TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

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ClinicalTrials.gov Identifier: NCT00540449

Recruitment Status : Completed

First Posted : October 8, 2007

Results First Posted : July 11, 2011

Last Update Posted : March 29, 2016

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Tibotec Pharmaceuticals, Ireland

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions	HIV Infections HIV-1 Human Immunodeficiency Virus Type 1
Interventions	Drug: TMC278 Drug: Efavirenz
Enrollment	694

Participant Flow

Recruitment Details	One hundred and twelve sites in 21 countries randomized participants. In total, 694 participants were randomized: four participants did not start treatment and 690 participants started treatment (346 in the TMC278 group and 344 in the efavirenz [control ] group).
Pre-assignment Details


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Period Title: Overall Study
Started	346	344
Completed	262	266
Not Completed	84	78
Reason Not Completed
Adverse Event	12	32
Sponsor's Decision	1	1
Subject Ineligible To Continue The Trial	2	1
Lost to Follow-up	19	17
Subject Non-Compliant	7	5
Subject Reached A Virologic Endpoint	32	8
Withdrawal by Subject	10	10
Other	1	4

Baseline Characteristics

Arm/Group Title		TMC278	Efavirenz	Total
Arm/Group Description		25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.	Total of all reporting groups
Arm/Group Description		25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		346	344	690
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The analysis population included intent to treat (ITT) population defined as all randomized participants who received at least one dose of the study medication.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	346 participants	344 participants	690 participants
	<=18 years	1 0.3%	0 0.0%	1 0.1%
	Between 18 and 65 years	343 99.1%	343 99.7%	686 99.4%
	>=65 years	2 0.6%	1 0.3%	3 0.4%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	346 participants	344 participants	690 participants
		37 (9.68)	36.7 (9.51)	36.8 (9.59)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	346 participants	344 participants	690 participants
	Female	78 22.5%	69 20.1%	147 21.3%
	Male	268 77.5%	275 79.9%	543 78.7%
Region Enroll Measure Type: Number Unit of measure: Participants	Number Analyzed	346 participants	344 participants	690 participants
Africa		32	31	63
Asia		47	51	98
Latin America		60	69	129
USA, Canada, Europe, Australia		207	193	400

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48
Description	Virological response is defined as confirmed plasma viral load less th...
Description	Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
Responder	287	285
Virologic failure	38	15
Discontinued due to Adverse Event (AE)	6	25
Discontinued due to other reason than AE	15	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278, Efavirenz
	Comments	Assuming a response rate of 75% at 48 weeks for both treatment groups, 340 subjects were needed per treatment (TMC278 or EFV) to establish non-inferiority of TMC278 versus EFV with a maximum allowable difference of 12% and a 1-sided significance level of 2.5%, to yield 95% power.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 - EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Significance level was set at 2.5% (one-sided). No adjustment of p-value for multiple comparisons, since there was only single comparison for the primary endpoint.
	Method	Regression, Logistic
	Comments	Logistic regression model included treatment arm as factor and baseline (log10) viral load as covariate.

Method of Estimation	Estimation Parameter	Difference in proportion of response
	Estimated Value	-0.4
	Confidence Interval	95% -5.9 to 5.2
	Estimation Comments	Difference in proportion responders was estimated through the logistic regression model.

2.Secondary Outcome


Title	The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48
Description	The analysis is based on the last observed viral load (VL) data within...
Description	The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
Virologic Response HIV RNA <50 copies/mL at Wk 48	285	281
Virologic Failure	47	24
No Viral Load Data in 48 week window	14	39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278, Efavirenz
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 - EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Logistic regression model included treatment arm as factor and baseline (log10) viral load as covariate.

Method of Estimation	Estimation Parameter	Difference in proportion of response
	Estimated Value	0.3
	Confidence Interval	95% -5.4 to 5.9
	Estimation Comments	Difference in proportion responders was estimated through the logistic regression model.

3.Secondary Outcome


Title	Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
Responder	263	271
Virologic failure	45	16
Death	0	3
Discontinued due to AE	10	29
Discontinued due to other reason than AE	28	25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278, Efavirenz
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 - EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

Statistical Test of Hypothesis	P-Value	0.0055
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Logistic regression model included treatment arm as factor and baseline (log10) viral load as covariate.

Method of Estimation	Estimation Parameter	Difference in proportion of response
	Estimated Value	-3.2
	Confidence Interval	95% -9.4 to 3.1
	Estimation Comments	Difference in proportion responders was estimated through the logistic regression model.

4.Secondary Outcome


Title	The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
Virologic Response, <50 copies/ml	265	268
Virologic failure	54	27
No viral load data in the 96 week window	27	49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC278, Efavirenz
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the lower limit of the 95% 2-sided confidence interval of the difference in proportions (TMC278 - EFV) exceeds -12%, non-inferiority of TMC278 versus EFV can be concluded.

Statistical Test of Hypothesis	P-Value	0.0013
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Logistic regression model included treatment arm as factor and baseline (log10) viral load as covariate.

Method of Estimation	Estimation Parameter	Difference in proportion of response
	Estimated Value	-1.7
	Confidence Interval	95% -8.0 to 4.5
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).
Description	Virological response is defined as (observed) plasma viral load less t...
Description	Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96).
Time Frame	Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit

Outcome Measure Data

Analysis Population Description

Participants with at least 1 Post-Week 96 visit were included in the analysis.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	258	271
Measure Type: Number Unit of Measure: Participants
	245	261

6.Secondary Outcome


Title	Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
	297	293

7.Secondary Outcome


Title	Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Measure Type: Number Unit of Measure: Participants
	273	278

8.Secondary Outcome


Title	Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)
Description	Change from baseline in CD4+ cell count was imputed in case of missing...
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, Week 48, and Week 96

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	346	344
Mean (Standard Deviation) Unit of Measure: cells per microliter
Absolute cell count, Week 48	195.5 (151.7)	181.6 (156.9)
Absolute cell count, Week 96	220.7 (167.1)	226.7 (188.9)
Relative cell count, Week 48	8.6 (5.8)	8.7 (6.0)
Relative cell count, Week 96	10.1 (7.5)	10.2 (7.2)

9.Secondary Outcome


Title	Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure
Description	Virologic failure for the resistance determinations was defined as lac...
Description	Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Time Frame	Week 96

Outcome Measure Data

Analysis Population Description

The ITT analysis set was considered the primary efficacy analysis set. Here "N" (Number of Participants Analyzed) signifies number of Participants who were evaluable (had data) for this outcome measure.


Arm/Group Title	TMC278	Efavirenz
Arm/Group Description:	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description:	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
Overall Number of Participants Analyzed	52	18
Measure Type: Number Unit of Measure: Participants
Any RAM from Extended NNRTI RAMs list	29	9
NNRTI RAM: E138K	18	0
NNRTI RAM: K101E	5	0
NNRTI RAM: Y181C	5	0
NNRTI RAM: V90I	4	0
NNRTI RAM: V189I	4	0
NNRTI RAM: H221Y	4	0
NNRTI RAM: E138Q	3	0
NNRTI RAM: K103N	1	8
Any RAM from IAS-USA N(t)RTI RAMs list	31	5
N(t)RTI RAM: M184I	24	3
N(t)RTI RAM: M184V	7	3
N(t)RTI RAM: K065R	3	0
N(t)RTI RAM: K219E	3	0
N(t)RTI RAM: Y115F	2	0

Adverse Events

Time Frame	Up to a maximum of 160 weeks for participants in the TMC278 treatment group and up to 147 weeks for participants in the efavirenz treatment group.
Adverse Event Reporting Description	Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.

Arm/Group Title	TMC278	Efavirenz
Arm/Group Description	25 milligram (mg) tablet once daily...	600 mg once daily for 96 weeks.
Arm/Group Description	25 milligram (mg) tablet once daily for 96 weeks.	600 mg once daily for 96 weeks.
All-Cause Mortality
	TMC278	Efavirenz
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	TMC278	Efavirenz
	Affected / at Risk (%)	Affected / at Risk (%)
Total	40/346 (11.56%)	43/344 (12.50%)
Blood and lymphatic system disorders
Febrile neutropenia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Agranulocytosis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Splenic lesion ^* 1	1/346 (0.29%)	0/344 (0.00%)
Cardiac disorders
Atrial flutter ^* 1	0/346 (0.00%)	1/344 (0.29%)
Tachycardia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Coronary artery disease ^* 1	1/346 (0.29%)	0/344 (0.00%)
Congenital, familial and genetic disorders
Thyroglossal cyst ^* 1	0/346 (0.00%)	1/344 (0.29%)
Pyloric stenosis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Gastrointestinal disorders
Haematemesis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Peritoneal haemorrhage ^* 1	1/346 (0.29%)	0/344 (0.00%)
Anal inflammation ^* 1	0/346 (0.00%)	1/344 (0.29%)
Diarrhoea ^* 1	0/346 (0.00%)	1/344 (0.29%)
Gastrointestinal haemorrhage ^* 1	0/346 (0.00%)	1/344 (0.29%)
Nausea ^* 1	0/346 (0.00%)	1/344 (0.29%)
Vomiting ^* 1	0/346 (0.00%)	1/344 (0.29%)
Abdominal pain ^* 1	1/346 (0.29%)	0/344 (0.00%)
Anal fissure ^* 1	1/346 (0.29%)	0/344 (0.00%)
General disorders
Chest pain ^* 1	1/346 (0.29%)	0/344 (0.00%)
Adverse drug reaction ^* 1	0/346 (0.00%)	1/344 (0.29%)
Pelvic mass ^* 1	0/346 (0.00%)	1/344 (0.29%)
Pyrexia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Hepatobiliary disorders
Cholecystitis acute ^* 1	1/346 (0.29%)	0/344 (0.00%)
Cholelithiasis ^* 1	1/346 (0.29%)	1/344 (0.29%)
Cholecystitis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Liver disorder ^* 1	1/346 (0.29%)	0/344 (0.00%)
Immune system disorders
Anaphylactic reaction ^* 1	0/346 (0.00%)	1/344 (0.29%)
Infections and infestations
Abscess limb ^* 1	1/346 (0.29%)	1/344 (0.29%)
Anogenital warts ^* 1	1/346 (0.29%)	0/344 (0.00%)
Appendicitis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Bacterial infection ^* 1	1/346 (0.29%)	0/344 (0.00%)
Bronchiectasis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Cellulitis ^* 1	2/346 (0.58%)	0/344 (0.00%)
Diverticulitis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Helicobacter gastritis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Herpes zoster ^* 1	1/346 (0.29%)	0/344 (0.00%)
Lobar pneumonia ^* 1	1/346 (0.29%)	0/344 (0.00%)
Neurosyphilis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Pneumonia ^* 1	3/346 (0.87%)	2/344 (0.58%)
Sepsis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Syphilis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Arthritis bacterial ^* 1	0/346 (0.00%)	1/344 (0.29%)
Bronchitis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Cerebral toxoplasmosis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Gastroenteritis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Streptococcal bacteraemia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Tuberculous pleurisy ^* 1	0/346 (0.00%)	1/344 (0.29%)
Upper respiratory tract infection ^* 1	0/346 (0.00%)	1/344 (0.29%)
Bone tuberculosis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Folliculitis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Meningococcal sepsis ^* 1	0/346 (0.00%)	1/344 (0.29%)
Mycobacterium avium complex infection ^* 1	1/346 (0.29%)	0/344 (0.00%)
Osteomyelitis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Papilloma viral infection ^* 1	0/346 (0.00%)	1/344 (0.29%)
Respiratory tract infection ^* 1	0/346 (0.00%)	1/344 (0.29%)
Tuberculosis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Injury, poisoning and procedural complications
Alcohol poisoning ^* 1	1/346 (0.29%)	0/344 (0.00%)
Overdose ^* 1	1/346 (0.29%)	0/344 (0.00%)
Drug toxicity ^* 1	0/346 (0.00%)	1/344 (0.29%)
Ankle fracture ^* 1	1/346 (0.29%)	0/344 (0.00%)
Concussion ^* 1	0/346 (0.00%)	1/344 (0.29%)
Facial bones fracture ^* 1	0/346 (0.00%)	1/344 (0.29%)
Injury ^* 1	1/346 (0.29%)	0/344 (0.00%)
Jaw fracture ^* 1	0/346 (0.00%)	1/344 (0.29%)
Poisoning ^* 1	1/346 (0.29%)	0/344 (0.00%)
Sternal fracture ^* 1	1/346 (0.29%)	0/344 (0.00%)
Investigations
Alanine aminotransferase increased ^* 1	0/346 (0.00%)	2/344 (0.58%)
Aspartate aminotransferase increased ^* 1	0/346 (0.00%)	1/344 (0.29%)
Blood alkaline phosphatase increased ^* 1	0/346 (0.00%)	1/344 (0.29%)
Transaminases increased ^* 1	0/346 (0.00%)	1/344 (0.29%)
Metabolism and nutrition disorders
Anorexia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	1/346 (0.29%)	0/344 (0.00%)
Joint swelling ^* 1	1/346 (0.29%)	0/344 (0.00%)
Spondylitis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Back pain ^* 1	0/346 (0.00%)	1/344 (0.29%)
Intervertebral disc protrusion ^* 1	0/346 (0.00%)	1/344 (0.29%)
Spinal osteoarthritis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer ^* 1	1/346 (0.29%)	0/344 (0.00%)
Haemangioma ^* 1	1/346 (0.29%)	0/344 (0.00%)
Kaposi's sarcoma ^* 1	1/346 (0.29%)	0/344 (0.00%)
Uterine leiomyoma ^* 1	1/346 (0.29%)	1/344 (0.29%)
Anal cancer stage 0 ^* 1	0/346 (0.00%)	1/344 (0.29%)
Burkitt's lymphoma ^* 1	2/346 (0.58%)	2/344 (0.58%)
Anal cancer ^* 1	0/346 (0.00%)	1/344 (0.29%)
Hepatic neoplasm ^* 1	0/346 (0.00%)	1/344 (0.29%)
Hepatic neoplasm malignant ^* 1	0/346 (0.00%)	1/344 (0.29%)
Nervous system disorders
Miller fisher syndrome ^* 1	1/346 (0.29%)	0/344 (0.00%)
Cerebral ischaemia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Cerebrovascular accident ^* 1	0/346 (0.00%)	1/344 (0.29%)
Coma ^* 1	0/346 (0.00%)	1/344 (0.29%)
Headache ^* 1	1/346 (0.29%)	1/344 (0.29%)
Sciatica ^* 1	0/346 (0.00%)	1/344 (0.29%)
Psychiatric disorders
Alcoholism ^* 1	1/346 (0.29%)	0/344 (0.00%)
Depression ^* 1	2/346 (0.58%)	2/344 (0.58%)
Drug dependence ^* 1	1/346 (0.29%)	0/344 (0.00%)
Major depression ^* 1	1/346 (0.29%)	0/344 (0.00%)
Suicide attempt ^* 1	1/346 (0.29%)	0/344 (0.00%)
Bipolar disorder ^* 1	0/346 (0.00%)	1/344 (0.29%)
Homicidal ideation ^* 1	1/346 (0.29%)	1/344 (0.29%)
Acute psychosis ^* 1	1/346 (0.29%)	0/344 (0.00%)
Panic attack ^* 1	0/346 (0.00%)	1/344 (0.29%)
Psychotic disorder ^* 1	0/346 (0.00%)	2/344 (0.58%)
Suicidal ideation ^* 1	3/346 (0.87%)	1/344 (0.29%)
Renal and urinary disorders
Calculus ureteric ^* 1	1/346 (0.29%)	0/344 (0.00%)
Glomerulonephritis membranous ^* 1	1/346 (0.29%)	0/344 (0.00%)
Reproductive system and breast disorders
Cystocele ^* 1	1/346 (0.29%)	0/344 (0.00%)
Uterovaginal prolapse ^* 1	1/346 (0.29%)	0/344 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma ^* 1	1/346 (0.29%)	0/344 (0.00%)
Dyspnoea ^* 1	0/346 (0.00%)	1/344 (0.29%)
Pneumothorax ^* 1	1/346 (0.29%)	1/344 (0.29%)
Pulmonary embolism ^* 1	0/346 (0.00%)	1/344 (0.29%)
Asphyxia ^* 1	0/346 (0.00%)	1/344 (0.29%)
Skin and subcutaneous tissue disorders
Erythema ^* 1	1/346 (0.29%)	0/344 (0.00%)
Rash generalised ^* 1	0/346 (0.00%)	1/344 (0.29%)
Surgical and medical procedures
Bowel preparation ^* 1	0/346 (0.00%)	1/344 (0.29%)
Drug rehabilitation ^* 1	0/346 (0.00%)	1/344 (0.29%)
Vascular disorders
Circulatory collapse ^* 1	1/346 (0.29%)	0/344 (0.00%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	TMC278	Efavirenz
	Affected / at Risk (%)	Affected / at Risk (%)
Total	231/346 (66.76%)	268/344 (77.91%)
Gastrointestinal disorders
Nausea ^* 1	44/346 (12.72%)	38/344 (11.05%)
Diarrhoea ^* 1	51/346 (14.74%)	61/344 (17.73%)
Vomiting ^* 1	15/346 (4.34%)	21/344 (6.10%)
General disorders
Fatigue ^* 1	20/346 (5.78%)	31/344 (9.01%)
Infections and infestations
Upper respiratory tract infection ^* 1	53/346 (15.32%)	51/344 (14.83%)
Nasopharyngitis ^* 1	45/346 (13.01%)	44/344 (12.79%)
Influenza ^* 1	37/346 (10.69%)	34/344 (9.88%)
Syphilis ^* 1	22/346 (6.36%)	15/344 (4.36%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	15/346 (4.34%)	20/344 (5.81%)
Back pain ^* 1	23/346 (6.65%)	24/344 (6.98%)
Nervous system disorders
Headache ^* 1	50/346 (14.45%)	44/344 (12.79%)
Dizziness ^* 1	28/346 (8.09%)	91/344 (26.45%)
Somnolence ^* 1	14/346 (4.05%)	24/344 (6.98%)
Psychiatric disorders
Abnormal dreams ^* 1	29/346 (8.38%)	41/344 (11.92%)
Insomnia ^* 1	36/346 (10.40%)	39/344 (11.34%)
Depression ^* 1	25/346 (7.23%)	21/344 (6.10%)
Anxiety ^* 1	9/346 (2.60%)	27/344 (7.85%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	23/346 (6.65%)	20/344 (5.81%)
Skin and subcutaneous tissue disorders
Rash ^* 1	26/346 (7.51%)	42/344 (12.21%)
Pruritus ^* 1	8/346 (2.31%)	18/344 (5.23%)
Vascular disorders
Hypertension ^* 1	21/346 (6.07%)	18/344 (5.23%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA 11.0

Limitations and Caveats

[Not Specified]

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Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Medical Leader
Organization:	Janssen Infectious Diseases BVBA
EMail:	ClinicalTrialDisclosure@its.jnj.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rimsky L, Van Eygen V, Hoogstoel A, Stevens M, Boven K, Picchio G, Vingerhoets J. 96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials. Antivir Ther. 2013;18(8):967-77. doi: 10.3851/IMP2636. Epub 2013 May 28.

Nelson M, Amaya G, Clumeck N, Arns da Cunha C, Jayaweera D, Junod P, Li T, Tebas P, Stevens M, Buelens A, Vanveggel S, Boven K; ECHO and THRIVE Study Groups. Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials. J Antimicrob Chemother. 2012 Aug;67(8):2020-8. doi: 10.1093/jac/dks130. Epub 2012 Apr 24.

Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.

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Responsible Party:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00540449
Obsolete Identifiers:	NCT00613639
Other Study ID Numbers:	CR002689 TMC278-TIDP6-C209 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
First Submitted:	October 4, 2007
First Posted:	October 8, 2007
Results First Submitted:	June 14, 2011
Results First Posted:	July 11, 2011
Last Update Posted:	March 29, 2016

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