Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care (NCT NCT03227861)

Last Updated: 2025-02-04

Results Overview

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 a window of time, along with study drug discontinuation status. If HIV RNA level is \< 50 copies per mL at Week 48, it is considered as virologic success as per the snapshot approach.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

109 participants

Primary outcome timeframe

Week 48

Results posted on

2025-02-04

Participant Flow

Out of 97 participants who completed the main study, 80 participants continued into the extension phase and were treated with Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC).

Participant milestones

Participant milestones
Measure	D/C/F/TAF Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48. Participants who completed the Week 48 visit were given the opportunity to continue D/C/F/TAF treatment during the extension phase until the D/C/F/TAF FDC tablet became commercially available and was reimbursed, or could be accessed through another source, or until the sponsor terminated clinical development (Up to 96 Weeks).
Main Study Period (Week 0 to Week 48) STARTED	109
Main Study Period (Week 0 to Week 48) COMPLETED	97
Main Study Period (Week 0 to Week 48) NOT COMPLETED	12
Extension Period (Week 48 to Week 96) STARTED	80
Extension Period (Week 48 to Week 96) COMPLETED	0
Extension Period (Week 48 to Week 96) NOT COMPLETED	80

Reasons for withdrawal

Reasons for withdrawal
Measure	D/C/F/TAF Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48. Participants who completed the Week 48 visit were given the opportunity to continue D/C/F/TAF treatment during the extension phase until the D/C/F/TAF FDC tablet became commercially available and was reimbursed, or could be accessed through another source, or until the sponsor terminated clinical development (Up to 96 Weeks).
Main Study Period (Week 0 to Week 48) Lost to Follow-up	4
Main Study Period (Week 0 to Week 48) Withdrawal by Subject	1
Main Study Period (Week 0 to Week 48) Adverse Event	1
Main Study Period (Week 0 to Week 48) Protocol Violation	1
Main Study Period (Week 0 to Week 48) Other	5
Extension Period (Week 48 to Week 96) Transition to Commercial D/C/F/TAF	55
Extension Period (Week 48 to Week 96) Transition to Other ARV Treatment	16
Extension Period (Week 48 to Week 96) Lost to Follow-up	6
Extension Period (Week 48 to Week 96) Adverse Event	1
Extension Period (Week 48 to Week 96) Other	2

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	D/C/F/TAF n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Age, Continuous	32.5 years STANDARD_DEVIATION 12.02 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	35 Participants n=5 Participants
Race (NIH/OMB) White	65 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	109 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: 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.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies/mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach	84.4 Percentage of participants Interval 76.44 to 90.03

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 24, 36, and 48

Population: The ITT analysis set included all participants who were randomized and received at least one dose of study treatment in study. Here, n (number analyzed) signifies participants analyzed for this outcome measure (OM) at specified timepoints.

Change from baseline in log10 HIV-1 RNA viral load (\<50/200 copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 were reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 2	-1.65 log10 HIV-1 RNA copies per mL Standard Error 0.056
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 4	-2.02 log10 HIV-1 RNA copies per mL Standard Error 0.066
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 8	-2.43 log10 HIV-1 RNA copies per mL Standard Error 0.086
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 12	-2.78 log10 HIV-1 RNA copies per mL Standard Error 0.080
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 24	-3.08 log10 HIV-1 RNA copies per mL Standard Error 0.096
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 36	-3.14 log10 HIV-1 RNA copies per mL Standard Error 0.102
Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 Change at Week 48	-3.14 log10 HIV-1 RNA copies per mL Standard Error 0.099

SECONDARY outcome

Timeframe: Week 24

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Percentage of participants with HIV-1 RNA \< 50 copies/mL were reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	81.7 Percentage of Participants Interval 73.35 to 87.8

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24 and 48

Population: 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 analyzed) signifies participants analyzed for this OM at specified timepoints.

The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Weeks 12, 24 and 48 were assessed.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 12, 24 and 48 Change at Week 12	149.56 Cells per millimeter cube (cells/mm^3) Standard Error 16.621
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 12, 24 and 48 Change at Week 24	182.11 Cells per millimeter cube (cells/mm^3) Standard Error 16.885
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 12, 24 and 48 Change at Week 48	222.60 Cells per millimeter cube (cells/mm^3) Standard Error 20.618

SECONDARY outcome

Timeframe: Up to Week 48

Population: The safety analysis was performed on the ITT analysis set which included all enrolled participants who received at least 1 dose of study treatment.

Number of participants that required discontinuation after enrollment based on safety stopping rules were reported. Stopping rules include the following reasons: a). Estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) formula \< 50 milliliter per minute (mL/min) b). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to (\>=) 2.5\*upper limit of normal (ULN); c). Serum lipase \>=1.5\*ULN; d). Positive serum human chorionic gonadotropin pregnancy test (beta-hCG) for women of childbearing potential; e). Laboratory results that the investigator believes should result in discontinuation of study medication; f). Participants identified with active hepatitis C virus (HCV) infection that in the opinion of the investigator requires HCV treatment immediately or expected to be needed during the course of the study with agents not compatible with D/C/F/TAF FDC.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Number of Participants That Required Discontinuation After Enrollment Based on Safety Stopping Rules	3 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The safety analysis was performed on the ITT analysis set which included all enrolled participants who received at least 1 dose of study treatment.

Percentage of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs)	0.9 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The safety analysis was performed on the ITT analysis set which included all enrolled participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Grade 3	11.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Grade 4	0.9 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The safety analysis was performed on the ITT analysis set which included all enrolled participants who received at least 1 dose of study treatment.

Percentage of participants experiencing grade 3 and 4 laboratory abnormalities was assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities ALT: Grade 3	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities ALT: Grade 4	2.8 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities AST: Grade 3	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities AST: Grade 4	3.7 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Calcium: Grade 3	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Calcium: Grade 4	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Glucose: Grade 3	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Glucose: Grade 4	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Hyperbilirubinemia: Grade 3	2.8 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Hyperbilirubinemia: Grade 4	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Hypophosphatemia: Grade 3	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Hypophosphatemia: Grade 4	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Sodium: Grade 3	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Sodium: Grade 4	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Absolute Lymphocytes Count: Grade 3	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Absolute Lymphocytes Count: Grade 4	0.9 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Platelet Count: Grade 3	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Platelet Count: Grade 4	0.9 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 35

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Percentage of participants meeting resistance stopping rules, requiring discontinuation of study treatment due to baseline resistance findings were reported. Investigator reviewed antiretroviral screening/baseline resistance data at Week 4, depending on availability of screening/baseline HIV genotypic drug resistance testing results from central laboratory. Participants who do not show full sensitivity to all drugs in the fixed-dose combination (FDC) study regimen according to the susceptibility assessment in the Genosure Prime report will be contacted to return to study site for early study treatment discontinuation (ESTD). Participants with identified resistance to lamivudine/Emtricitabine, attributed to the presence of the M184I/V mutation alone will be permitted to remain in the study.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Meeting Resistance Stopping Rules, Requiring Discontinuation of Study Treatment Due to Baseline Resistance Findings	0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: 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 participants evaluated for this endpoint.

Percentage of Participants with resistance-associated mutations present at baseline were reported and included mutations in the domain of PR, RT (including nucleoside reverse transcriptase inhibitor \[NRTIs\] and non-nucleoside/nucleotide reverse transcriptase inhibitor \[NNRTIs\]), INI, RAMs as determined by the GenoSure Prime assay. Genotypes were not available for 7 participants due to failed amplification of viral deoxyribo nucleic acid (DNA) (that is, low viral load (VL) \[\<500 copies/mL\], reduced viral fitness, compromised sample collection/handling, primer incompatibility).

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=102 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Emtricitabine RAM	2.0 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Primary PI RAM	4.9 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Secondary PI RAM	98.0 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Darunavir RAM	0 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) NNRTI RAM	27.5 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Primary INI RAM	0 Percentage of Participants
Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) Secondary INI RAM	4.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 24 and 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA \<1 log10 reduction from baseline, and HIV-1 RNA \>= 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA \<50 copies/mL, a rebound in HIV 1 RNA to \>= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a \>1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 24 and 48 Week 24	0 Percentage of participants
Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 24 and 48 Week 48	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Percentage of participants developing RAMs and loss of phenotypic susceptibility, upon meeting PDVF were reported. Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA \<1 log10 reduction from baseline, and HIV-1 RNA greater than or equal to (\>=) 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA \<50 copies/mL, a rebound in HIV 1 RNA to \>= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a \>1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Developing Resistance-associated Mutation (RAMs) and Loss of Phenotypic Susceptibility, Upon Meeting Protocol-defined Virologic Failure (PDVF)	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Percentage of participants lost-to-follow-up throughout the 48 Weeks of treatment were reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Lost-to-Follow-up Throughout the 48 Weeks of Treatment	3.67 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The modified ITT analysis set included all participants who were randomized and received at least one dose of study treatment and are HIV-1 positive after enrollment. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM. Here, n (number analyzed) signifies participants analyzed at specified categories.

Percentage of participants with retention in care completed and with documented clinical visit (within 90 days of discontinuation) were reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=11 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Retention in Care Completed and With Documented Clinical Visit Retention in care: Completed	63.6 Percentage of participants
Percentage of Participants With Retention in Care Completed and With Documented Clinical Visit Documented Clinical Visit	85.7 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 24, 36, and 48

Percentage of participants with treatment adherence \>95% based on pill count at Weeks 4, 8, 12, 24, 36, and 48 were reported. Treatment adherence was defined as having a treatment adherence of greater than (\>) 95 percent (%) by pill count.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 12	79.4 Percentage of participants
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 4	83.5 Percentage of participants
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 8	84.5 Percentage of participants
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 24	76.5 Percentage of participants
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 36	75.8 Percentage of participants
Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 >95% at Week 48	65.6 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 24, 36, and 48

Percentage of participants with 100 % adherence based on participants self-report, using a 4-Day recall at Weeks 4, 8, 12, 24, 36, and 48 was reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 4	99.76 Percentage of participants Standard Deviation 2.440
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 8	99.50 Percentage of participants Standard Deviation 3.518
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 12	99.02 Percentage of participants Standard Deviation 6.967
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 24	98.04 Percentage of participants Standard Deviation 10.949
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 36	99.49 Percentage of participants Standard Deviation 3.535
Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 Week 48	99.48 Percentage of participants Standard Deviation 3.571

SECONDARY outcome

Timeframe: Weeks 4, 24, and 48

The HIV treatment satisfaction questionnaire (HIVTSQ) is based on a 10-item self-reported scale that measures overall satisfaction with treatment. The HIVTSQ items are summed up to produce a treatment satisfaction score (0 to 60) and an individual satisfaction rating for each item (0 to 6). The higher the score, the greater the treatment satisfaction.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Mean Total Scores for the HIV-Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4, 24, and 48 Week 4	56.52 Units on a scale Standard Error 0.472
Mean Total Scores for the HIV-Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4, 24, and 48 Week 24	57.87 Units on a scale Standard Error 0.387
Mean Total Scores for the HIV-Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4, 24, and 48 Week 48	57.88 Units on a scale Standard Error 0.442

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Number of participants with hospitalizations (overnight) was reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Number of Participants With Hospitalizations	11 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Duration of hospitalizations in days was reported for those participants hospitalized during the course of the study. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this OM.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=11 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Duration of Hospitalizations	5.0 Days Interval 1.0 to 15.0

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Number of participants with outpatient visits (in addition to study visits, including General practitioner visit, Specialist visit, Nurse practitioner visit, Physician assistant visit, Home healthcare nurse visit and Other visit) was reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Number of Participants With Outpatient Visits General practitioner visit	33 Participants
Number of Participants With Outpatient Visits Specialist visit	28 Participants
Number of Participants With Outpatient Visits Nurse practitioner visit	16 Participants
Number of Participants With Outpatient Visits Physician assistant visit	6 Participants
Number of Participants With Outpatient Visits Home healthcare nurse visit	0 Participants
Number of Participants With Outpatient Visits Other visit	25 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

Number of participants with emergency room visits was reported.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Number of Participants With Emergency Room Visits	19 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: 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 analyzed) signifies those participants who were evaluable for the specified categories.

Median medical costs of care (United States of America \[USA\] dollars) based on healthcare resource utilization \[HRU\]) were reported. The cost of care specified for overnight hospitalization, hospital day care ward (without overnight), emergency room visit, general practitioner visit, specialist visit, nurse practitioner visit, physician assistant visit and Other visit.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=109 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Other visit	148.0 USA dollars Interval 16.0 to 788.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Overnight hospitalization	2035.0 USA dollars Interval 2035.0 to 4070.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Hospital day care ward (without overnight)	341.0 USA dollars Interval 341.0 to 341.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Emergency room visit	212.0 USA dollars Interval 212.0 to 424.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) General practitioner visit	142.0 USA dollars Interval 71.0 to 355.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Specialist visit	94.0 USA dollars Interval 94.0 to 752.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Nurse practitioner visit	66.0 USA dollars Interval 66.0 to 264.0
Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) Physician assistant visit	47.0 USA dollars Interval 47.0 to 94.0

SECONDARY outcome

Timeframe: Up to Week 96

Population: Safety analysis set (SAS) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug up to extension phase.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=80 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs) Through Week 96	1.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 96

Population: Safety analysis set (SAS) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug up to extension phase.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=80 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Through Week 96 Grade 3	7.5 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Through Week 96 Grade 4	2.5 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 96

Population: Safety analysis set (SAS) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug up to extension phase.

Percentage of participants experiencing grade 3 and 4 laboratory abnormalities were assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=80 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96 Glucose: Grade 3	2.5 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96 Glucose: Grade 4	0 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96 Hypophosphatemia: Grade 3	1.3 Percentage of participants
Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96 Hypophosphatemia: Grade 4	0 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 72 and 96

Population: Safety analysis set (SAS) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug up to extension phase. Here 'n' (number analyzed) signifies number of participants with observed virologic response at specified timepoints.

Outcome measures

Outcome measures
Measure	D/C/F/TAF: Main Study n=80 Participants Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.
Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 72 and 96 Week 72	10.6 Percentage of participants
Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 72 and 96 Week 96	9.1 Percentage of participants

Adverse Events

D/C/F/TAF: Main Study

Serious events: 10 serious events

Other events: 92 other events

Deaths: 0 deaths

D/C/F/TAF: Extension Study

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior director medical leader

Janssen Scientific Affairs, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	D/C/F/TAF: Main Study n=109 participants at risk Participants received oral tablet containing Darunavir 800 milligram (mg)/Cobicistat 150 mg/Emtricitabine 200 mg/Tenofovir alafenamide 10 mg (D/C/F/TAF) as Fixed-dose Combination (FDC) from Day 1 to Week 48.	D/C/F/TAF: Extension Study n=80 participants at risk Participants who completed the Week 48 visit were given the opportunity to continue D/C/F/TAF treatment during the extension phase until the D/C/F/TAF FDC tablet became commercially available and was reimbursed, or could be accessed through another source, or until the sponsor terminated clinical development (Up to 96 Weeks).
Gastrointestinal disorders Colitis	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Gastrointestinal disorders Pancreatitis Acute	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Infections and infestations Appendicitis	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Infections and infestations Cellulitis	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Infections and infestations Gastroenteritis	0.00% 0/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Infections and infestations Pneumonia	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Injury, poisoning and procedural complications Abdominal Injury	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	1.2% 1/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Injury, poisoning and procedural complications Muscle Rupture	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	1.2% 1/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Injury, poisoning and procedural complications Road Traffic Accident	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Nervous system disorders Seizure	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Psychiatric disorders Mania	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Psychiatric disorders Psychotic Disorder	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Psychiatric disorders Suicidal Ideation	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	1.2% 1/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.92% 1/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	0.00% 0/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Infections and infestations Meningitis aseptic	0.00% 0/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	1.2% 1/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.
Injury, poisoning and procedural complications Head injury	0.00% 0/109 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.	1.2% 1/80 • Main study: Up to 48 Weeks; Extension Study: Up to 96 Weeks The safety analysis was performed on the Intent-to-treat analysis set (ITT) analysis set during main study (Week 0-48) included all the participants who were randomized and received at least one dose of study treatment in the study and safety analysis set (SAS) was used for the analyses during the extension study (Week 48-96) included all participants who received at least 1 dose of study drug and contributed any safety data after the start of study drug.