363 (0.28%) 
Vaginal haemorrhage * 1  0/362 (0.00%)  2/363 (0.55%) 
Vulvovaginal dryness * 1  0/362 (0.00%)  1/363 (0.28%) 
Vulvovaginal pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Respiratory, thoracic and mediastinal disorders     
Allergic sinusitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Asthma * 1  2/362 (0.55%)  3/363 (0.83%) 
Catarrh * 1  1/362 (0.28%)  1/363 (0.28%) 
Cough * 1  12/362 (3.31%)  11/363 (3.03%) 
Dysphonia * 1  1/362 (0.28%)  0/363 (0.00%) 
Dyspnoea * 1  2/362 (0.55%)  1/363 (0.28%) 
Dyspnoea exertional * 1  1/362 (0.28%)  1/363 (0.28%) 
Epistaxis * 1  1/362 (0.28%)  1/363 (0.28%) 
Haemoptysis * 1  1/362 (0.28%)  0/363 (0.00%) 
Nasal congestion * 1  1/362 (0.28%)  2/363 (0.55%) 
Oropharyngeal pain * 1  6/362 (1.66%)  9/363 (2.48%) 
Pharyngeal erythema * 1  1/362 (0.28%)  0/363 (0.00%) 
Pharyngeal inflammation * 1  1/362 (0.28%)  0/363 (0.00%) 
Productive cough * 1  2/362 (0.55%)  0/363 (0.00%) 
Respiratory disorder * 1  0/362 (0.00%)  1/363 (0.28%) 
Rhinitis allergic * 1  4/362 (1.10%)  2/363 (0.55%) 
Rhinorrhoea * 1  3/362 (0.83%)  2/363 (0.55%) 
Sinus congestion * 1  1/362 (0.28%)  3/363 (0.83%) 
Sinus pain * 1  0/362 (0.00%)  1/363 (0.28%) 
Sinus polyp * 1  0/362 (0.00%)  1/363 (0.28%) 
Sneezing * 1  0/362 (0.00%)  1/363 (0.28%) 
Tonsillar hypertrophy * 1  2/362 (0.55%)  0/363 (0.00%) 
Upper-airway cough syndrome * 1  1/362 (0.28%)  0/363 (0.00%) 
Wheezing * 1  1/362 (0.28%)  0/363 (0.00%) 
Skin and subcutaneous tissue disorders     
Acne * 1  8/362 (2.21%)  6/363 (1.65%) 
Alopecia * 1  1/362 (0.28%)  5/363 (1.38%) 
Blister * 1  0/362 (0.00%)  1/363 (0.28%) 
Dermal cyst * 1  1/362 (0.28%)  2/363 (0.55%) 
Dermatitis * 1  1/362 (0.28%)  2/363 (0.55%) 
Dermatitis acneiform * 1  1/362 (0.28%)  1/363 (0.28%) 
Dermatitis allergic * 1  2/362 (0.55%)  1/363 (0.28%) 
Dermatitis atopic * 1  1/362 (0.28%)  0/363 (0.00%) 
Dermatitis contact * 1  1/362 (0.28%)  1/363 (0.28%) 
Drug eruption * 1  0/362 (0.00%)  1/363 (0.28%) 
Dry skin * 1  4/362 (1.10%)  3/363 (0.83%) 
Eczema * 1  1/362 (0.28%)  4/363 (1.10%) 
Erythema * 1  6/362 (1.66%)  3/363 (0.83%) 
Hidradenitis * 1  1/362 (0.28%)  1/363 (0.28%) 
Hyperhidrosis * 1  1/362 (0.28%)  1/363 (0.28%) 
Intertrigo * 1  1/362 (0.28%)  1/363 (0.28%) 
Leukoplakia * 1  0/362 (0.00%)  1/363 (0.28%) 
Night sweats * 1  4/362 (1.10%)  2/363 (0.55%) 
Pain of skin * 1  0/362 (0.00%)  2/363 (0.55%) 
Papule * 1  0/362 (0.00%)  1/363 (0.28%) 
Penile ulceration * 1  1/362 (0.28%)  1/363 (0.28%) 
Photosensitivity reaction * 1  1/362 (0.28%)  1/363 (0.28%) 
Precancerous skin lesion * 1  1/362 (0.28%)  0/363 (0.00%) 
Prurigo * 1  0/362 (0.00%)  1/363 (0.28%) 
Pruritus * 1  9/362 (2.49%)  4/363 (1.10%) 
Pruritus generalised * 1  0/362 (0.00%)  1/363 (0.28%) 
Psoriasis * 1  1/362 (0.28%)  0/363 (0.00%) 
Rash * 1  32/362 (8.84%)  23/363 (6.34%) 
Rash erythematous * 1  1/362 (0.28%)  0/363 (0.00%) 
Rash generalised * 1  1/362 (0.28%)  2/363 (0.55%) 
Rash macular * 1  2/362 (0.55%)  4/363 (1.10%) 
Rash maculo-papular * 1  3/362 (0.83%)  2/363 (0.55%) 
Rash morbilliform * 1  0/362 (0.00%)  1/363 (0.28%) 
Rash papular * 1  3/362 (0.83%)  2/363 (0.55%) 
Rash pruritic * 1  2/362 (0.55%)  1/363 (0.28%) 
Scab * 1  0/362 (0.00%)  1/363 (0.28%) 
Seborrhoeic dermatitis * 1  6/362 (1.66%)  1/363 (0.28%) 
Skin burning sensation * 1  0/362 (0.00%)  1/363 (0.28%) 
Skin discolouration * 1  1/362 (0.28%)  0/363 (0.00%) 
Skin exfoliation * 1  0/362 (0.00%)  1/363 (0.28%) 
Skin lesion * 1  4/362 (1.10%)  2/363 (0.55%) 
Skin maceration * 1  1/362 (0.28%)  0/363 (0.00%) 
Skin mass * 1  0/362 (0.00%)  1/363 (0.28%) 
Skin ulcer * 1  0/362 (0.00%)  1/363 (0.28%) 
Solar dermatitis * 1  1/362 (0.28%)  0/363 (0.00%) 
Toxic skin eruption * 1  1/362 (0.28%)  0/363 (0.00%) 
Urticaria * 1  4/362 (1.10%)  3/363 (0.83%) 
Social circumstances     
Dental prosthesis user * 1  0/362 (0.00%)  1/363 (0.28%) 
Vascular disorders     
Hot flush * 1  1/362 (0.28%)  2/363 (0.55%) 
Hyperaemia * 1  1/362 (0.28%)  0/363 (0.00%) 
Hypertension * 1  6/362 (1.66%)  6/363 (1.65%) 
Hypotension * 1  0/362 (0.00%)  1/363 (0.28%) 
Orthostatic hypotension * 1  1/362 (0.28%)  0/363 (0.00%) 
Thrombosis * 1  1/362 (0.28%)  0/363 (0.00%) 
Varicose vein * 1  1/362 (0.28%)  0/363 (0.00%) 
1
Term from vocabulary, MedDRA Version 19.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior director, Medical leader
Organization: Janssen Sciences Ireland
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT02431247     History of Changes
Other Study ID Numbers: CR107277
TMC114FD2HTX3001 ( Other Identifier: Janssen Sciences Ireland UC )
2015-000754-38 ( EudraCT Number )
First Submitted: April 27, 2015
First Posted: April 30, 2015
Results First Submitted: August 15, 2018
Results First Posted: September 14, 2018
Last Update Posted: October 9, 2019