A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines

• Sponsor: Tibotec Pharmaceuticals, Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00110305
• Collaborator: (none)
• Enrollment: 368
• Locations: 44
• Arms: 4
• Duration (Months): 78
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the dose-response relationship of antiviral activity after 48 weeks treatment with 3 different dose regimens of TMC278.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus Type 1	Drug: TMC278 25 mg; Drug: TMC278 75 mg; Drug: TMC278 150 mg; Drug: Efavirenz; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)	Phase 2

Detailed Description

This is a randomized (the study medication is assigned by chance), active controlled (participants are assigned to either a recognized effective treatment or the study medication) study. This study consists of 3 phases: screening phase (4 weeks), treatment phase (96 weeks), and follow up phase (4 weeks). In the treatment phase, participants will be randomly assigned to 1 of the 4 treatment groups: (1) TMC278 25 mg, (2) TMC278 75 mg, (3) TMC278 150 mg, or (4) efavirnez (control group); along with investigator selected 2 non-nucleoside reverse transcriptase inhibitor (NRTIs) until Week 96. TMC278 will be assigned by double-blinded fashion (participant and investigator are not aware of the TMC278 dose what participants will receive) and efavirnez will be assigned by open-label fashion (all people know what treatment participants will receive). After Week 96, 3 optional open-label (all people know the identity of the intervention) extension periods will be conducted to collect long term safety and effectiveness data of TMC278. 3 optional extension periods are: first optional extension period (all participants will receive TMC278 75 mg + 2 NRTIs from Week 96 to Week144); second optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 144 to Week 240); and third optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 240 until TMC278 is commercially available). Participants on efavirenz group will have the option to continue on efavirenz + 2 NRTIs until the total treatment duration of 240 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The maximum duration of the study will be 104, 152, or 248 weeks, plus the optional third extension period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIb Randomized, Partially Blinded, Dose-Finding Trial of TMC278 in Antiretroviral-Naive HIV-1 Infected Subjects
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC278 25 mg Participants will receive TMC278 25 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.	Drug: TMC278 25 mg; TMC278 25 mg tablet will be administered once daily.; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs); Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.; Other Names: Combivir Truvada
Experimental: TMC278 75 mg Participants will receive TMC278 75 mg once daily up to Week 144. Later on, participants will receive TMC278 25 mg once daily up to Week 240.	Drug: TMC278 75 mg; TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs); Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.; Other Names: Combivir Truvada
Experimental: TMC278 150 mg Participants will receive TMC278 150 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.	Drug: TMC278 150 mg; TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs); Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.; Other Names: Combivir Truvada
Active Comparator: Efavirenz Participants will receive efavirenz 600 mg once daily up to Week 96. Later on, participants will have an option to continue on efavirenz until Week 144 or until Week 240.	Drug: Efavirenz; Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.; Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs); Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.; Other Names: Combivir Truvada

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [Week 48]

   The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

Secondary Outcome Measures

1. Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [Week 96]

   The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

2. Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis [Week 96]

   The analysis is based on the last observed viral load data within the Week 96 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.

3. Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [Week 240]

   The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

4. Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis [Week 240]

   The analysis is based on the last observed viral load data within the Week 240 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.

5. Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [Week 240]

   The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

6. Change From Baseline in CD4+ Cell Count (Absolute) at Week 96 [Baseline (Day 1 of Week 0) to Week 96]

   Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

7. Change From Baseline in CD4+ Cell Count (Relative) at Week 96 [Baseline (Day 1 of Week 0) to Week 96]

   Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

8. Change From Baseline in CD4+ Cell Count (Absolute) at Week 240 [Baseline (Day 1 of Week 0) to Week 240]

   Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

9. Change From Baseline in CD4+ Cell Count (Relative) at Week 240 [Baseline (Day 1 of week 0) to Week 240]

   Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.

10. Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure [Week 240]

    Virologic failure for the resistance determinations was defined as a viral load greater than 0.5 log10 copies /mL above the nadir with a minimum of 500 copies/mL. For this study, treatment-emergent mutations (for at least one treatment) are presented as Resistance associated mutation (RAMs): i) Non-nucleotide reverse transcriptase inhibitor (NNRTI) RAMs, ii) Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).

11. Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278 [Up to Week 96]

    For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96.

12. Trough Plasma Concentration (Ctrough) for TMC278 [Up to Week 96]

    For each participant, a single value for trough (i.e. predose) plasma concentration (Ctrough) of TMC278 was estimated from a population pharmacokinetic model, based on samples collected throughout the trial up to Week 96.

13. Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles [Up to Week 96]

    Quartile 1, 2, 3 and 4 of AUC24h means the quartile with the lowest 25%, 26-50%, 51-75% and the highest 25% of AUC24h values, respectively, irrespective of the different doses of TMC278. For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96. Virologic response was calculated by time to loss of virologic response (TLOVR) algorithm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented human immunodeficiency virus type 1 (HIV-1) infection

• Never been treated with an antiretroviral (ARV) treatment or therapeutic HIV vaccine, or received less than or equal to 2 weeks treatment prior to screening with an nucleoside reverse transcriptase inhibitors

• HIV-1 plasma viral load above 5000 HIV-1 RNA copies per milliliter, at screening

• Cortisol of at least 550 nano moles per liter (19.9 microgram per deciliter) at screening

• Sensitivity to investigator selected nucleosides, at screening

Exclusion Criteria:

• Currently having active Acquired Immunodeficiency Syndrome (AIDS) defining illness

• Known or suspected acute (primary) HIV-1 infection

• Any current or history of adrenal disorder, and an acute hepatitis A, B, or C infection

• Documented genotypic evidence of Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) resistance at screening

• Pregnant or breastfeeding females

• Not agree to protocol-defined effective use of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beverly Hills	California	United States
2		Washington	District of Columbia	United States
3		Orlando	Florida	United States
4		Tampa	Florida	United States
5		Atlanta	Georgia	United States
6		Stony Brook	New York	United States
7		Winston-Salem	North Carolina	United States
8		Addison	Texas	United States
9		Seattle	Washington	United States
10		Buenos Aires		Argentina
11		Rosario		Argentina
12		Wien		Austria
13		Campinas		Brazil
14		Curitiba		Brazil
15		Pinheiros		Brazil
16		Rio De Janeiro		Brazil
17		Sao Paulo		Brazil
18		Beijing		China
19		Paris Cedex 10		France
20		Paris Cedex 12		France
21		Paris		France
22		Tourcoing		France
23		Berlin		Germany
24		Freiburg		Germany
25		Köln		Germany
26		München		Germany
27		Ciudad De Mexico		Mexico
28		San Juan		Puerto Rico
29		Kazan		Russian Federation
30		Moscow N/A		Russian Federation
31		Moscow		Russian Federation
32		Nizhny Novgorod		Russian Federation
33		Saint-Petersburg		Russian Federation
34		St Petersburg		Russian Federation
35		Volgograd		Russian Federation
36		Bloemfontein		South Africa
37		Cape Town		South Africa
38		Johannesburg		South Africa
39		Bangkok		Thailand
40		Chiang Mai		Thailand
41		Khon Kaen		Thailand
42		Kampala		Uganda
43		London		United Kingdom
44		Manchester		United Kingdom

Sponsors and Collaborators

• Tibotec Pharmaceuticals, Ireland

Investigators

• Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial, Tibotec Pharmaceuticals, Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tibotec Pharmaceuticals, Ireland
• ClinicalTrials.gov Identifier: NCT00110305
• Other Study ID Numbers: CR006760; TMC278-C204; R278474-C204; NCT00980837
• First Posted: May 6, 2005
• Last Update Posted: Jun 25, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Tibotec Pharmaceuticals, Ireland: Human Immunodeficiency Virus Type 1; Human immunodeficiency virus (HIV); Antiretroviral; Antiviral; ARV; TMC278; Efavirenz; Combivir; Truvada; Zidovudine; Lamivudine; Tenofovir disoproxil fumarate; Emtricitabine
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Efavirenz; Reverse Transcriptase Inhibitors; Rilpivirine

Study Results

Participant Flow

Recruitment Details	368 participants were enrolled at multiple centers in different countries.
Pre-assignment Detail	368 participants were randomly assigned to 4 treatment groups (TMC278 25 mg: 93; TMC278 75 mg: 95; TMC278 150 mg: 91; and Efavirenz: 89). Participant flow through Week 240 was reported for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Period Title: Overall Study
STARTED	279	89
COMPLETED	165	57
NOT COMPLETED	114	32

Baseline Characteristics

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC 150 mg	Efavirenz	Total
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	Efavirenz 600 mg once daily	Total of all reporting groups
Overall Participants	93	95	91	89	368
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	92 98.9%	95 100%	89 97.8%	89 100%	365 99.2%
>=65 years	1 1.1%	0 0%	2 2.2%	0 0%	3 0.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.7 (8.9)	36.3 (8.3)	35.9 (9.7)	35.4 (8.1)	36.1 (8.75)
Sex: Female, Male (Count of Participants)
Female	28 30.1%	31 32.6%	33 36.3%	29 32.6%	121 32.9%
Male	65 69.9%	64 67.4%	58 63.7%	60 67.4%	247 67.1%
Region Enroll (participants) [Number]
Asia, South Africa and Uganda	32 34.4%	32 33.7%	31 34.1%	29 32.6%	124 33.7%
Europe, USA and Russia	33 35.5%	33 34.7%	32 35.2%	32 36%	130 35.3%
Latin America	28 30.1%	30 31.6%	28 30.8%	28 31.5%	114 31%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Description	The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication.

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC278 150 mg	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	Efaviren 600 mg once daily
Measure Participants	93	95	91	279	89
Number [Participants]	74 79.6%	76 80%	70 76.9%	220 247.2%	72 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278 25 mg, TMC278 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and Nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Differences in response rate
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -10.4 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC278 25 mg, TMC278 150 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -13.6 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	TMC278 75 mg, TMC278 150 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -14.0 to 8.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	All TMC278, Efavirenz
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -10.5 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Description	The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication.

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC278 150 mg	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	93	95	91	279	89
Number [Participants]	71 76.3%	68 71.6%	65 71.4%	204 229.2%	63 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278 25 mg, TMC278 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and Nucleoside/tide reverse transcriptase inhibitors (N[t]RTIs) used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -17.1 to 7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC278 25 mg, TMC278 150 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -17.3 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	TMC278 75 mg, TMC278 150 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -12.9 to 12.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	All TMC278, Efavirenz
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	The significance level for each comparison was 5% (two-sided). No further adjustment of this significance level was applied.
	Method	Regression, Logistic
	Comments	This model with factors treatment, region, and N(t)RTIs used, and baseline viral load as covariate.
Method of Estimation	Estimation Parameter	Differences in response
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -8.1 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Description	The analysis is based on the last observed viral load data within the Week 96 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication.

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC278 150 mg	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	93	95	91	279	89
Number [Participants]	71 76.3%	70 73.7%	66 72.5%	207 232.6%	64 17.4%

4. Secondary Outcome

Title	Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Description	The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	89
Number [Participants]	152 163.4%	51 53.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278 25 mg, TMC278 75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	-2.8
	Confidence Interval	() 95%; -14.7 to 9.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Description	The analysis is based on the last observed viral load data within the Week 240 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	89
Number [Participants]	150 161.3%	51 53.7%

6. Secondary Outcome

Title	Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Description	The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	89
Number [Participants]	166 178.5%	54 56.8%

7. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count (Absolute) at Week 96
Description	Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame	Baseline (Day 1 of Week 0) to Week 96

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication.Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count.

Arm/Group Title	TMC278 25mg	TMC278 75 mg	TMC278 150 mg	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	93	95	91	279	88
Mean (Standard Deviation) [Cells per microliter]	145.9 (117.0)	172.0 (156.5)	158.9 (156.5)	159.0 (144.4)	159.8 (125.7)

8. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count (Relative) at Week 96
Description	Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame	Baseline (Day 1 of Week 0) to Week 96

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count.

Arm/Group Title	TMC278 25mg	TMC278 75 mg	TMC278 150 mg	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	93	95	91	279	88
Mean (Standard Deviation) [Percentage of CD4+ Cells]	8.6 (6.9)	9.9 (7.3)	9.3 (7.1)	9.3 (7.1)	9.6 (7.0)

9. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count (Absolute) at Week 240
Description	Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame	Baseline (Day 1 of Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

ITT population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	88
Mean (Standard Deviation) [Cells per microliter]	221.0 (227.2)	217.9 (213.7)

10. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count (Relative) at Week 240
Description	Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Time Frame	Baseline (Day 1 of week 0) to Week 240

Outcome Measure Data

Analysis Population Description

ITT population: Participants who received at least 1 dose of study medication. Efavirenz group, 1 participant was excluded due to missing baseline CD4+ cell count. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	88
Mean (Standard Deviation) [Percentage of CD4+ cells]	8.7 (8.7)	9.7 (9.1)

11. Secondary Outcome

Title	Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Description	Virologic failure for the resistance determinations was defined as a viral load greater than 0.5 log10 copies /mL above the nadir with a minimum of 500 copies/mL. For this study, treatment-emergent mutations (for at least one treatment) are presented as Resistance associated mutation (RAMs): i) Non-nucleotide reverse transcriptase inhibitor (NNRTI) RAMs, ii) Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Time Frame	Week 240

Outcome Measure Data

Analysis Population Description

Intent to treat population: Participants who received at least 1 dose of study medication. This was measured at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Arm/Group Title	All TMC278	Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	Efavirenz 600 mg once daily
Measure Participants	279	89
Treatment-emergent NNRTI RAM	17 18.3%	4 4.2%
E138K	7 7.5%	0 0%
K101E	6 6.5%	0 0%
K103N	1 1.1%	3 3.2%
Treatment-emergent N(t)RTI RAM	13 14%	0 0%
M184V	10 10.8%	0 0%

12. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278
Description	For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Analysis included participants with sufficient number of pharmacokinetic samples in order to derive population pharmacokinetic parameter.

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC278 150 mg
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily
Measure Participants	89	93	87
Mean (Standard Deviation) [ng*h/mL]	2767 (1166)	5906 (2419)	10281 (4208)

13. Secondary Outcome

Title	Trough Plasma Concentration (Ctrough) for TMC278
Description	For each participant, a single value for trough (i.e. predose) plasma concentration (Ctrough) of TMC278 was estimated from a population pharmacokinetic model, based on samples collected throughout the trial up to Week 96.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Analysis included participants with sufficient number of pharnacokintetic samples in order to derive population pharmacokinetic parameter.

Arm/Group Title	TMC278 25 mg	TMC278 75 mg	TMC278 150 mg
Arm/Group Description	TMC278 25 mg once daily	TMC278 75 mg once daily	TMC278 150 mg once daily
Measure Participants	89	93	87
Mean (Standard Deviation) [ng/mL]	92.7 (45.2)	196.0 (90.1)	342.0 (154.0)

14. Secondary Outcome

Title	Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles
Description	Quartile 1, 2, 3 and 4 of AUC24h means the quartile with the lowest 25%, 26-50%, 51-75% and the highest 25% of AUC24h values, respectively, irrespective of the different doses of TMC278. For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96. Virologic response was calculated by time to loss of virologic response (TLOVR) algorithm.
Time Frame	Up to Week 96

Outcome Measure Data

Analysis Population Description

Analysis included participants who received TMC278 with sufficient number of pharnacokintetic samples in order to derive population pharmacokinetic parameter. Participants who discontinued treatment for reasons other than virological failure were excluded from this analysis.

Arm/Group Title	AUC24h Quartile 1	AUC24h Quartile 2	AUC24h Quartile 3	AUC24h Quartile 4
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily	TMC278 25 mg, 75 mg, and 150 mg once daily
Measure Participants	58	54	59	56
Number [Participants]	48 51.6%	50 52.6%	55 60.4%	51 57.3%

Adverse Events

Time Frame	Up to 336 weeks for participants in the TMC278 treatment group and up to 260 weeks for participants in the efavirenz treatment group.
Adverse Event Reporting Description	Adverse events were reported at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.
Arm/Group Title	All TMC278		Efavirenz
Arm/Group Description	TMC278 25 mg, 75 mg, and 150 mg once daily		Efavirenz 600 mg once daily
All Cause Mortality
	All TMC278		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	All TMC278		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/279 (17.6%)		17/89 (19.1%)
Blood and lymphatic system disorders
Anaemia	5/279 (1.8%)		0/89 (0%)
Leukopenia	1/279 (0.4%)		0/89 (0%)
Neutropenia	1/279 (0.4%)		0/89 (0%)
Cardiac disorders
Acute myocardial infarction	1/279 (0.4%)		0/89 (0%)
Angina unstable	1/279 (0.4%)		0/89 (0%)
Supraventricular tachycardia	1/279 (0.4%)		0/89 (0%)
Gastrointestinal disorders
Abdominal pain	1/279 (0.4%)		0/89 (0%)
Anal fissure	1/279 (0.4%)		0/89 (0%)
Anal fistula	2/279 (0.7%)		0/89 (0%)
Appendicitis perforated	1/279 (0.4%)		0/89 (0%)
Colitis	0/279 (0%)		1/89 (1.1%)
Constipation	1/279 (0.4%)		0/89 (0%)
Diarrhoea haemorrhagic	0/279 (0%)		1/89 (1.1%)
Intestinal infarction	1/279 (0.4%)		0/89 (0%)
Intestinal obstruction	1/279 (0.4%)		0/89 (0%)
Pancreatitis	1/279 (0.4%)		0/89 (0%)
Pancreatitis acute	1/279 (0.4%)		0/89 (0%)
Peritonitis	0/279 (0%)		1/89 (1.1%)
Rectal haemorrhage	1/279 (0.4%)		0/89 (0%)
General disorders
Chest pain	1/279 (0.4%)		0/89 (0%)
Death	1/279 (0.4%)		0/89 (0%)
Pyrexia	2/279 (0.7%)		0/89 (0%)
Hepatobiliary disorders
Bile duct stone	1/279 (0.4%)		0/89 (0%)
Cholecystitis acute	1/279 (0.4%)		0/89 (0%)
Cholelithiasis	1/279 (0.4%)		0/89 (0%)
Cytolytic hepatitis	1/279 (0.4%)		0/89 (0%)
Hepatitis	1/279 (0.4%)		0/89 (0%)
Hepatitis acute	0/279 (0%)		1/89 (1.1%)
Hydrocholecystis	1/279 (0.4%)		0/89 (0%)
Infections and infestations
Abscess neck	1/279 (0.4%)		0/89 (0%)
Appendicitis	0/279 (0%)		1/89 (1.1%)
Arthritis bacterial	1/279 (0.4%)		0/89 (0%)
Cellulitis	0/279 (0%)		1/89 (1.1%)
Clostridial infection	1/279 (0.4%)		1/89 (1.1%)
Cytomegalovirus colitis	1/279 (0.4%)		0/89 (0%)
Hepatitis C	0/279 (0%)		1/89 (1.1%)
Implant site infection	1/279 (0.4%)		0/89 (0%)
Lobar pneumonia	1/279 (0.4%)		1/89 (1.1%)
Lung infection	1/279 (0.4%)		0/89 (0%)
Malaria	0/279 (0%)		1/89 (1.1%)
Meningitis tuberculous	1/279 (0.4%)		0/89 (0%)
Oral candidiasis	1/279 (0.4%)		0/89 (0%)
Osteomyelitis	1/279 (0.4%)		0/89 (0%)
Perianal abscess	1/279 (0.4%)		0/89 (0%)
Pneumonia	3/279 (1.1%)		0/89 (0%)
Pneumonia streptococcal	1/279 (0.4%)		0/89 (0%)
Respiratory tract infection	1/279 (0.4%)		0/89 (0%)
Sepsis syndrome	1/279 (0.4%)		0/89 (0%)
Septic shock	1/279 (0.4%)		0/89 (0%)
Subcutaneous abscess	0/279 (0%)		2/89 (2.2%)
Injury, poisoning and procedural complications
Ankle fracture	1/279 (0.4%)		0/89 (0%)
Brain contusion	1/279 (0.4%)		0/89 (0%)
Drug toxicity	1/279 (0.4%)		0/89 (0%)
Humerus fracture	0/279 (0%)		1/89 (1.1%)
Muscle injury	0/279 (0%)		1/89 (1.1%)
Road traffic accident	1/279 (0.4%)		1/89 (1.1%)
Investigations
Alanine aminotransferase increased	1/279 (0.4%)		0/89 (0%)
Aspartate aminotransferase increased	1/279 (0.4%)		0/89 (0%)
Blood amylase increased	1/279 (0.4%)		1/89 (1.1%)
Metabolism and nutrition disorders
Anorexia	1/279 (0.4%)		0/89 (0%)
Dehydration	1/279 (0.4%)		0/89 (0%)
Diabetes mellitus	1/279 (0.4%)		0/89 (0%)
Metabolic acidosis	1/279 (0.4%)		0/89 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/279 (0%)		1/89 (1.1%)
Back pain	1/279 (0.4%)		0/89 (0%)
Costochondritis	1/279 (0.4%)		0/89 (0%)
Lumbar spinal stenosis	1/279 (0.4%)		0/89 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma	2/279 (0.7%)		0/89 (0%)
Cervix cancer metastatic	1/279 (0.4%)		1/89 (1.1%)
Chondrosarcoma metastatic	0/279 (0%)		1/89 (1.1%)
Kaposi's sarcoma	1/279 (0.4%)		0/89 (0%)
Lymphoma	2/279 (0.7%)		0/89 (0%)
Squamous cell carcinoma	1/279 (0.4%)		0/89 (0%)
Uterine leiomyoma	1/279 (0.4%)		0/89 (0%)
Nervous system disorders
Epilepsy	1/279 (0.4%)		0/89 (0%)
Headache	0/279 (0%)		1/89 (1.1%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/279 (0%)		1/89 (1.1%)
Psychiatric disorders
Depression	1/279 (0.4%)		0/89 (0%)
Intentional self-injury	1/279 (0.4%)		0/89 (0%)
Major depression	1/279 (0.4%)		0/89 (0%)
Suicide attempt	1/279 (0.4%)		0/89 (0%)
Renal and urinary disorders
Renal failure	1/279 (0.4%)		0/89 (0%)
Renal impairment	1/279 (0.4%)		0/89 (0%)
Reproductive system and breast disorders
Ovarian cyst	1/279 (0.4%)		0/89 (0%)
Prostatitis	0/279 (0%)		1/89 (1.1%)
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic	1/279 (0.4%)		0/89 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/279 (0.4%)		0/89 (0%)
Surgical and medical procedures
Ovarian cystectomy	1/279 (0.4%)		0/89 (0%)
Penile prosthesis insertion	1/279 (0.4%)		0/89 (0%)
Vascular disorders
Arterial occlusive disease	1/279 (0.4%)		0/89 (0%)
Deep vein thrombosis	0/279 (0%)		1/89 (1.1%)
Other (Not Including Serious) Adverse Events
	All TMC278		Efavirenz
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	241/279 (86.4%)		82/89 (92.1%)
Blood and lymphatic system disorders
Anaemia	24/279 (8.6%)		2/89 (2.2%)
Ear and labyrinth disorders
Vertigo	4/279 (1.4%)		10/89 (11.2%)
Eye disorders
Conjunctivitis	9/279 (3.2%)		5/89 (5.6%)
Gastrointestinal disorders
Abdominal pain	20/279 (7.2%)		4/89 (4.5%)
Abdominal pain upper	13/279 (4.7%)		5/89 (5.6%)
Diarrhoea	33/279 (11.8%)		16/89 (18%)
Dyspepsia	36/279 (12.9%)		7/89 (7.9%)
Haemorrhoids	10/279 (3.6%)		7/89 (7.9%)
Nausea	100/279 (35.8%)		26/89 (29.2%)
Vomiting	33/279 (11.8%)		11/89 (12.4%)
General disorders
Fatigue	23/279 (8.2%)		4/89 (4.5%)
Pyrexia	19/279 (6.8%)		3/89 (3.4%)
Infections and infestations
Body tinea	4/279 (1.4%)		7/89 (7.9%)
Bronchitis	20/279 (7.2%)		3/89 (3.4%)
Condyloma acuminatum	17/279 (6.1%)		3/89 (3.4%)
Gastroenteritis	11/279 (3.9%)		5/89 (5.6%)
Herpes simplex	25/279 (9%)		7/89 (7.9%)
Herpes zoster	15/279 (5.4%)		4/89 (4.5%)
Influenza	27/279 (9.7%)		8/89 (9%)
Nasopharyngitis	45/279 (16.1%)		19/89 (21.3%)
Pharyngitis	18/279 (6.5%)		4/89 (4.5%)
Respiratory tract infection	9/279 (3.2%)		5/89 (5.6%)
Respiratory tract infection viral	1/279 (0.4%)		7/89 (7.9%)
Rhinitis	12/279 (4.3%)		5/89 (5.6%)
Sinusitis	20/279 (7.2%)		3/89 (3.4%)
Tinea pedis	8/279 (2.9%)		5/89 (5.6%)
Upper respiratory tract infection	49/279 (17.6%)		9/89 (10.1%)
Urinary tract infection	21/279 (7.5%)		6/89 (6.7%)
Investigations
Alanine aminotransferase increased	21/279 (7.5%)		6/89 (6.7%)
Aspartate aminotransferase increased	17/279 (6.1%)		5/89 (5.6%)
Blood cholesterol increased	13/279 (4.7%)		11/89 (12.4%)
Low density lipoprotein increased	16/279 (5.7%)		9/89 (10.1%)
Metabolism and nutrition disorders
Anorexia	19/279 (6.8%)		7/89 (7.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	39/279 (14%)		11/89 (12.4%)
Back pain	31/279 (11.1%)		5/89 (5.6%)
Myalgia	18/279 (6.5%)		3/89 (3.4%)
Nervous system disorders
Dizziness	31/279 (11.1%)		27/89 (30.3%)
Headache	62/279 (22.2%)		15/89 (16.9%)
Somnolence	10/279 (3.6%)		10/89 (11.2%)
Psychiatric disorders
Abnormal dreams	6/279 (2.2%)		5/89 (5.6%)
Depression	19/279 (6.8%)		9/89 (10.1%)
Insomnia	23/279 (8.2%)		6/89 (6.7%)
Nightmare	1/279 (0.4%)		5/89 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	29/279 (10.4%)		12/89 (13.5%)
Skin and subcutaneous tissue disorders
Dry skin	14/279 (5%)		1/89 (1.1%)
Pruritus	18/279 (6.5%)		4/89 (4.5%)
Rash	5/279 (1.8%)		7/89 (7.9%)
Seborrhoeic dermatitis	7/279 (2.5%)		5/89 (5.6%)
Vascular disorders
Hypertension	22/279 (7.9%)		3/89 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.