Download PDF

Clinical Trial Results:
A Phase IIb Study Evaluating a Long-Acting Intramuscular Regimen of GSK1265744 plus TMC278 For The Maintenance of Virologic Suppression Following an Induction of Virologic Suppression on an Oral regimen of GSK1265744 plus Abacavir/Lamivudine in HIV-1 Infected, Antiretroviral Therapy-Naive Adult Subjects

Summary
EudraCT number	2013-000783-29
Trial protocol	DE ES
Global end of trial date	20 Apr 2023

Results information
Results version number	v3(current)
This version publication date	17 Jul 2024
First version publication date	23 Apr 2016
Other versions	v1 , v2
Version creation reason	Correction of full data set Full data set corrected based on final review.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

200056

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

ViiV Healthcare

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Jun 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

To select an intramuscular dosing regimen of GSK744 LA plus TMC278 LA based on a comparison of the Week 32 antiviral activity, tolerability, and safety of two IM dosing regimens, relative to GSK744 30 mg plus Abacavir/Lamivudine (ABC/3TC) orally once daily.

Protection of trial subjects

An IDMC committee will evaluate the efficacy, tolerability, and safety of cabotegravir (CAB) and Rilpivirine (RPV) at the following times: before all eligible subjects have transitioned from the Induction Period to the Maintenance Period; after approximately 45 subjects have reached Week 8 of the Maintenance Period. Futility guidance (e.g., a Bayesian posterior probability approach when 50% of subjects have completed Week 24 of the Maintenance Period) is included to monitor the performance of all treatment arms in order to prevent subjects from continuing on a dosing regimen if existing data indicates that subjects are at unacceptable risk of inadequate maintenance of virologic suppression. A CAB treatment arm should be recommended to stop if there is an indication of any safety signal/effect that would not support continuation of one or more of the CAB treatment groups. This should take into consideration any of the following which are felt to be clinically significant: I. Serious adverse events (e.g. liver event). II. Combinations of non-serious events. III. Treatment-limiting adverse events. IV. Unacceptable number of protocol defined virologic failures with CAB or RPV resistance defined as at least 3 or more virologic failures comprising of ≥ 20% of the treated subjects in an IM treatment arm. V. Mean predose concentrations for the long acting (LA) treatment arm less than 1x protein-adjusted 90% inhibitory concentration (PAIC) 90 (0.166 µg/mL) for CAB and less than 12ng/mL for RPV.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Apr 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 83

Country: Number of subjects enrolled

Canada: 33

Country: Number of subjects enrolled

Spain: 105

Country: Number of subjects enrolled

France: 36

Country: Number of subjects enrolled

Germany: 52

Worldwide total number of subjects

309

EEA total number of subjects

193

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

309

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted across 50 sites in five countries (United States, Canada, France, Germany and Spain). The results presented are based on final analysis, up to approximately Week 468.

Screening details

Study consisted of 28 days Screening Period, 20 weeks Induction Period, 96 weeks Maintenance Period (MP), Extension Period (EP) and 52 weeks Long-Term Follow Up Period (LTFP). A total of 309 participants were enrolled in the study and entered the Induction Period, of which 288 completed and 286 were qualified and randomized into the MP.

Period 1 title

Induction Period (20 Weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

CAB 30 mg+ABC/3TC QD (Induction Period)

Arm description

In induction period, all participants received an oral regimen of cabotegravir (CAB) 30 milligrams (mg) once daily (QD) plus abacavir/lamivudine (ABC/3TC) 600/300 mg QD for 20 weeks. They also received an oral dose of Rilpivirine (RPV) 25 mg tablet once daily in the last 4 weeks of the Induction Period.

Arm type

Experimental

Investigational medicinal product name

Cabotegravir Oral Tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Cabotegravir (CAB) Oral Tablet was formulated as white to almost white oval shaped film coated 30 mg tablets for oral administration. In IP, participants received CAB 30 mg once daily for 20 weeks

Investigational medicinal product name

Abacavir/Lamivudine Oral Tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Abacavir/Lamivudine (ABC/3TC)was supplied as fixed dose combination (FDC) oral tablet, which contained 600 mg of ABC (as abacavir sulfate) and 300 mg of 3TC. The tablets were orange, film-coated, modified capsule-shaped and debossed with "GS FC2" on one side with no markings on the reverse side. ABC/3TC was packaged in bottles of 30 tablets. In IP, participants received ABC/3TC 600/300 mg once daily for 20 weeks.

Investigational medicinal product name

Rilpivirine Oral Tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Rilpivirine (RPV) Oral Tablet was supplied as a 25 mg tablet that was off-white, round, biconvex, film-coated and debossed on one side with “TMC” and the other side with “25”. Participants received RPV 25 mg tablet once daily in last 4 weeks of IP.

Number of subjects in period 1	CAB 30 mg+ABC/3TC QD (Induction Period)
Started	309
Completed	288
Not completed	21
Consent withdrawn by subject	5
Physician decision	1
Adverse event, non-fatal	3
Lost to follow-up	2
Met protocol-defined stopping criteria	3
Lack of efficacy	5
Protocol deviation	2

Period 2 title

Maintenance Period (Up to Week 96)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)

Arm description

On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive following intramuscular (IM) doses: Day 1 only: CAB long acting (LA) 800 mg (loading dose delivered as two 400 mg IM injections) + RPV LA 900 mg IM; Week 4 only: CAB LA 600 mg IM (second loading dose, no RPV); and from Week 8: CAB LA 600 mg IM +RPV LA 900 mg IM every 8 Weeks (Q8W) for 96 weeks. Eligible participants had the option to continue study participation in the Extension Period.

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Rilpivirine Injectable Suspension was a sterile white suspension containing 300 mg/mL of TMC278 as free base for administration by intramuscular (IM) injection. The product was packaged in a 2 mL USP Type I glass vial with a 13 mm grey stopper and aluminium seal. Each vial was for single use containing a nominal fill of 2.0 mL, and did not require dilution prior to administration but required refrigeration. Participants randomized to Q8W regimen arm received following intra muscular (IM) doses: RPV LA 900 mg IM every 8 Weeks (Q8W) for 96 weeks

Investigational medicinal product name

Cabotegravir Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

CAB Injectable Suspension was a sterile white to slightly colored suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. The product was packaged in a 3 mL United States Pharmacopeia (USP) Type I glass vial with a 13 mm gray stopper and aluminium seal. Each vial was for single use containing a withdrawable volume of 2.0 mL, and did not require dilution prior to administration. Participants randomized to Q8W regimen arm received following intra muscular (IM) doses: Day 1 only – CAB LA 800 mg (loading dose delivered as two 400 mg IM injections). Week 4 only - CAB LA 600 mg IM. Week 8 - CAB LA 600 mg IM every 8 Weeks (Q8W) for 96 weeks.

CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)

Arm description

On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive following IM doses: Day 1 only: CAB LA 800 mg (loading dose delivered as two 400 mg IM injections) + RPV LA 600 mg IM; and from Week 4: CAB LA 400 mg IM + RPV LA 600 mg IM every 4 Weeks (Q4W) for 96 weeks. Eligible participants had the option to continue study participation in the Extension Period.

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Rilpivirine Injectable Suspension was a sterile white suspension containing 300 mg/mL of TMC278 as free base for administration by intramuscular (IM) injection. The product was packaged in a 2 mL USP Type I glass vial with a 13 mm grey stopper and aluminium seal. Each vial was for single use containing a nominal fill of 2.0 mL, and did not require dilution prior to administration but required refrigeration. Participants randomized to Q4W regimen arm received following IM doses: RPV LA 600 mg IM every 4 weeks (Q4W) for 96 weeks.

Investigational medicinal product name

Cabotegravir Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

CAB Injectable Suspension was a sterile white to slightly colored suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. The product was packaged in a 3 mL USP Type I glass vial with a 13 mm gray stopper and aluminium seal. Each vial was for single use containing a withdrawable volume of 2.0 mL, and did not require dilution prior to administration. Participants randomized to Q4W regimen arm received following IM doses: Day 1 only - CAB LA 800 mg (loading dose delivered as two 400 mg IM injections). Week 4 - CAB LA 400 mg IM + every 4 weeks (Q4W) for 96 weeks

CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)

Arm description

On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive CAB and ABC/3TC QD for 96 weeks. Eligible participants had the option to continue study participation in Extension Period by switching to an optimized IM CAB LA+ RPV LA regimen of their choice (Q8W or Q4W).

Arm type

Experimental

Investigational medicinal product name

Abacavir/Lamivudine Oral Tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Cabotegravir Oral Tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Cabotegravir (CAB) Oral Tablet was formulated as white to almost white oval shaped film coated 30 mg tablets for oral administration. In IP, participants received CAB 30 mg once daily for 20 weeks

Number of subjects in period 2 ^[1]	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Started	115	115	56
Completed	110	101	47
Not completed	5	14	9
Consent withdrawn by subject	1	3	5
Physician decision	1	-	-
Adverse event, non-fatal	1	8	1
Met protocol-defined stopping criteria	-	1	1
Lost to follow-up	-	-	1
Lack of efficacy	1	-	1
Protocol deviation	1	2	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 2 participants did not enter Maintenance phase as they had Day 1 viral loads >50 copies/milliliter.

Period 3 title

Extension Period (Week 97 to Study End)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension )

Arm description

Participants who completed 96 weeks of CAB 30 mg + ABC/3TC QD regimen in Maintenance Period transitioned to Extension Period and received an optimized loading dose of CAB LA 600 mg+RPV LA 900 mg IM at Week 100 and Week 104 followed by CAB LA 600 mg+RPV LA 900 mg IM-Q8W in the Extension Phase. Participants were followed up until end of Extension Period.

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Cabotegravir Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)

Arm description

Participants who completed 96 weeks of CAB 30 mg + ABC/3TC QD regimen in Maintenance Period transitioned to Extension Period and received an optimized loading dose of CAB LA 400 mg+RPV LA 900 mg IM at Week 100 followed by CAB LA 400 mg+RPV LA 900 mg IM-Q8W in the Extension Phase. Participants were followed up until end of Extension Period.

Arm type

Experimental

Investigational medicinal product name

Rilpivirine Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Cabotegravir Injectable Suspension

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 3 ^[2]	Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension )	Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)
Started	34	10
Completed	26	8
Not completed	8	2
Consent withdrawn by subject	2	-
Adverse event, non-fatal	2	1
Site closed	-	1
Lost to follow-up	1	-
Lack of efficacy	1	-
Protocol deviation	2	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only the eligible participants had the option to continue study participation in Extension Period by switching to an optimized IM CAB LA+ RPV LA regimen of their choice (Q8W or Q4W), hence a part of participants were excluded from this period.

Period 4 title

Long-Term Follow-up Period (52 weeks)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Long-Term Follow-Up Group

Arm description

This group included participants that were withdrawn from CAB LA+RPV LA IM regimens based on protocol criteria and were required to access Highly Active Antiretroviral Therapy (HAART) of choice. Participants were followed up for approximately 52 weeks. Due to system limitation: 43 participants transitioned in this group and accessed a HAART of choice.

Arm type

Experimental

Investigational medicinal product name

HAART

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection, Injection, Tablet

Routes of administration

Intramuscular use, Intramuscular use, Oral use

Dosage and administration details

Higly-active antiretroviral therapy chosen by participant based on investigator recommendations and based on availability.

Number of subjects in period 4	Long-Term Follow-Up Group
Started	34
Completed	34

Baseline characteristics

Top of page

Reporting group title

CAB 30 mg+ABC/3TC QD (Induction Period)

Reporting group description

Reporting group values	CAB 30 mg+ABC/3TC QD (Induction Period)	Total
Number of subjects	309	309
Age categorical
Units: Subjects
Adults (18-64 years)	309	309
Age Continuous
Units: Years
arithmetic mean (standard deviation)	36.6 ( 10.39 )	-
Sex: Female, Male
Units: Participants
Female	27	27
Male	282	282
Race/Ethnicity, Customized
Units: Subjects
African American/African Heritage	46	46
American Indian or Alaskan Native	10	10
Asian - Central/South Asian Heritage	1	1
Asian - Japanese Heritage	1	1
Asian - South East Asian Heritage	2	2
Native Hawaiian or Other Pacific Islander	1	1
White - Arabic/North African Heritage	6	6
White - White/Caucasian/European Heritage	240	240
Mixed Race	2	2

Subject analysis set title

CAB 30 mg+ABC/3TC QD

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis sets values	CAB 30 mg+ABC/3TC QD
Number of subjects	309
Age categorical
Units: Subjects
Adults (18-64 years)	309
Age Continuous
Units: Years
arithmetic mean (standard deviation)	36.6 ( 10.39 )
Sex: Female, Male
Units: Participants
Female	27
Male	282
Race/Ethnicity, Customized
Units: Subjects
African American/African Heritage	46
American Indian or Alaskan Native	10
Asian - Central/South Asian Heritage	1
Asian - Japanese Heritage	1
Asian - South East Asian Heritage	2
Native Hawaiian or Other Pacific Islander	1
White - Arabic/North African Heritage	6
White - White/Caucasian/European Heritage	240
Mixed Race	2

End points

Top of page

Reporting group title

CAB 30 mg+ABC/3TC QD (Induction Period)

Reporting group description

Reporting group title

CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)

Reporting group description

Reporting group title

CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)

Reporting group description

Reporting group title

CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)

Reporting group description

Reporting group title

Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension )

Reporting group description

Reporting group title

Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)

Reporting group description

Reporting group title

Long-Term Follow-Up Group

Reporting group description

Subject analysis set title

CAB 30 mg+ABC/3TC QD

Subject analysis set type

Intention-to-treat

Subject analysis set description

Primary: Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) level below 50 copies/milliliter (c/mL) at Week 32

Top of page

End point title

Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) level below 50 copies/milliliter (c/mL) at Week 32

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest as non-responders. The Intent-to-Treat Maintenance Exposed (ITT-ME) Population consisted of all randomized participants who received at least one injection or one dose of investigational product during the Maintenance Period of the study (on or after Day 1 visit).

End point type

Primary

End point timeframe

Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Percentage of participants	95	94	91

Statistical analysis 1

Comparison groups

CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension) v CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in Percentage

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

12.2

Statistical analysis 2

Comparison groups

CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension) v CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)

Number of subjects included in analysis

171

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in Percentage

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

11.5

Primary: Number of participants with protocol defined virologic failure (PDVF) until Week 32

Top of page

End point title

Number of participants with protocol defined virologic failure (PDVF) until Week 32 ^[1]

End point description

Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than 1.0 logarithm to base 10 (log10) c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL.

End point type

Primary

End point timeframe

Up to Week 32

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants	1	0	1

No statistical analyses for this end point

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Induction Period)

Top of page

End point title

Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Induction Period) ^[2]

End point description

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical intervention, drug-induced liver injury with hyperbilirubinaemia.

End point type

Primary

End point timeframe

Up to 20 weeks

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Participants
Any non-SAE	246
Any SAE	8

No statistical analyses for this end point

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Maintenance Period)

Top of page

End point title

Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Maintenance Period) ^[3]

End point description

End point type

Primary

End point timeframe

Up to an average of 59 weeks

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Any non-SAE	115	113	52
Any SAE	9	8	5

No statistical analyses for this end point

Primary: Number of participants with post-Baseline adverse events by maximum toxicity Grade

Top of page

End point title

Number of participants with post-Baseline adverse events by maximum toxicity Grade ^[4]

End point description

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with post-Baseline adverse events by maximum toxicity Grade have been presented.

End point type

Primary

End point timeframe

Up to an average of 59 weeks

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Any AE with maximum toxicity Grade 1	31	25	19
Any AE with maximum toxicity Grade 2	67	72	29
Any AE with maximum toxicity Grade 3	15	14	3
Any AE with maximum toxicity Grade 4	2	2	1

No statistical analyses for this end point

Primary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters

Top of page

End point title

Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters ^[5]

End point description

Clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), carbon dioxide(CO2) content/bicarbonate (HCO3), cholesterol, creatine kinase (CK), glucose, low density lipoprotein (LDL) cholesterol, lipase, potassium, and sodium, total bilirubin (TBIL) and triglycerides were evaluated. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the chemistry parameters have been presented.

End point type

Primary

End point timeframe

Up to an average of 59 weeks

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Maximum toxicity Grade 1	94	94	44
Maximum toxicity Grade 2	50	42	16
Maximum toxicity Grade 3	15	20	10
Maximum toxicity Grade 4	10	7	2

No statistical analyses for this end point

Primary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters

Top of page

End point title

Number of participants with maximum post-Baseline emergent toxicities for hematology parameters ^[6]

End point description

Hematology parameters hemoglobin, platelet count, total neutrophils and white blood cell count were evaluated. Toxicity was graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the hematology parameters have been presented.

End point type

Primary

End point timeframe

Up to an average of 59 weeks

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Maximum toxicity Grade 1	23	17	7
Maximum toxicity Grade 2	2	4	2
Maximum toxicity Grade 3	0	0	2
Maximum toxicity Grade 4	0	3	0

No statistical analyses for this end point

Primary: Number of participants with post-Baseline urinalysis dipstick results

Top of page

End point title

Number of participants with post-Baseline urinalysis dipstick results ^[7]

End point description

Urinalysis dipstick included urine occult blood, urine glucose, urine ketones, urine nitrite, urine protein and urine leukocyte. The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as positive, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample. Data presented includes all post-baseline dipstick results during Induction and Maintenance Periods, as well as LTFP for those participants who did not enter the extension period.

End point type

Primary

End point timeframe

Up to an average of 59 weeks

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was descriptive, hence no statistical analysis was performed.

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	20	20	10
Units: Participants
Urine Occult Blood, Trace, n=10,11,4	5	6	1
Urine Occult Blood, 1+, n=10,11,4	3	3	2
Urine Occult Blood, 2+, n=10,11,4	0	0	0
Urine Occult Blood, 3+, n=10,11,4	2	2	1
Urine Occult Blood, Positive, n=10,11,4	0	0	0
Urine Glucose, Trace, n=1,1,1	1	0	0
Urine Glucose, 1+, n=1,1,1	0	0	1
Urine Glucose, 2+, n=1,1,1	0	1	0
Urine Glucose, 3+, n=1,1,1	0	0	0
Urine Glucose, Positive, n=1,1,1	0	0	0
Urine Ketones, Trace, n=16,20,10	12	17	8
Urine Ketones, 1+, n=16,20,10	4	3	2
Urine Ketones, 2+, n=16,20,10	0	0	0
Urine Ketones, 3+, n=16,20,10	0	0	0
Urine Ketones, Positive, n=16,20,10	0	0	0
Urine Nitrite, Trace, n=1,3,1	0	0	0
Urine Nitrite, 1+, n=1,3,1	0	0	0
Urine Nitrite, 2+, n=1,3,1	0	0	0
Urine Nitrite, 3+, n=1,3,1	0	0	0
Urine Nitrite, Positive, n=1,3,1	1	3	1
Urine Protein, Trace, n=17,17,7	15	11	2
Urine Protein, 1+, n=17,17,7	2	4	5
Urine Protein, 2+, n=17,17,7	0	2	0
Urine Protein, 3+, n=17,17,7	0	0	0
Urine Protein, Positive, n=17,17,7	0	0	0
Urine Leukocyte, Trace, n=20,20,8	0	0	0
Urine Leukocyte, 1+, n=20,20,8	7	8	3
Urine Leukocyte, 2+, n=20,20,8	4	0	1
Urine Leukocyte, 3+, n=20,20,8	1	2	1
Urine Leukocyte, Positive, n=20,20,8	0	0	0

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Percentage of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Percentage of participants with HIV-1 RNA <200 c/mL and <50 c/mL for oral dose of CAB 30 mg plus ABC/3TC during Induction Period was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders. The Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of investigational product.

End point type

Secondary

End point timeframe

Week -20, Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Percentage of participants
HIV-1 RNA<50 c/mL, Week -20	0
HIV-1 RNA<50 c/mL, Week -16	72
HIV-1 RNA<50 c/mL, Week -12	90
HIV-1 RNA<50 c/mL, Week -8	89
HIV-1 RNA<50 c/mL, Week -4	92
HIV-1 RNA<50 c/mL, Day 1	91
HIV-1 RNA<200 c/mL, Week -20	0
HIV-1 RNA<200 c/mL, Week -16	94
HIV-1 RNA<200 c/mL, Week -12	97
HIV-1 RNA<200 c/mL, Week -8	96
HIV-1 RNA<200 c/mL, Week -4	94
HIV-1 RNA<200 c/mL, Day 1	94

No statistical analyses for this end point

Secondary: Absolute values of plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Absolute values of plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Plasma samples for quantitative HIV-1 RNA were collected at indicated time points. Log10 values for HIV-1 RNA have been presented.

End point type

Secondary

End point timeframe

Week -20, Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Log10 copies per milliliter
arithmetic mean (standard deviation)
Week -20, n=309	4.43 ( 0.672 )
Week -16, n=304	1.71 ( 0.229 )
Week -12, n=302	1.62 ( 0.108 )
Week -8, n=299	1.63 ( 0.281 )
Week -4, n=294	1.61 ( 0.080 )
Day 1, n=291	1.60 ( 0.070 )

No statistical analyses for this end point

Secondary: Change from Baseline in plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Change from Baseline in plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Plasma samples for quantitative HIV-1 RNA were collected at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as: HIV-1 RNA(log 10) at post-baseline visit minus HIV-1 RNA(log 10) at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: Log10 copies per milliliter
arithmetic mean (standard deviation)
Week -16, n=304	-2.72 ( 0.572 )
Week -12, n=302	-2.80 ( 0.640 )
Week -8, n=299	-2.79 ( 0.665 )
Week -4, n=294	-2.81 ( 0.647 )
Day 1, n=291	-2.82 ( 0.645 )

No statistical analyses for this end point

Secondary: Absolute values of cluster of differentiation 4+ (CD4+), for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Absolute values of cluster of differentiation 4+ (CD4+), for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Blood samples were collected at specified time points to assess CD4+ using flow cytometry. Mean and standard deviation values for CD4+ are presented.

End point type

Secondary

End point timeframe

Week -20, Week -16, Week -12, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Cells per cubic millimeter
arithmetic mean (standard deviation)
Week -20, n=309	498.9 ( 180.67 )
Week -16, n=304	630.5 ( 235.09 )
Week -12, n=300	664.2 ( 256.57 )
Week -4, n=292	702.3 ( 269.60 )
Day 1, n=291	690.9 ( 261.63 )

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Change from Baseline in CD4+, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: Cells per cubic millimeter
arithmetic mean (standard deviation)
Week -16, n=304	131.7 ( 172.69 )
Week -12, n=300	164.5 ( 174.61 )
Week -4, n=292	201.5 ( 195.53 )
Day 1, n=291	188.7 ( 186.69 )

No statistical analyses for this end point

Secondary: Number of Participants With AEs by their Severity Grades, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Number of Participants With AEs by their Severity Grades, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening. The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.

End point type

Secondary

End point timeframe

Up to 20 Weeks

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	56
Units: Participants
Maximum toxicity Grade 1	27
Maximum toxicity Grade 2	15
Maximum toxicity Grade 3	2
Maximum toxicity Grade 4	1

No statistical analyses for this end point

Secondary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Number of participants with maximum post-Baseline emergent toxicities for hematology parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Hematology parameters hemoglobin, platelet count, total neutrophils and white blood cell count were evaluated. Laboratory toxicities were graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Number of participants with any time post-baseline maximum emergent toxicities in any of the hematology parameters have been presented.

End point type

Secondary

End point timeframe

Up to Week 20

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Participants
Maximum toxicity Grade 1	26
Maximum toxicity Grade 2	4
Maximum toxicity Grade 3	1
Maximum toxicity Grade 4	3

No statistical analyses for this end point

Secondary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Top of page

End point title

Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

End point description

Clinical chemistry parameters AST, ALT, ALP, CO2/HCO3, cholesterol, CK, glucose, LDL cholesterol, lipase, potassium, and sodium, total TBIL and triglycerides were evaluated. Laboratory toxicities were graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Number of participants with any time post-baseline maximum emergent toxicities in any of the chemistry parameters have been presented.

End point type

Secondary

End point timeframe

Up to 20 weeks

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	309
Units: Participants
Maximum toxicity Grade 1	130
Maximum toxicity Grade 2	50
Maximum toxicity Grade 3	16
Maximum toxicity Grade 4	5

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK (Induction Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK (Induction Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	306
Units: International Units per Liter (IU/L)
arithmetic mean (standard deviation)
ALT, Week -16, n=306	0.4 ( 33.1 )
ALT, Week -12, n=301	-1.3 ( 14.1 )
ALT, Week -8, n=297	-0.5 ( 16.6 )
ALT, Week -4, n=292	1.5 ( 50.3 )
ALT, Day 1, n=287	-1.2 ( 18.0 )
ALP, Week -16, n=306	-2.1 ( 12.0 )
ALP, Week -12, n=301	-2.6 ( 11.0 )
ALP, Week -8, n=297	-1.2 ( 13.0 )
ALP, Week -4, n=292	0.1 ( 15.4 )
ALP, Day 1, n=287	0.1 ( 14.1 )
AST, Week -16, n=306	0.3 ( 33.4 )
AST, Week -12, n=301	-2.2 ( 13.1 )
AST, Week -8, n=296	-1.7 ( 15.8 )
AST, Week -4, n=292	-0.0 ( 30.9 )
AST, Day 1, n=286	-1.0 ( 25.9 )
CK, Week -16, n=306	19.0 ( 345.6 )
CK, Week -12, n=301	29.4 ( 485.4 )
CK, Week -8, n=297	26.3 ( 529.6 )
CK, Week -4, n=292	33.2 ( 434.2 )
CK, Day 1, n=287	69.9 ( 1164.7 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter: Albumin (Induction Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameter: Albumin (Induction Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameter: Albumin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	306
Units: Grams per Liter (G/L)
arithmetic mean (standard deviation)
Week -16, n=306	0.2 ( 2.3 )
Week -12, n=301	0.7 ( 2.3 )
Week -8, n=297	1.4 ( 2.6 )
Week -4, n=292	1.7 ( 2.6 )
Day 1, n=287	1.9 ( 2.8 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine (Induction Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine (Induction Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including total Bilirubin and Creatinine at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	306
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard deviation)
Total Bilirubin, Week -16, n=305	-0.6 ( 4.5 )
Total Bilirubin, Week -12, n=301	-0.9 ( 4.0 )
Total Bilirubin, Week -8, n=297	-1.0 ( 4.1 )
Total Bilirubin, Week -4, n=292	-0.5 ( 4.1 )
Total Bilirubin, Day 1, n=287	-0.3 ( 4.0 )
Creatinine, Week -16, n=306	2.6 ( 7.6 )
Creatinine, Week -12, n=301	1.5 ( 7.8 )
Creatinine, Week -8, n=297	1.6 ( 7.8 )
Creatinine, Week -4, n=292	3.5 ( 8.7 )
Creatinine, Day 1, n=287	4.6 ( 9.1 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea (Induction Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea (Induction Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including total CO2, chloride, cholesterol, glucose, potassium, sodium, triglyceride and urea at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	306
Units: Millimoles per Liter (mmol/L)
arithmetic mean (standard deviation)
CO2, Week -16, n=306	0.2 ( 2.4 )
CO2, Week -12, n=301	0.3 ( 2.3 )
CO2, Week -8, n=296	0.4 ( 2.3 )
CO2, Week -4, n=292	0.1 ( 2.3 )
CO2, Day 1, n=286	-0.8 ( 2.6 )
Chloride, Week -16, n=306	0.2 ( 2.3 )
Chloride, Week -12, n=301	0.5 ( 2.2 )
Chloride, Week -8, n=297	0.6 ( 2.3 )
Chloride, Week -4, n=292	0.2 ( 2.3 )
Chloride, Day 1, n=287	0.2 ( 2.3 )
Cholesterol, Week -16, n=255	0.21 ( 0.6 )
Cholesterol, Week -12, n=236	0.19 ( 0.5 )
Cholesterol, Week -8, n=235	0.27 ( 0.5 )
Cholesterol, Week -4, n=282	0.34 ( 0.5 )
Cholesterol, Day 1, n=285	0.34 ( 0.6 )
Glucose, Week -16, n=255	0.07 ( 0.7 )
Glucose, Week -12, n=236	0.16 ( 0.7 )
Glucose, Week -8, n=235	0.08 ( 0.7 )
Glucose, Week -4, n=281	0.06 ( 0.7 )
Glucose, Day 1, n=282	-0.01 ( 0.7 )
Potassium, Week -16, n=306	-0.05 ( 0.2 )
Potassium, Week -12, n=301	-0.03 ( 0.3 )
Potassium, Week -8, n=296	0.03 ( 0.3 )
Potassium, Week -4, n=292	0.03 ( 0.3 )
Potassium, Day 1, n=286	0.03 ( 0.3 )
Sodium, Week -16, n=306	-0.1 ( 1.8 )
Sodium, Week -12, n=301	0.1 ( 1.8 )
Sodium, Week -8, n=297	0.2 ( 1.9 )
Sodium, Week -4, n=292	0.4 ( 2.0 )
Sodium, Day 1, n=287	0.3 ( 1.9 )
Triglyceride, Week -16, n=3	-0.69 ( 0.1 )
Triglyceride, Week -12, n=2	-0.37 ( 0.1 )
Triglyceride, Week -8, n=2	0.29 ( 0.4 )
Triglyceride, Week -4, n=278	0.20 ( 0.9 )
Triglyceride, Day 1, n=278	-0.00 ( 0.7 )
Urea, Week -16, n=306	-0.06 ( 1.2 )
Urea, Week -12, n=301	-0.08 ( 1.2 )
Urea, Week -8, n=297	-0.09 ( 1.1 )
Urea, Week -4, n=292	-0.12 ( 1.3 )
Urea, Day 1, n=287	0.00 ( 1.2 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter: Lipase (Induction Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameter: Lipase (Induction Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameter: Lipase at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	306
Units: Units per Liter (U/L)
arithmetic mean (standard deviation)
Week -16, n=306	3.3 ( 20.0 )
Week -12, n=301	0.8 ( 15.3 )
Week -8, n=297	2.8 ( 24.3 )
Week -4, n=292	2.1 ( 23.8 )
Day 1, n=288	-1.2 ( 17.7 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and White Blood Cells (WBC) count (Induction Period)

Top of page

End point title

Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and White Blood Cells (WBC) count (Induction Period)

End point description

Blood samples were collected for the analysis of hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and WBC at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	303
Units: Giga cells per Liter
arithmetic mean (standard deviation)
Basophils, Week -16, n=303	0.00 ( 0.016 )
Basophils, Week -12, n=298	0.00 ( 0.019 )
Basophils, Week -8, n=297	0.00 ( 0.015 )
Basophils, Week -4, n=290	0.00 ( 0.016 )
Basophils, Day 1, n=290	0.00 ( 0.019 )
Eosinophils, Week -16, n=303	0.01 ( 0.131 )
Eosinophils, Week -12, n=298	0.01 ( 0.123 )
Eosinophils, Week -8, n=297	0.02 ( 0.127 )
Eosinophils, Week -4, n=290	0.02 ( 0.136 )
Eosinophils, Day 1, n=290	0.03 ( 0.161 )
Lymphocytes, Week -16, n=303	0.24 ( 0.541 )
Lymphocytes, Week -12, n=298	0.28 ( 0.573 )
Lymphocytes, Week -8, n=297	0.30 ( 0.541 )
Lymphocytes, Week -4, n=290	0.30 ( 0.574 )
Lymphocytes, Day 1, n=290	0.14 ( 0.565 )
Monocytes, Week -16, n=303	-0.00 ( 0.129 )
Monocytes, Week -12, n=298	0.00 ( 0.139 )
Monocytes, Week -8, n=297	-0.00 ( 0.135 )
Monocytes, Week -4, n=290	-0.00 ( 0.132 )
Monocytes, Day 1, n=290	0.00 ( 0.143 )
Platelet count, Week -16, n=302	14.4 ( 31.56 )
Platelet count, Week -12, n=300	18.2 ( 32.53 )
Platelet count, Week -8, n=297	21.1 ( 37.00 )
Platelet count, Week -4, n=290	23.0 ( 35.02 )
Platelet count, Day 1, n=290	22.2 ( 35.32 )
Total Neutrophils, Week -16, n=303	0.04 ( 1.185 )
Total Neutrophils, Week -12, n=298	0.22 ( 1.391 )
Total Neutrophils, Week -8, n=297	0.20 ( 1.286 )
Total Neutrophils, Week -4, n=290	0.31 ( 1.429 )
Total Neutrophils, Day 1, n=290	0.38 ( 1.515 )
WBC, Week -16, n=303	0.31 ( 1.318 )
WBC, Week -12, n=298	0.52 ( 1.522 )
WBC, Week -8, n=297	0.54 ( 1.460 )
WBC, Week -4, n=290	0.64 ( 1.594 )
WBC, Day 1, n=290	0.57 ( 1.713 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Hematocrit (Induction Period)

Top of page

End point title

Change from Baseline in hematology parameter: Hematocrit (Induction Period)

End point description

Blood samples were collected for the analysis of hematology parameter: Hematocrit at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)
Week -16, n=304	0.00 ( 0.022 )
Week -12, n=302	0.00 ( 0.023 )
Week -8, n=298	0.00 ( 0.024 )
Week -4, n=290	0.00 ( 0.025 )
Day 1, n=290	0.00 ( 0.025 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Hemoglobin (Induction Period)

Top of page

End point title

Change from Baseline in hematology parameter: Hemoglobin (Induction Period)

End point description

Blood samples were collected for the analysis of hematology parameter: Hemoglobin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: Grams per Liter
arithmetic mean (standard deviation)
Week -16, n=304	0.8 ( 6.94 )
Week -12, n=302	2.0 ( 7.07 )
Week -8, n=298	2.5 ( 7.42 )
Week -4, n=290	3.3 ( 7.95 )
Day 1, n=290	3.1 ( 7.96 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Mean Corpuscle Volume (Induction Period)

Top of page

End point title

Change from Baseline in hematology parameter: Mean Corpuscle Volume (Induction Period)

End point description

Blood samples were collected for the analysis of hematology parameter: Mean Corpuscle Volume at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: Femtoliters
arithmetic mean (standard deviation)
Week -16, n=304	1.0 ( 1.52 )
Week -12, n=302	2.1 ( 1.90 )
Week -8, n=298	3.1 ( 2.49 )
Week -4, n=290	4.0 ( 2.47 )
Day 1, n=290	4.4 ( 2.57 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Red Blood Cell count (Induction Period)

Top of page

End point title

Change from Baseline in hematology parameter: Red Blood Cell count (Induction Period)

End point description

Blood samples were collected for the analysis of hematology parameter: Red Blood Cell count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

Baseline (Week -20) and Week -16, Week -12, Week -8, Week -4, Day 1

End point values	CAB 30 mg+ABC/3TC QD (Induction Period)
Number of subjects analysed	304
Units: 10^12 cells per Liter
arithmetic mean (standard deviation)
Week -16, n=304	-0.05 ( 0.242 )
Week -12, n=302	-0.07 ( 0.254 )
Week -8, n=298	-0.10 ( 0.266 )
Week -4, n=290	-0.10 ( 0.284 )
Day 1, n=290	-0.14 ( 0.289 )

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV-1 RNA level <50 c/mL and <200 c/mL over Week 96 (Maintenance Period)

Top of page

End point title

Percentage of participants with plasma HIV-1 RNA level <50 c/mL and <200 c/mL over Week 96 (Maintenance Period)

End point description

Percentage of participants with HIV-1 RNA <50 c/mL and <200 c/mL was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders.

End point type

Secondary

End point timeframe

From Day 1 up to Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Percentage of participants
HIV-1 RNA<50 c/mL, Day 1	95	99	98
HIV-1 RNA<50 c/mL, Week 4	97	98	93
HIV-1 RNA<50 c/mL, Week 8	98	97	95
HIV-1 RNA<50 c/mL, Week 12	96	7	98
HIV-1 RNA<50 c/mL, Week 16	97	96	89
HIV-1 RNA<50 c/mL, Week 20	97	97	91
HIV-1 RNA<50 c/mL, Week 24	96	94	91
HIV-1 RNA<50 c/mL, Week 28	90	92	86
HIV-1 RNA<50 c/mL, Week 32	95	94	91
HIV-1 RNA<50 c/mL, Week 36	95	90	88
HIV-1 RNA<50 c/mL, Week 40	92	91	86
HIV-1 RNA<50 c/mL, Week 44	93	90	88
HIV-1 RNA<50 c/mL, Week 48	92	91	89
HIV-1 RNA<50 c/mL, Week 56	94	90	84
HIV-1 RNA<50 c/mL, Week 64	95	90	86
HIV-1 RNA<50 c/mL, Week 72	95	90	88
HIV-1 RNA<50 c/mL, Week 80	95	87	84
HIV-1 RNA<50 c/mL, Week 88	95	86	84
HIV-1 RNA<50 c/mL, Week 96	94	87	84
HIV-1 RNA<200 c/mL, Day 1	100	100	98
HIV-1 RNA<200 c/mL, Week 4	99	100	96
HIV-1 RNA<200 c/mL, Week 8	99	99	95
HIV-1 RNA<200 c/mL, Week 12	97	98	98
HIV-1 RNA<200 c/mL, Week 16	98	98	93
HIV-1 RNA<200 c/mL, Week 20	98	97	93
HIV-1 RNA<200 c/mL, Week 24	97	96	93
HIV-1 RNA<200 c/mL, Week 28	94	95	91
HIV-1 RNA<200 c/mL, Week 32	97	95	91
HIV-1 RNA<200 c/mL, Week 36	97	93	89
HIV-1 RNA<200 c/mL, Week 40	97	92	86
HIV-1 RNA<200 c/mL, Week 44	95	91	89
HIV-1 RNA<200 c/mL, Week 48	97	92	89
HIV-1 RNA<200 c/mL, Week 56	96	90	86
HIV-1 RNA<200 c/mL, Week 64	96	90	88
HIV-1 RNA<200 c/mL, Week 72	96	90	88
HIV-1 RNA<200 c/mL, Week 80	96	88	84
HIV-1 RNA<200 c/mL, Week 88	96	86	84
HIV-1 RNA<200 c/mL, Week 96	96	87	84

No statistical analyses for this end point

Secondary: Number of participants with protocol defined virologic failure at Week 32 and Week 48 (Maintenance Period)

Top of page

End point title

Number of participants with protocol defined virologic failure at Week 32 and Week 48 (Maintenance Period)

End point description

Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL.

End point type

Secondary

End point timeframe

At Week 32 and Week 48

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Week 32	1	0	1
Week 48	2	0	1

No statistical analyses for this end point

Secondary: Absolute value of plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Absolute value of plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

End point description

Plasma samples for quantitative HIV-1 RNA analysis were collected at indicated time points during Maintenance Period. Log10 values for HIV-1 RNA have been presented. SD=0.000 is defined as following: if participants analyzed at a specific timepoint have resulted same values, then SD is considered equal with 0.000.

End point type

Secondary

End point timeframe

At Week 32 and Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	108	50
Units: Log10 copies per milliliter
arithmetic mean (standard deviation)
Week 32	1.60 ( 0.044 )	1.59 ( 0.025 )	1.61 ( 0.112 )
Week 96	1.60 ( 0.056 )	1.59 ( 0.000 )	1.59 ( 0.000 )

No statistical analyses for this end point

Secondary: Change from Baseline in plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

End point description

Plasma samples for quantitative HIV-1 RNA analysis were collected at indicated time points during Maintenance Period. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as: HIV-1 RNA(log 10) at post-baseline visit minus HIV-1 RNA(log 10) at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	108	50
Units: Log10 copies per milliliter
arithmetic mean (standard deviation)
Week 32	-2.78 ( 0.610 )	-2.88 ( 0.709 )	-2.73 ( 0.561 )
Week 96	-2.77 ( 0.602 )	-2.89 ( 0.713 )	-2.77 ( 0.582 )

No statistical analyses for this end point

Secondary: Absolute value of CD4+ at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Absolute value of CD4+ at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry.

End point type

Secondary

End point timeframe

At Week 32 and Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	112	108	50
Units: Cells per cubic millimeter
arithmetic mean (standard deviation)
Week 32	752.3 ( 318.02 )	761.3 ( 293.07 )	891.3 ( 273.32 )
Week 96	748.6 ( 253.41 )	750.0 ( 271.11 )	906.8 ( 288.77 )

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+ at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in CD4+ at Week 32 and Week 96 (Maintenance Period)

End point description

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	112	108	50
Units: Cells per cubic millimeter
arithmetic mean (standard deviation)
Week 32	264.4 ( 247.84 )	263.7 ( 217.74 )	346.1 ( 219.59 )
Week 96	257.5 ( 192.25 )	270.6 ( 210.99 )	369.9 ( 226.60 )

No statistical analyses for this end point

Secondary: Number of Participants With HIV-1 Disease Progression over Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Number of Participants With HIV-1 Disease Progression over Week 32 and Week 96 (Maintenance Period)

End point description

HIV-associated conditions were recorded during the study and was assessed according to the Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. The clinical categories of HIV infection as per CDC system are class A=Asymptomatic HIV infection or lymphadenopathy or acute HIV infection; class B=symptomatic non-acquired immunodeficiency syndrome (AIDS) conditions and class C=AIDS indicator conditions. Number of participants experiencing disease progression is presented, where disease progression is defined as the progression from Baseline HIV disease status as follows: CDC class A at Baseline to CDC class C event; CDC Class B at Baseline to CDC Class C event; CDC Class C at Baseline to new CDC Class C event; and CDC class A, B or C at Baseline to death.

End point type

Secondary

End point timeframe

At Week 32 and Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
From CDC Stage 1 to CDC Stage 3 Event, Week 32	1	0	0
From CDC Stage 2 to CDC Stage 3 Event, Week 32	0	0	0
From CDC Stage 3 to New CDC Stage 3 Event, Week 32	0	0	0
From CDC Stage 1, 2 or 3 to Death, Week 32	0	1	0
From CDC Stage 1 to CDC Stage 3 Event, Week 96	4	0	0
From CDC Stage 2 to CDC Stage 3 Event, Week 96	0	0	0
From CDC Stage 3 to New CDC Stage 3 Event, Week 96	0	0	0
From CDC Stage 1, 2 or 3 to Death, Week 96	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With AEs by their Severity Grades over Week 96 (Maintenance Period)

Top of page

End point title

Number of Participants With AEs by their Severity Grades over Week 96 (Maintenance Period)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.

End point type

Secondary

End point timeframe

Up to Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Grade 1	23	21	24
Grade 2	71	74	26
Grade 3	19	18	4
Grade 4	2	2	0

No statistical analyses for this end point

Secondary: Number of Participants With AEs by their Severity Grades over Week 32 (Maintenance Period)

Top of page

End point title

Number of Participants With AEs by their Severity Grades over Week 32 (Maintenance Period)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity grading, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Participants
Grade 1	35	29	23
Grade 2	65	69	22
Grade 3	14	13	11
Grade 4	1	2	0

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK at Week 32 and Week 96 (Maintenance Period)

End point description

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: International Units per Liter
arithmetic mean (standard deviation)
ALT, Week 32	-2.4 ( 13.4 )	-2.7 ( 13.5 )	-5.0 ( 19.5 )
ALP, Week 32	-1.2 ( 14.6 )	-3.8 ( 15.0 )	-1.3 ( 11.6 )
AST, Week 32	-2.8 ( 12.5 )	-2.2 ( 14.5 )	-8.3 ( 30.6 )
CK, Week 32	51.4 ( 651.0 )	93.4 ( 446.9 )	38.8 ( 394.9 )
ALT, Week 96	1.8 ( 19.19 )	-2.2 ( 14.42 )	-2.7 ( 22.17 )
ALP, Week 96	-3.1 ( 15.59 )	-3.4 ( 15.64 )	-2.8 ( 12.34 )
AST, Week 96	-1.0 ( 15.45 )	-4.0 ( 9.31 )	-8.8 ( 32.57 )
CK, Week 96	21.1 ( 490.00 )	13.7 ( 153.92 )	-13.9 ( 227.98 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter: Albumin at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameter: Albumin at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including Albumin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	112	108	50
Units: Grams per Liter
arithmetic mean (standard deviation)
Week 32	1.4 ( 3.0 )	0.9 ( 2.9 )	1.1 ( 2.8 )
Week 96	1.0 ( 2.76 )	0.9 ( 2.87 )	0.2 ( 0.2 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including Total Bilirubin and Creatinine at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	112	108	50
Units: Micromoles per Liter
arithmetic mean (standard deviation)
Total Bilirubin, Week 32	0.8 ( 4.4 )	0.4 ( 3.6 )	-0.6 ( 4.4 )
Creatinine, Week 32	2.7 ( 8.5 )	3.8 ( 8.7 )	2.7 ( 6.1 )
Total Bilirubin, Week 96	0.0 ( 3.78 )	-0.3 ( 4.11 )	-1.1 ( 4.25 )
Creatinine, Week 96	3.11 ( 8.515 )	4.27 ( 8.730 )	4.42 ( 6.105 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters: Total CO2, chloride, cholesterol, glucose, potassium, sodium, triglyceride and urea at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameters: Total CO2, chloride, cholesterol, glucose, potassium, sodium, triglyceride and urea at Week 32 and Week 96 (Maintenance Period)

End point description

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	112	108	50
Units: Millimoles per Liter
arithmetic mean (standard deviation)
Total CO2, Week 32	-0.8 ( 2.1 )	-1.5 ( 2.4 )	-1.1 ( 2.4 )
Chloride, Week 32	-0.2 ( 0.3 )	2.4 ( 0.1 )	2.1 ( 0.2 )
Cholesterol, Week 32	0.37 ( 0.6 )	0.47 ( 0.7 )	0.25 ( 0.5 )
Glucose, Week 32	0.13 ( 1.0 )	0.03 ( 0.7 )	-0.05 ( 0.6 )
Potassium, Week 32	0.01 ( 0.3 )	-0.05 ( 0.3 )	-0.04 ( 0.2 )
Sodium, Week 32	0.4 ( 2.0 )	-0.1 ( 1.8 )	0.0 ( 1.7 )
Triglycerides, Week 32	0.08 ( 0.9 )	-0.00 ( 1.7 )	0.06 ( 0.7 )
Urea, Week 32	0.15 ( 1.3 )	0.23 ( 1.4 )	-0.01 ( 1.4 )
Total CO2, Week 96	-0.8 ( 2.88 )	-1.1 ( 2.64 )	-0.1 ( 2.47 )
Chloride, Week 96	-0.1 ( 2.32 )	-0.4 ( 2.53 )	0.3 ( 2.12 )
Cholesterol, Week 96	0.554 ( 0.6724 )	0.731 ( 0.7380 )	0.348 ( 0.6490 )
Glucose, Week 96	0.12 ( 0.729 )	0.11 ( 0.667 )	0.02 ( 0.745 )
Potassium, Week 96	0.11 ( 0.378 )	-0.04 ( 0.408 )	-0.03 ( 0.314 )
Sodium, Week 96	-0.1 ( 1.85 )	-0.4 ( 2.07 )	-0.4 ( 1.96 )
Triglycerides, Week 96	0.084 ( 0.9000 )	0.080 ( 1.4964 )	0.197 ( 0.4972 )
Urea, Week 96	0.09 ( 1.393 )	-0.01 ( 1.230 )	0.12 ( 1.461 )

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter: Lipase at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in clinical chemistry parameter: Lipase at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including Lipase at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	115	115	56
Units: Units per Liter
arithmetic mean (standard deviation)
Week 32	-1.2 ( 33.2 )	-4.4 ( 15.4 )	-3.9 ( 14.7 )
Week 96	3.5 ( 22.00 )	-0.8 ( 14.73 )	-2.3 ( 14.21 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelet count and WBC count at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelet count and WBC count at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of hematology parameters including Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelet count and WBC count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	110	107	48
Units: 10^9 cells per Liter
arithmetic mean (standard deviation)
Basophils, Week 32	0.00 ( 0.012 )	0.00 ( 0.022 )	0.00 ( 0.010 )
Eosinophils, Week 32	0.01 ( 0.146 )	0.23 ( 1.985 )	-0.01 ( 0.143 )
Lymphocytes, Week 32	0.34 ( 0.661 )	0.26 ( 0.694 )	0.48 ( 0.635 )
Monocytes, Week 32	-0.02 ( 0.152 )	-0.03 ( 0.144 )	0.00 ( 0.144 )
Platelet count, Week 32	18.7 ( 38.28 )	20.6 ( 44.93 )	11.6 ( 33.33 )
Total Neutrophils, Week 32	0.59 ( 1.505 )	0.34 ( 1.489 )	0.94 ( 1.365 )
WBC count, Week 32	0.93 ( 1.670 )	0.81 ( 2.881 )	1.41 ( 1.529 )
Basophils, Week 96	0.004 ( 0.0139 )	0.000 ( 0.0204 )	0.006 ( 0.0157 )
Eosinophils, Week 96	0.015 ( 0.1461 )	0.021 ( 0.1013 )	-0.013 ( 0.1528 )
Lymphocytes, Week 96	0.325 ( 0.6356 )	0.290 ( 0.6793 )	0.534 ( 0.5408 )
Monocytes, Week 96	-0.009 ( 0.1685 )	-0.014 ( 0.1781 )	-0.005 ( 0.1443 )
Platelet count, Week 96	21.9 ( 40.07 )	21.1 ( 41.49 )	15.3 ( 39.28 )
Total Neutrophils, Week 96	0.381 ( 1.3060 )	0.515 ( 1.6200 )	0.783 ( 1.0747 )
WBC count, Week 96	0.72 ( 1.545 )	0.82 ( 1.786 )	1.31 ( 1.144 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Hematocrit at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in hematology parameter: Hematocrit at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of hematology parameters including Hematocrit at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	107	48
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)
Week 32	0.01 ( 0.026 )	0.01 ( 0.027 )	0.01 ( 0.027 )
Week 96	0.0114 ( 0.02880 )	0.0134 ( 0.03125 )	0.0124 ( 0.02748 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Hemoglobin at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in hematology parameter: Hemoglobin at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of hematology parameters including Hemoglobin at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	107	48
Units: Grams per Liter
arithmetic mean (standard deviation)
Week 32	2.0 ( 8.56 )	0.8 ( 8.45 )	1.7 ( 8.38 )
Week 96	3.9 ( 8.95 )	4.3 ( 9.92 )	4.1 ( 8.11 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Mean Corpuscle Volume at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in hematology parameter: Mean Corpuscle Volume at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of hematology parameters including Mean Corpuscle Volume at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	107	48
Units: Femtoliters
arithmetic mean (standard deviation)
Week 32	2.5 ( 1.97 )	2.3 ( 2.54 )	7.1 ( 2.88 )
Week 96	0.1 ( 2.99 )	0.3 ( 2.54 )	5.3 ( 3.14 )

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter: Red Blood Cell count at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

Change from Baseline in hematology parameter: Red Blood Cell count at Week 32 and Week 96 (Maintenance Period)

End point description

Blood samples were collected for the analysis of hematology parameters including Red Blood Cell count at indicated time points. Baseline (Week -20) refers to the last available value up to and including the date of first induction period dosing with CAB 30 mg plus ABC/3TC. Change from Baseline was defined as value at post-baseline visit minus value at Baseline.

End point type

Secondary

End point timeframe

At Week 32 and Week 96 (compared with Baseline [Week -20])

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	111	107	48
Units: 10^12 cells per Liter
arithmetic mean (standard deviation)
Week 32	0.03 ( 0.286 )	0.02 ( 0.278 )	-0.20 ( 0.296 )
Week 96	0.12 ( 0.294 )	0.14 ( 0.310 )	-0.13 ( 0.293 )

No statistical analyses for this end point

Secondary: Average initial concentration (C0) and Maximum Plasma Concentration (Cmax) of CAB LA (Q4W IM and Q8W IM dosing) (Maintenance Period)

Top of page

End point title

Average initial concentration (C0) and Maximum Plasma Concentration (Cmax) of CAB LA (Q4W IM and Q8W IM dosing) (Maintenance Period)

End point description

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB LA. The PK Concentration Population included all participants who received CAB LA and/or RPV LA and underwent PK sampling during the study, and provided available CAB LA and/or RPV LA plasma concentration data.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Number of subjects analysed	115	115
Units: Micrograms per milliliter
geometric mean (geometric coefficient of variation)
C0	1.43 ( 54 )	2.35 ( 32 )
Cmax	3.55 ( 56 )	3.50 ( 39 )

No statistical analyses for this end point

Secondary: Trough concentration (Ctrough) of CAB LA (Q8W IM dosing) used for assessment of steady state (Maintenance Period)

Top of page

End point title

Trough concentration (Ctrough) of CAB LA (Q8W IM dosing) used for assessment of steady state (Maintenance Period)

End point description

Blood samples were collected at indicated time points for PK analysis of CAB LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for CAB LA (Q8W IM dosing) which were considered for the assessment of steady state are presented.

End point type

Secondary

End point timeframe

Pre-dose on Weeks 16, 24 and 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)
Number of subjects analysed	87
Units: Micrograms per milliliter
arithmetic mean (standard deviation)
Week 16, n=87	1.6902 ( 0.80471 )
Week 24, n=86	1.6051 ( 0.78254 )
Week 32, n=84	1.5330 ( 0.70822 )

No statistical analyses for this end point

Secondary: Average initial concentration (C0) and Cmax of RPV LA (Q4W IM and Q8W IM dosing) (Maintenance Period)

Top of page

End point title

Average initial concentration (C0) and Cmax of RPV LA (Q4W IM and Q8W IM dosing) (Maintenance Period)

End point description

Blood samples were collected at indicated time points for PK analysis of RPV LA. C0 and Cmax of RPV LA (Q4W IM and Q8W IM dosing) was evaluated.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Number of subjects analysed	115	115
Units: Nanograms per milliliter
geometric mean (geometric coefficient of variation)
C0	49.3 ( 41 )	77.2 ( 35 )
Cmax	104 ( 47 )	111 ( 40 )

No statistical analyses for this end point

Secondary: Ctrough of CAB LA (Q4W IM dosing) used for assessment of steady state (Maintenance Period)

Top of page

End point title

Ctrough of CAB LA (Q4W IM dosing) used for assessment of steady state (Maintenance Period)

End point description

Blood samples were collected at indicated time points for PK analysis of CAB LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for CAB LA (Q4W IM dosing) which were considered for the assessment of steady state are presented.

End point type

Secondary

End point timeframe

Pre-dose on Weeks 16, 20, 24, 28 and 32

End point values	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Number of subjects analysed	85
Units: Micrograms per milliliter
arithmetic mean (standard deviation)
Week 16, n=78	2.2703 ( 0.92102 )
Week 20, n=77	2.3861 ( 0.76176 )
Week 24, n=78	2.6342 ( 1.29093 )
Week 28, n=82	2.4365 ( 0.86420 )
Week 32, n=85	2.4715 ( 0.89893 )

No statistical analyses for this end point

Secondary: Ctrough of RPV LA (Q8W IM dosing) used for assessment of steady state (Maintenance Period)

Top of page

End point title

Ctrough of RPV LA (Q8W IM dosing) used for assessment of steady state (Maintenance Period)

End point description

Blood samples were collected at indicated time points for PK analysis of RPV LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for RPV LA (Q8W IM dosing) which were considered for the assessment of steady state are presented.

End point type

Secondary

End point timeframe

Pre-dose on Weeks 16, 24 and 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)
Number of subjects analysed	87
Units: Nanograms per milliliter
arithmetic mean (standard deviation)
Week 16, n=87	41.94 ( 17.575 )
Week 24, n=85	47.97 ( 22.341 )
Week 32, n=83	57.24 ( 22.926 )

No statistical analyses for this end point

Secondary: Ctrough of RPV LA (Q4W IM dosing) used for assessment of steady state (Maintenance Period)

Top of page

End point title

Ctrough of RPV LA (Q4W IM dosing) used for assessment of steady state (Maintenance Period)

End point description

Blood samples were collected at indicated time points for PK analysis of RPV LA. Ctrough is the lowest concentration reached by a drug before the next dose is administered. Ctrough for RPV LA (Q4W IM dosing) which were considered for the assessment of steady state are presented.

End point type

Secondary

End point timeframe

Pre-dose on Weeks 16, 20, 24, 28 and 32

End point values	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Number of subjects analysed	85
Units: Nanograms per milliliter
arithmetic mean (standard deviation)
Week 16, n=78	66.92 ( 25.986 )
Week 20, n=77	74.55 ( 29.156 )
Week 24, n=78	76.84 ( 27.976 )
Week 28, n=83	80.84 ( 31.297 )
Week 32, n=85	90.34 ( 34.549 )

No statistical analyses for this end point

Secondary: Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: area under plasma concentration-time curve from time zero to the end of dosing interval (AUC [0-tau]) of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “HIV-1 RNA<50 c/mL” (success) and the independent variable is PK parameter (AUC [0-tau]). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter AUC (0-tau). Standard Error (SE)=0.000 is defined as following: if for all participants was resulted same value for the specific timepoint, then SE is equal with 0.000.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	86	84	0 ^[8]
Units: Change in log odds
arithmetic mean (standard error)
CAB LA	0.00 ( 0.001 )	0.00 ( 0.002 )	( )
RPV LA	0.00 ( 0.000 )	0.00 ( 0.000 )	( )

Notes
[8] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: Average C0 of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “HIV-1 RNA<50 c/mL” (success) and the independent variable is PK parameter (Average C0). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Average C0.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	101	108	50
Units: Change in log odds
arithmetic mean (standard error)
CAB LA, n=100,108, 50	0.64 ( 0.837 )	2.39 ( 1.903 )	0.39 ( 0.528 )
RPV LA, n=101,104,49	0.00 ( 0.025 )	0.01 ( 0.039 )	-0.01 ( 0.020 )

No statistical analyses for this end point

Secondary: Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Pharmacodynamic Response (HIV-1 RNA<50 c/mL) in relation with PK parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between pharmacodynamics response (HIV-1 RNA<50 c/mL) at Week 32 and plasma PK parameter: Cmax of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “HIV-1 RNA<50 c/mL” (success) and the independent variable is PK parameter (Cmax). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Cmax.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	98	97	0 ^[9]
Units: Change in log odds
arithmetic mean (standard error)
CAB LA, n=98, 97,0	-0.01 ( 0.174 )	1.64 ( 1.707 )	( )
RPV LA, n=97,96,0	0.00 ( 0.010 )	0.01 ( 0.027 )	( )

Notes
[9] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Virologic Failure (from MSDF algorithm) in relation with PK parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Virologic Failure (from MSDF algorithm) in relation with PK parameter (AUC[0-tau]) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: AUC (0-tau) of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “virologic failure” and the independent variable is PK parameter (AUC [0-tau]). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter AUC (0-tau). SE=0.000 is defined as following: if for all participants was resulted same value for the specific timepoint, then SE is equal with 0.000.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	86	84	0 ^[10]
Units: Change in log odds
arithmetic mean (standard error)
CAB LA	0.00 ( 0.001 )	0.00 ( 0.002 )	( )
RPV LA	0.00 ( 0.000 )	0.00 ( 0.000 )	( )

Notes
[10] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Virologic Failure (from MSDF algorithm) in relation with PK parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Virologic Failure (from MSDF algorithm) in relation with PK parameter (Average C0) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: Average C0 of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “virologic failure” and the independent variable is PK parameter (Average C0). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Average C0.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	101	108	50
Units: Change in log odds
arithmetic mean (standard error)
CAB LA, n=100,108, 50	-1.01 ( 1.014 )	-2.39 ( 1.903 )	-0.53 ( 0.796 )
RPV LA, n=101,104,49	0.00 ( 0.027 )	-0.01 ( 0.039 )	-0.01 ( 0.038 )

No statistical analyses for this end point

Secondary: Virologic Failure (from MSDF algorithm) in relation with PK parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period)

Top of page

End point title

Virologic Failure (from MSDF algorithm) in relation with PK parameter (Cmax) of CAB LA and RPV LA at Week 32 (Maintenance Period)

End point description

Logistic regression was used to examine the correlation between virologic failure at Week 32 and plasma PK parameter: Cmax of CAB LA and RPV LA per arm using MSDF (Missing, Switch or Discontinuation = Failure) algorithm. Estimates were obtained from logistic statistical model where the dependent variable is “virologic failure” and the independent variable is PK parameter (Cmax). Slopes and standard error are presented. Estimated effect represents the change in log odds for a one-unit increase in the PK parameter Cmax.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	98	97	0 ^[11]
Units: Change in log odds
arithmetic mean (standard error)
CAB LA, n=98, 97,0	-0.45 ( 0.509 )	-1.64 ( 1.707 )	( )
RPV LA, n=97,96,0	0.00 ( 0.012 )	-0.01 ( 0.027 )	( )

Notes
[11] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Genotypic Resistance

Top of page

End point title

Number of Participants With Treatment-emergent Genotypic Resistance

End point description

Plasma samples were collected to assess treatment emergent Genotypic Resistance for participants who had confirmed virologic failure. Number of participants who had any Integrase Inhibitor (INI) mutations or major mutations of other classes (Nucleoside reverse transcriptase inhibitor [NRTI], Non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI])are presented.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	1	0 ^[12]	1
Units: Participants
INI mutations	0		0
Major mutations of other classes	0		0

Notes
[12] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Phenotypic Resistance

Top of page

End point title

Number of Participants With Treatment-emergent Phenotypic Resistance

End point description

Plasma samples were collected for drug resistance testing. Number of participants, with treatment emergent phenotypic resistance to INI, NNRTI, NRTI and/or PI were summarized. Overall susceptibility of the drug was categorized as sensitive, partially sensitive and resistant.

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	1	0 ^[13]	1
Units: Participants
INI, Sensitive	1		1
INI, Partially sensitive	0		0
INI, Resistant	0		0
NNRTI, Sensitive	1		1
NNRTI, Partially sensitive	0		0
NNRTI, Resistant	0		0
NRTI, Sensitive	1		1
NRTI, Partially sensitive	0		0
NRTI, Resistant	0		0
PI, Sensitive	1		1
PI, Partially sensitive	0		0
PI, Resistant	0		0

Notes
[13] - No participants in this group were included in this analysis.

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV-1 RNA level <50 c/mL over Week 32 by subgroups (Maintenance Period)

Top of page

End point title

Percentage of participants with plasma HIV-1 RNA level <50 c/mL over Week 32 by subgroups (Maintenance Period)

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant ART prior to the visit of interest, as non-responders. Data is presented for following subgroups: Baseline plasma HIV-1 RNA levels, Baseline CD4+ cell count, Race and HIV Risk factor (Homosexual contact [HC] and not injectable drug user).

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	99	94	49
Units: Percentage of participants
Baseline HIV-1 RNA<100000 c/mL, n=99,87,49	96	92	94
Baseline HIV-1 RNA>=100000 c/mL, n=16,28,7	88	100	71
Baseline HIV-1 RNA<1000 c/mL, n=0,3,1	0	100	100
Baseline HIV-1 RNA 1000 to<10000c/mL, n=26,25,13	100	84	92
Baseline HIV-1 RNA 1000 to <50000c/mL, n=50,42,25	49	39	24
Baseline HIV-1 RNA 50000 to<100000c/mL,n=23,17,10	87	100	90
Baseline HIV-1 RNA>=100000 to<200000c/mL,n=9,13,2	89	100	50
Baseline plasma HIV-1 RNA >=200000 c/mL, n=7,15,5	86	100	80
Baseline CD4+ cell count <200 cells/mm^3, n=3,2,0	100	100	0
Baseline CD4+ count 200 to<350cells/mm^3,n=30,23,8	97	100	88
Baseline CD4+ count >=350 cells/mm^3, n=82,90,48	94	92	92
Race-White, n=93,94,39	95	94	95
Race-Non-White, n=22,21,17	95	95	82
HC and not injectable drug user, n=98,90,40	96	94	90
No HC and not injectable drug user, n=17,25,16	88	92	94

No statistical analyses for this end point

Secondary: Percentage of participants with protocol defined virologic failure (PDVF) at Week 32 by subgroups(Maintenance Period)

Top of page

End point title

Percentage of participants with protocol defined virologic failure (PDVF) at Week 32 by subgroups(Maintenance Period)

End point description

Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL. Data is presented for following subgroups: Baseline plasma HIV-1 RNA levels, Baseline CD4+ cell count, Race and HIV Risk factor (Homosexual contact [HC] and not injectable drug user).

End point type

Secondary

End point timeframe

Up to Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	99	94	49
Units: Percentage of participants
Baseline HIV-1 RNA<100000 c/mL, n=99,87,49	3	1	0
Baseline HIV-1 RNA>=100000 c/mL, n=16,28,7	13	0	29
Baseline HIV-1 RNA<1000 c/mL, n=0,3,1	0	0	0
Baseline HIV-1 RNA 1000 to<10000c/mL, n=26,25,13	0	4	0
Baseline HIV-1 RNA 1000 to <50000c/mL, n=50,42,25	2	0	0
Baseline HIV-1 RNA 50000 to<100000c/mL,n=23,17,10	0	0	0
Baseline HIV-1 RNA>=100000 to<200000c/mL,n=9,13,2	11	0	50
Baseline plasma HIV-1 RNA >=200000 c/mL, n=7,15,5	14	0	20
Baseline CD4+ cell count <200 cells/mm^3, n=3,2,0	0	0	0
Baseline CD4+ count 200 to<350cells/mm^3,n=30,23,8	0	0	13
Baseline CD4+ count >=350 cells/mm^3, n=82,90,48	6	1	2
Race-White, n=93,94,39	4	1	0
Race-Non-White, n=22,21,17	5	0	12
HC and not injectable drug user, n=98,90,40	3	1	5
No HC and not injectable drug user, n=17,25,16	12	0	0

No statistical analyses for this end point

Secondary: HIV treatment satisfaction questionnaire - status version (HIVTSQ[s]) Total Score at Week 32 and Week 96 (Maintenance Period)

Top of page

End point title

HIV treatment satisfaction questionnaire - status version (HIVTSQ[s]) Total Score at Week 32 and Week 96 (Maintenance Period)

End point description

The HIVTSQ(s) was developed to evaluate treatments for HIV and participant satisfaction. It has total 14 items and each items are scored from 6 (very satisfied) to 0 (very dissatisfied). Items 1 to 12 are summed to produce the Total Treatment Satisfaction Score with a possible range of 0 to 72. Higher scores represent greater treatment satisfaction as compared to the past few weeks.

End point type

Secondary

End point timeframe

At Week 32 and Week 96

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	109	106	50
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 32	68.4 ( 4.48 )	66.6 ( 6.47 )	65.1 ( 5.83 )
Week 96	68.4 ( 4.34 )	67.0 ( 5.20 )	63.5 ( 9.75 )

No statistical analyses for this end point

Secondary: HIV treatment satisfaction questionnaire - change version (HIVTSQ[c]) Total Score at Week 32 (Maintenance Period)

Top of page

End point title

HIV treatment satisfaction questionnaire - change version (HIVTSQ[c]) Total Score at Week 32 (Maintenance Period)

End point description

The HIVTSQ(c) was developed to evaluate treatments for HIV and participant satisfaction. It has total 14 items and each items are scored from +3 (‘much more satisfied’, ‘much more convenient’, ‘much more flexible’, etc.) to -3 (‘much less satisfied’, ‘much less convenient’, ‘much less flexible’, etc.). Items 1 to 12 (excluding Items 7b and 9b) are summed to produce a Total Treatment Satisfaction Score (change) with a possible range of -33 to +33. The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.

End point type

Secondary

End point timeframe

Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	106	100	49
Units: Scores on a scale
arithmetic mean (standard deviation)	30.9 ( 7.56 )	28.9 ( 8.53 )	20.5 ( 14.09 )

No statistical analyses for this end point

Secondary: Number of participants with HIV Medication Questionnaire (HIVMQ) Item E and F Scores at Week 32 (Maintenance Period)

Top of page

End point title

Number of participants with HIV Medication Questionnaire (HIVMQ) Item E and F Scores at Week 32 (Maintenance Period)

End point description

The HIVMQ was developed to assess participant reported medication adherence. It has 6 items (a, b, c, d, e, f). Item E (How often do you find it inconvenient or difficult to take/receive medication as recommended?) and Item F (How much pain/discomfort have experienced with this medication?). Each of these 2 items are scored from 0 (none of the time) to 6 (all of the time). The higher the score, the greater the adherence to medication. Number of participants with HIVMQ Item E and F Scores at Week 32 by their score categories (0: none of the time to 6: all of the time) are presented.

End point type

Secondary

End point timeframe

Week 32

End point values	CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	109	106	50
Units: Participants
Item E, score 0	80	73	16
Item E, score 1	12	14	13
Item E, score 2	3	2	2
Item E, score 3	2	6	3
Item E, score 4	0	1	1
Item E, score 5	2	4	12
Item E, score 6	10	6	3
Item F, Score 0	40	33	29
Item F, Score 1	35	43	12
Item F, Score 2	17	16	2
Item F, Score 3	6	5	2
Item F, Score 4	7	3	2
Item F, Score 5	4	4	0
Item F, Score 6	0	2	2

No statistical analyses for this end point

Secondary: Number of participants with HIV Medication Questionnaire (HIVMQ) Item E and F Scores at Week 96 (Maintenance Period)

Top of page

End point title

Number of participants with HIV Medication Questionnaire (HIVMQ) Item E and F Scores at Week 96 (Maintenance Period)

End point description

The HIVMQ was developed to assess participant reported medication adherence. It has 6 items (a, b, c, d, e, f). Item E (How often do you find it inconvenient or difficult to take/receive medication as recommended?) and Item F (How much pain/discomfort have experienced with this medication?). Each of these 2 items are scored from 0 (none of the time) to 6 (all of the time). The higher the score, the greater the adherence to medication. Number of participants with HIVMQ Item E and F Scores at Week 96 by their score categories (0: none of the time to 6: all of the time) are presented. Analysis was performed on the participants that received exclusively an oral regimen during the 96-weeks period [CAB 30mg+ABC/3TC QD (Induction Period and Maintenance Period) group], as pre-specified in Protocol.

End point type

Secondary

End point timeframe

Week 96

End point values	CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period)
Number of subjects analysed	46
Units: Participants
Item E, score 0	18
Item E, score 1	10
Item E, score 2	3
Item E, score 3	32
Item E, score 4	1
Item E, score 5	9
Item E, score 6	3
Item F, Score 0	3
Item F, Score 1	8
Item F, Score 2	4
Item F, Score 3	1
Item F, Score 4	0
Item F, Score 5	1
Item F, Score 6	1

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

All-cause mortality, SAEs and non-SAEs were collected from start of the study treatment up to end of Extension and LTFU Periods (up to approximately 468 weeks).

Adverse event reporting additional description

Safety population included all randomized participants who received at least one dose of study drug, based on the study phase they were included in.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Long-Term Follow-Up Group

Reporting group description

Reporting group title

CAB 30 mg+ABC/3TC QD (Induction Period)

Reporting group description

Reporting group title

CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)

Reporting group description

Reporting group title

Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)

Reporting group description

Reporting group title

CAB 30 mg+ABC/3TC QD (Induction and Maintenance)

Reporting group description

Reporting group title

Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension)

Reporting group description

Reporting group title

CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)

Reporting group description

Serious adverse events	Long-Term Follow-Up Group	CAB 30 mg+ABC/3TC QD (Induction Period)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)	CAB 30 mg+ABC/3TC QD (Induction and Maintenance)	Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 43 (16.28%)	8 / 309 (2.59%)	31 / 115 (26.96%)	1 / 10 (10.00%)	9 / 56 (16.07%)	9 / 34 (26.47%)	31 / 115 (26.96%)
number of deaths (all causes)	0	1	0	0	0	0	3
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningioma
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasm prostate
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal neoplasm
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic dilatation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Flushing
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Hernia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	2 / 115 (1.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Eosinophilic granulomatosis with polyangiitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Benign prostatic hyperplasia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic prolapse
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthmatic crisis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasal septum deviation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	2 / 43 (4.65%)	0 / 309 (0.00%)	2 / 115 (1.74%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Substance abuse
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug abuse
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adjustment disorder
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alcohol withdrawal syndrome
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar I disorder
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Delusion
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression suicidal
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dissociation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mania
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychotic behaviour
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric decompensation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aggression
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	2 / 115 (1.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epicondylitis
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine perforation
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	2 / 115 (1.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Accidental overdose
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alcohol poisoning
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Carbon monoxide poisoning
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon injury
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypobarism
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jaw fracture
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Buried penis syndrome
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Acute myocardial infarction
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Headache
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nerve root compression
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	2 / 115 (1.74%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cognitive disorder
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coma
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukoencephalopathy
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Motor neurone disease
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Polyneuropathy alcoholic
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VIth nerve paralysis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	1 / 10 (10.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Splenic vein thrombosis
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Blindness
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer perforation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal food impaction
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Portal vein thrombosis
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic hepatitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis alcoholic
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Toxic skin eruption
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	2 / 115 (1.74%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	2 / 115 (1.74%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Neck pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	2 / 115 (1.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 43 (0.00%)	1 / 309 (0.32%)	1 / 115 (0.87%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	2 / 115 (1.74%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaria
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Shigella infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	1 / 34 (2.94%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Obesity
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	1 / 115 (0.87%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	1 / 115 (0.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Long-Term Follow-Up Group	CAB 30 mg+ABC/3TC QD (Induction Period)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)	Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension)	CAB 30 mg+ABC/3TC QD (Induction and Maintenance)	Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension)	CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension)
Total subjects affected by non serious adverse events
subjects affected / exposed	7 / 43 (16.28%)	145 / 309 (46.93%)	115 / 115 (100.00%)	10 / 10 (100.00%)	52 / 56 (92.86%)	34 / 34 (100.00%)	115 / 115 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	2 / 10 (20.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	18 / 115 (15.65%)
occurrences all number	0	0	19	2	0	2	22
Skin papilloma
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	10	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	10 / 115 (8.70%)
occurrences all number	0	0	12	0	0	0	14
General disorders and administration site conditions
Injection site swelling
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	41 / 115 (35.65%)	3 / 10 (30.00%)	0 / 56 (0.00%)	6 / 34 (17.65%)	43 / 115 (37.39%)
occurrences all number	0	0	209	3	0	9	293
Injection site pain
subjects affected / exposed	4 / 43 (9.30%)	0 / 309 (0.00%)	111 / 115 (96.52%)	8 / 10 (80.00%)	0 / 56 (0.00%)	31 / 34 (91.18%)	114 / 115 (99.13%)
occurrences all number	4	0	2749	197	0	486	3533
Injection site bruising
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	24 / 115 (20.87%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	18 / 115 (15.65%)
occurrences all number	0	0	65	0	0	0	93
Injection site warmth
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	32 / 115 (27.83%)	2 / 10 (20.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	29 / 115 (25.22%)
occurrences all number	0	0	161	2	0	5	218
Fatigue
subjects affected / exposed	0 / 43 (0.00%)	19 / 309 (6.15%)	13 / 115 (11.30%)	1 / 10 (10.00%)	4 / 56 (7.14%)	3 / 34 (8.82%)	19 / 115 (16.52%)
occurrences all number	0	19	14	2	5	3	28
Pyrexia
subjects affected / exposed	3 / 43 (6.98%)	0 / 309 (0.00%)	23 / 115 (20.00%)	0 / 10 (0.00%)	3 / 56 (5.36%)	3 / 34 (8.82%)	20 / 115 (17.39%)
occurrences all number	3	0	33	0	3	4	33
Injection site induration
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	32 / 115 (27.83%)	1 / 10 (10.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	33 / 115 (28.70%)
occurrences all number	0	0	156	1	0	4	263
Injection site nodule
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	46 / 115 (40.00%)	5 / 10 (50.00%)	0 / 56 (0.00%)	12 / 34 (35.29%)	57 / 115 (49.57%)
occurrences all number	0	0	327	14	0	34	675
Injection site pruritus
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	40 / 115 (34.78%)	2 / 10 (20.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	40 / 115 (34.78%)
occurrences all number	0	0	285	3	0	10	305
Asthenia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	1 / 10 (10.00%)	9 / 56 (16.07%)	3 / 34 (8.82%)	14 / 115 (12.17%)
occurrences all number	0	0	14	1	11	4	19
Injection site erythema
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	20 / 115 (17.39%)	1 / 10 (10.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	23 / 115 (20.00%)
occurrences all number	0	0	66	1	0	5	122
Injection site haematoma
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	6 / 115 (5.22%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	13 / 115 (11.30%)
occurrences all number	0	0	11	0	0	6	69
Injection site discolouration
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	8 / 115 (6.96%)
occurrences all number	0	0	20	0	0	0	11
Influenza like illness
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	15 / 115 (13.04%)
occurrences all number	0	0	11	0	0	0	27
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	6 / 115 (5.22%)
occurrences all number	0	0	12	0	0	0	6
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	1 / 10 (10.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	0 / 115 (0.00%)
occurrences all number	0	0	0	1	0	2	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	14 / 115 (12.17%)	0 / 10 (0.00%)	3 / 56 (5.36%)	4 / 34 (11.76%)	13 / 115 (11.30%)
occurrences all number	0	0	17	0	4	4	18
Cough
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	19 / 115 (16.52%)	2 / 10 (20.00%)	7 / 56 (12.50%)	4 / 34 (11.76%)	26 / 115 (22.61%)
occurrences all number	0	0	26	5	8	4	39
Rhinitis allergic
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	14 / 115 (12.17%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	10 / 115 (8.70%)
occurrences all number	0	0	20	0	0	0	12
Catarrh
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	3 / 56 (5.36%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	4	0	0
Rhinorrhoea
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	3 / 56 (5.36%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	3	0	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	15 / 115 (13.04%)	0 / 10 (0.00%)	5 / 56 (8.93%)	4 / 34 (11.76%)	11 / 115 (9.57%)
occurrences all number	0	0	19	0	6	5	15
Anxiety
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	22 / 115 (19.13%)	1 / 10 (10.00%)	4 / 56 (7.14%)	3 / 34 (8.82%)	20 / 115 (17.39%)
occurrences all number	0	0	31	1	4	3	24
Insomnia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	19 / 115 (16.52%)	0 / 10 (0.00%)	4 / 56 (7.14%)	4 / 34 (11.76%)	14 / 115 (12.17%)
occurrences all number	0	0	20	0	4	5	15
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	12 / 115 (10.43%)
occurrences all number	0	0	0	0	0	3	15
Contusion
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	2 / 10 (20.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	13 / 115 (11.30%)
occurrences all number	0	0	10	2	0	2	17
Limb injury
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	6 / 115 (5.22%)	1 / 10 (10.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	6 / 115 (5.22%)
occurrences all number	0	0	7	1	0	2	6
Exposure to communicable disease
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	1 / 10 (10.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	0 / 115 (0.00%)
occurrences all number	0	0	0	1	0	3	0
Skin laceration
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	7 / 115 (6.09%)
occurrences all number	0	0	9	0	0	0	7
Penis injury
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	0	3	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 43 (0.00%)	27 / 309 (8.74%)	30 / 115 (26.09%)	1 / 10 (10.00%)	14 / 56 (25.00%)	3 / 34 (8.82%)	30 / 115 (26.09%)
occurrences all number	0	27	51	1	19	6	56
Dizziness
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	1 / 10 (10.00%)	3 / 56 (5.36%)	2 / 34 (5.88%)	11 / 115 (9.57%)
occurrences all number	0	0	13	1	3	2	16
Sciatica
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	7 / 115 (6.09%)
occurrences all number	0	0	12	0	0	3	10
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 43 (0.00%)	34 / 309 (11.00%)	39 / 115 (33.91%)	3 / 10 (30.00%)	11 / 56 (19.64%)	4 / 34 (11.76%)	35 / 115 (30.43%)
occurrences all number	0	34	55	3	13	5	59
Nausea
subjects affected / exposed	3 / 43 (6.98%)	38 / 309 (12.30%)	9 / 115 (7.83%)	0 / 10 (0.00%)	9 / 56 (16.07%)	0 / 34 (0.00%)	14 / 115 (12.17%)
occurrences all number	3	38	10	0	11	0	25
Abdominal pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	14 / 115 (12.17%)	1 / 10 (10.00%)	4 / 56 (7.14%)	3 / 34 (8.82%)	14 / 115 (12.17%)
occurrences all number	0	0	18	1	5	3	14
Vomiting
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	4 / 56 (7.14%)	0 / 34 (0.00%)	8 / 115 (6.96%)
occurrences all number	0	0	9	0	5	0	13
Dyspepsia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	13 / 115 (11.30%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	7 / 115 (6.09%)
occurrences all number	0	0	13	0	0	0	10
Constipation
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	11 / 115 (9.57%)
occurrences all number	0	0	13	0	0	0	15
Odynophagia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	4 / 56 (7.14%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	6	0	0
Anogenital dysplasia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	0	6	0
Abdominal pain upper
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	10 / 115 (8.70%)
occurrences all number	0	0	10	0	0	0	11
Toothache
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	13 / 115 (11.30%)	1 / 10 (10.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	14 / 115 (12.17%)
occurrences all number	0	0	17	1	0	3	19
Gastritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	3 / 56 (5.36%)	0 / 34 (0.00%)	8 / 115 (6.96%)
occurrences all number	0	0	0	0	3	0	10
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	11 / 115 (9.57%)
occurrences all number	0	0	9	0	0	0	12
Haemorrhoids
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	14 / 115 (12.17%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	12 / 115 (10.43%)
occurrences all number	0	0	17	0	0	0	13
Proctitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	7 / 115 (6.09%)
occurrences all number	0	0	14	0	0	0	10
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	6 / 56 (10.71%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	8	0	8	0	0
Rash
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	2 / 10 (20.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	11 / 115 (9.57%)
occurrences all number	0	0	11	3	0	0	13
Pruritus
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	7 / 115 (6.09%)
occurrences all number	0	0	11	0	0	0	8
Musculoskeletal and connective tissue disorders
Neck pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	0 / 10 (0.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	6 / 115 (5.22%)
occurrences all number	0	0	13	0	0	4	8
Pain in extremity
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	14 / 115 (12.17%)
occurrences all number	0	0	14	0	0	3	19
Arthralgia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	27 / 115 (23.48%)	3 / 10 (30.00%)	4 / 56 (7.14%)	6 / 34 (17.65%)	21 / 115 (18.26%)
occurrences all number	0	0	45	5	7	9	34
Myalgia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	1 / 56 (1.79%)	0 / 34 (0.00%)	13 / 115 (11.30%)
occurrences all number	0	0	14	0	1	0	18
Back pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	27 / 115 (23.48%)	3 / 10 (30.00%)	10 / 56 (17.86%)	8 / 34 (23.53%)	30 / 115 (26.09%)
occurrences all number	0	0	39	4	12	16	55
Muscle contracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	9 / 115 (7.83%)
occurrences all number	0	0	9	0	0	0	10
Infections and infestations
Nasopharyngitis
subjects affected / exposed	0 / 43 (0.00%)	27 / 309 (8.74%)	54 / 115 (46.96%)	5 / 10 (50.00%)	22 / 56 (39.29%)	8 / 34 (23.53%)	54 / 115 (46.96%)
occurrences all number	0	27	129	13	39	11	146
Upper respiratory tract infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	30 / 115 (26.09%)	1 / 10 (10.00%)	7 / 56 (12.50%)	9 / 34 (26.47%)	28 / 115 (24.35%)
occurrences all number	0	0	55	1	9	12	42
Syphilis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	36 / 115 (31.30%)	3 / 10 (30.00%)	6 / 56 (10.71%)	4 / 34 (11.76%)	28 / 115 (24.35%)
occurrences all number	0	0	61	3	7	5	46
Pharyngitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	19 / 115 (16.52%)	0 / 10 (0.00%)	5 / 56 (8.93%)	6 / 34 (17.65%)	21 / 115 (18.26%)
occurrences all number	0	0	25	0	5	8	32
Bronchitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	19 / 115 (16.52%)	0 / 10 (0.00%)	6 / 56 (10.71%)	6 / 34 (17.65%)	17 / 115 (14.78%)
occurrences all number	0	0	25	0	6	9	26
Gastroenteritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	28 / 115 (24.35%)	0 / 10 (0.00%)	5 / 56 (8.93%)	8 / 34 (23.53%)	23 / 115 (20.00%)
occurrences all number	0	0	43	0	5	10	36
Influenza
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	21 / 115 (18.26%)	3 / 10 (30.00%)	0 / 56 (0.00%)	7 / 34 (20.59%)	32 / 115 (27.83%)
occurrences all number	0	0	26	4	0	10	45
Respiratory tract infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	1 / 10 (10.00%)	6 / 56 (10.71%)	2 / 34 (5.88%)	11 / 115 (9.57%)
occurrences all number	0	0	14	1	8	3	17
Gonorrhoea
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	15 / 115 (13.04%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	8 / 115 (6.96%)
occurrences all number	0	0	25	0	0	0	10
Conjunctivitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	15 / 115 (13.04%)	1 / 10 (10.00%)	3 / 56 (5.36%)	3 / 34 (8.82%)	10 / 115 (8.70%)
occurrences all number	0	0	18	2	3	3	11
Urethritis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	11 / 115 (9.57%)
occurrences all number	0	0	12	0	0	0	16
Sinusitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	10 / 115 (8.70%)	1 / 10 (10.00%)	4 / 56 (7.14%)	3 / 34 (8.82%)	12 / 115 (10.43%)
occurrences all number	0	0	23	1	5	3	18
Oral herpes
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	17 / 115 (14.78%)
occurrences all number	0	0	28	0	0	0	23
Tonsillitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	1 / 10 (10.00%)	4 / 56 (7.14%)	3 / 34 (8.82%)	11 / 115 (9.57%)
occurrences all number	0	0	14	1	4	7	15
Rhinitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	3 / 56 (5.36%)	0 / 34 (0.00%)	16 / 115 (13.91%)
occurrences all number	0	0	9	0	3	0	19
Chlamydial infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	13 / 115 (11.30%)	1 / 10 (10.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	7 / 115 (6.09%)
occurrences all number	0	0	19	1	0	3	7
Folliculitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	6 / 115 (5.22%)
occurrences all number	0	0	11	0	0	0	7
Gastroenteritis viral
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	2 / 10 (20.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	0 / 115 (0.00%)
occurrences all number	0	0	0	2	0	2	0
Herpes zoster
subjects affected / exposed	1 / 43 (2.33%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	12 / 115 (10.43%)
occurrences all number	1	0	11	0	0	0	20
Tooth infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	11 / 115 (9.57%)
occurrences all number	0	0	0	0	0	0	16
Subcutaneous abscess
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	7 / 115 (6.09%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	9 / 115 (7.83%)
occurrences all number	0	0	7	0	0	0	10
Viral infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	6 / 115 (5.22%)	0 / 10 (0.00%)	3 / 56 (5.36%)	3 / 34 (8.82%)	9 / 115 (7.83%)
occurrences all number	0	0	6	0	3	3	10
Ear infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	6 / 115 (5.22%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	9 / 115 (7.83%)
occurrences all number	0	0	8	0	0	5	11
Proctitis chlamydial
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	1 / 10 (10.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	0 / 115 (0.00%)
occurrences all number	0	0	18	1	0	2	0
Tinea versicolour
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	0 / 115 (0.00%)
occurrences all number	0	0	0	0	0	4	0
Urinary tract infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	6 / 115 (5.22%)
occurrences all number	0	0	21	0	0	0	9
Anal chlamydia infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	11	0	0	0	0
Onychomycosis
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	6 / 115 (5.22%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	6 / 115 (5.22%)
occurrences all number	0	0	8	0	0	0	8
Oropharyngeal gonococcal infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	11 / 115 (9.57%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	26	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	1 / 10 (10.00%)	0 / 56 (0.00%)	2 / 34 (5.88%)	8 / 115 (6.96%)
occurrences all number	0	0	0	1	0	2	10
Proctitis gonococcal
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	12 / 115 (10.43%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	7 / 115 (6.09%)
occurrences all number	0	0	29	0	0	0	9
Urethritis gonococcal
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	8 / 115 (6.96%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	13	0	0	0	0
COVID-19
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	25 / 115 (21.74%)	2 / 10 (20.00%)	0 / 56 (0.00%)	9 / 34 (26.47%)	28 / 115 (24.35%)
occurrences all number	0	0	29	2	0	9	34
Suspected COVID-19
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	0 / 115 (0.00%)
occurrences all number	0	0	13	0	0	4	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	9 / 115 (7.83%)	0 / 10 (0.00%)	0 / 56 (0.00%)	3 / 34 (8.82%)	9 / 115 (7.83%)
occurrences all number	0	0	11	0	0	3	10
Vitamin D deficiency
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	14 / 115 (12.17%)	0 / 10 (0.00%)	0 / 56 (0.00%)	0 / 34 (0.00%)	0 / 115 (0.00%)
occurrences all number	0	0	15	0	0	0	0
Dyslipidaemia
subjects affected / exposed	0 / 43 (0.00%)	0 / 309 (0.00%)	0 / 115 (0.00%)	1 / 10 (10.00%)	0 / 56 (0.00%)	4 / 34 (11.76%)	0 / 115 (0.00%)
occurrences all number	0	0	0	1	0	4	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Oct 2013

Amendment 1: was finalized 28 October 2013, however, was never implemented due to a design change requiring a second amendment. Amendment 1 was prepared to address the following changes: universal changes to naming conventions for the long acting formulation of CAB, simplifying the protocol summary to allow better understanding of the protocol, clarifying the study schematic to increase understanding, clarification the purpose of and analyses to be performed by the Independent Data Monitoring Committee to reflect current plans, clarification of the intent of the Day 1 analysis as a possible analysis if needed, clarification to study treatments including the addition of the ingredients of the long acting formulations of both study treatments, clarification of health outcomes objectives, timings and questionnaires, adding the assessment of exercises habits and intravenous drug use, removing some assessments to simplify study visits, updates and simplification to the time and events tables and additional miscellaneous clarifications.

23 Jan 2014

Amendment No.02: Primary modifications included, Study design adapted to consolidate the Induction Period into a single 20 Week arm and for the addition of an every 8 week IM regimen into the Maintenance Period. Increased sample size to 265 subjects. Primary endpoint changed from Week 24 to Week 32. Dose rationale updated.

13 Jun 2014

Amendment No.03: Primary modifications included, ABC/3TC added as Investigational Product beginning at Day 1 of the Maintenance Period; clarification that alternative background therapy (if positive for HLA-B*5701) is not counted as the protocol permitted switch for NRTI; clarification regarding provision of alternative NRTI therapy; change in visit window for subjects on the oral dosing arm; excursion temperatures added for ABC/3TC and RPV oral tablet; text added for ABC/3TC overdose; deleted option for participant informed consent by legal representative; Time and Events Table clarifications. Additional clarifications and typographical corrections throughout.

22 Apr 2015

Amendment No. 4: Primary modifications included, addition of a 2-hour post dose pharmacokinetic samples and electrocardiogram at Week 32 and Week 48 for subjects receiving intramuscular CAB LA and RPV LA; addition of LAI116482 Week 96 data; addition of maladministration of injection risk; additional clarifications for injection site reaction collection; clarified visit windows.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) level below 50 copies/milliliter (c/mL) at Week 32

Primary: Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) level below 50 copies/milliliter (c/mL) at Week 32

Primary: Number of participants with protocol defined virologic failure (PDVF) until Week 32

Primary: Number of participants with protocol defined virologic failure (PDVF) until Week 32

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Induction Period)

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Induction Period)

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Maintenance Period)

Primary: Number of participants with any serious adverse event (SAE) and any non-serious adverse event (non-SAE) (Maintenance Period)

Primary: Number of participants with post-Baseline adverse events by maximum toxicity Grade

Primary: Number of participants with post-Baseline adverse events by maximum toxicity Grade

Primary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters

Primary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters

Primary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters

Primary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters

Primary: Number of participants with post-Baseline urinalysis dipstick results

Primary: Number of participants with post-Baseline urinalysis dipstick results

Secondary: Percentage of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Percentage of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Absolute values of plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Absolute values of plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Change from Baseline in plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Change from Baseline in plasma HIV-1 RNA, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Absolute values of cluster of differentiation 4+ (CD4+), for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Absolute values of cluster of differentiation 4+ (CD4+), for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Change from Baseline in CD4+, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Change from Baseline in CD4+, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of Participants With AEs by their Severity Grades, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of Participants With AEs by their Severity Grades, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of participants with maximum post-Baseline emergent toxicities for hematology parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Number of participants with maximum post-Baseline emergent toxicities for clinical chemistry parameters, for oral dose of CAB 30 mg plus ABC/3TC (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameter: Albumin (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameter: Albumin (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: Total Bilirubin and Creatinine (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameters: CO2, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameter: Lipase (Induction Period)

Secondary: Change from Baseline in clinical chemistry parameter: Lipase (Induction Period)

Secondary: Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and White Blood Cells (WBC) count (Induction Period)

Secondary: Change from Baseline in hematology parameters: Basophil, Eosinophils, Lymphocytes, Total Neutrophils, Monocytes, Platelets count and White Blood Cells (WBC) count (Induction Period)

Secondary: Change from Baseline in hematology parameter: Hematocrit (Induction Period)

Secondary: Change from Baseline in hematology parameter: Hematocrit (Induction Period)

Secondary: Change from Baseline in hematology parameter: Hemoglobin (Induction Period)

Secondary: Change from Baseline in hematology parameter: Hemoglobin (Induction Period)

Secondary: Change from Baseline in hematology parameter: Mean Corpuscle Volume (Induction Period)

Secondary: Change from Baseline in hematology parameter: Mean Corpuscle Volume (Induction Period)

Secondary: Change from Baseline in hematology parameter: Red Blood Cell count (Induction Period)

Secondary: Change from Baseline in hematology parameter: Red Blood Cell count (Induction Period)

Secondary: Percentage of participants with plasma HIV-1 RNA level <50 c/mL and <200 c/mL over Week 96 (Maintenance Period)

Secondary: Percentage of participants with plasma HIV-1 RNA level <50 c/mL and <200 c/mL over Week 96 (Maintenance Period)

Secondary: Number of participants with protocol defined virologic failure at Week 32 and Week 48 (Maintenance Period)

Secondary: Number of participants with protocol defined virologic failure at Week 32 and Week 48 (Maintenance Period)

Secondary: Absolute value of plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Secondary: Absolute value of plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Secondary: Change from Baseline in plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Secondary: Change from Baseline in plasma HIV-1 RNA at Week 32 and Week 96 (Maintenance Period)

Secondary: Absolute value of CD4+ at Week 32 and Week 96 (Maintenance Period)

Secondary: Absolute value of CD4+ at Week 32 and Week 96 (Maintenance Period)

Secondary: Change from Baseline in CD4+ at Week 32 and Week 96 (Maintenance Period)

Secondary: Change from Baseline in CD4+ at Week 32 and Week 96 (Maintenance Period)

Secondary: Number of Participants With HIV-1 Disease Progression over Week 32 and Week 96 (Maintenance Period)

Secondary: Number of Participants With HIV-1 Disease Progression over Week 32 and Week 96 (Maintenance Period)

Secondary: Number of Participants With AEs by their Severity Grades over Week 96 (Maintenance Period)

Secondary: Number of Participants With AEs by their Severity Grades over Week 96 (Maintenance Period)

Secondary: Number of Participants With AEs by their Severity Grades over Week 32 (Maintenance Period)

Secondary: Number of Participants With AEs by their Severity Grades over Week 32 (Maintenance Period)

Secondary: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST and CK at Week 32 and Week 96 (Maintenance Period)