An Open-label Trial With TMC125 in Patients Who Have Virologically Failed in a DUET Trial (TMC125-C206 or TMC125-C216).

• Sponsor: Tibotec Pharmaceuticals, Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00359021
• Collaborator: (none)
• Enrollment: 503
• Locations: 78
• Arm: 1
• Duration (Months): 67
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the long-term safety and tolerability of TMC125 200 mg twice daily as part of an antiretroviral therapy including TMC114/rtv and an investigator selected optimized background in HIV-1 infected patients who have participated in a DUET trial (TMC125-C206 or TMC125 C216) and have met the definition of virologic failure at Week 24 or later in these trials.

Condition or Disease	Intervention/Treatment	Phase
HIV-1	Drug: TMC125	Phase 3

Detailed Description

This is a Phase III open-label, roll-over trial to evaluate the long term tolerability, safety, antiviral and immunological effect of TMC125 as part of an individually optimized antiretroviral therapy including TMC114/rtv in HIV-1 infected patients who participated in one of the DUET (TMC125-C206 or TMC125-C216) trials. Also the change in HIV-1 resistance over time will be evaluated. This trial offers patients meeting the definition of virologic failure at Week 24 or beyond the option to roll-over to an open-label trial where they will receive TMC125 and TMC114/rtv. Three hundred patients are estimated to enroll into this trial. The withdrawal visit of the DUET trial will be the first visit of this trial. From this visit onward, all patients will receive 200 mg twice daily TMC125 and 600/100 mg twice daily TMC114/rtv until both TMC114 and TMC125 are commercially available or the therapy is no longer of clinical benefit to the patient. Patients will receive an antiretroviral therapy consisting of TMC125 as the only non-nucleoside reverse transcriptase inhibitor (NNRTI), TMC114/rtv as the only protease inhibitor (PI) and an optimized background, which will be selected by the investigator according to the local standard of care, the patient's experience with previous therapies and most recent resistance testing. The most recent HIV-1 genotype-analysis system report results from the DUET trial will be made available. TMC125 will be dosed at 200 mg twice daily, administered orally as 2 tablets twice daily with food.TMC114/rtv will be dosed at 600/100 mg twice daily, administered orally as 2 tablets TMC114 and 1 capsule ritonavir twice daily with food.The optimized background will comprise of at least 1 approved ARV drug: 1 or more NRTI(s), with or without ENF. Administration will continue until both TMC114 and TMC125 are commercially available or therapy is no longer of clinical benefit to the patient.

Study Design

• Study Type: Interventional
• Actual Enrollment: 503 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Trial With TMC125 as Part of an ART Including TMC114/Rtv and an Investigator-selected OBR in HIV-1 Infected Subjects Who Participated in a DUET Phase III Trial (TMC125-C206 or TMC125-C216).
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 TMC125 200 mg twice daily until commercially available	Drug: TMC125; 200 mg twice daily until commercially available

Outcome Measures

Primary Outcome Measures

1. The Number of Participants Experiencing Adverse Events [1 week to 180 weeks, with a median of 62 weeks]

   The table below provides the number of participants who experienced Serious Adverse Events (SAEs) and Other Adverse Events (except SAEs) that started or worsened in severity during the overall TMC125-C217 treatment period. The duration of treatment ranged per patient from 1 week to 180 weeks, with a median of 62 weeks.

Secondary Outcome Measures

1. The Percentage of Participants With Virologic Outcomes Over Time [Weeks 24, 48, and 96]

   The table below shows the percentage of participants with virologic suppression (< 50 copies/mL), the percentage of participants who were virologic failures (VF) (>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load >50 copies/mL), and the percentage of participants with no viral load (VL) data available over time (ie, at Weeks 24, 48, and 96).

2. Change in Plasma Viral Load Versus Baseline (ie, Mean Change in log10 Plasma Viral Load From Baseline Over Time) [Baseline, Week 24, Week 48, and Week 96]

   In the table below, the total number of participants analyzed in the Duet Placebo and Duet TMC125 groups, respectively at each time point were: Baseline (256;247 participants), Week 24 (251;240 participants), Week 48 (235;192 participants), and Week 96 (123;69 participants).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient was previously randomized in a DUET (TMC125-C206 or TMC125-C216) trial and completed at least 24 weeks of treatment

• Patient was virologically failing in a DUET trial.

Exclusion Criteria:

• Use of disallowed concomitant therapy

• Any grade 4 toxicity according to the Division of AIDS (DAIDS) grading table

• Patients who had to be withdrawn from the DUET (TMC125-C206 or TMC125-C216) trials because of any of the mandatory withdrawal criteria of that trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States
2		Little Rock	Arkansas	United States
3		Beverly Hills	California	United States
4		Long Beach	California	United States
5		Los Angeles	California	United States
6		Palm Springs	California	United States
7		San Diego	California	United States
8		San Francisco	California	United States
9		Denver	Colorado	United States
10		Washington	District of Columbia	United States
11		Fort Laudersale	Florida	United States
12		Ft Lauderdale	Florida	United States
13		Miami	Florida	United States
14		N Miami Beach	Florida	United States
15		Safety Harbor	Florida	United States
16		Tampa	Florida	United States
17		Chicago	Illinois	United States
18		Boston	Massachusetts	United States
19		Camden	New Jersey	United States
20		Newark	New Jersey	United States
21		Bronx	New York	United States
22		New York	New York	United States
23		Durham	North Carolina	United States
24		Winston-Salem	North Carolina	United States
25		Portland	Oregon	United States
26		Philadelphia	Pennsylvania	United States
27		Austin	Texas	United States
28		Dallas	Texas	United States
29		Houston	Texas	United States
30		Longview	Texas	United States
31		Annandale	Virginia	United States
32		Seattle	Washington	United States
33		Buenos Aires		Argentina
34		Cordoba		Argentina
35		Florencio Varela		Argentina
36		Neuquen		Argentina
37		Darlinghurst		Australia
38		Antwerpen		Belgium
39		Liege		Belgium
40		Curitiba		Brazil
41		Rio De Janeiro		Brazil
42		Salvador		Brazil
43		Sao Paulo		Brazil
44		Calgary	Alberta	Canada
45		Toronto	Ontario	Canada
46		Montreal	Quebec	Canada
47		Toronto		Canada
48		Providencia		Chile
49		Santiago		Chile
50		Bordeaux Cedex		France
51		Bordeaux N/A		France
52		Le Kremlin Bicetre		France
53		Lyon		France
54		Marseille Cedex 09		France
55		Paris Cedex 10		France
56		Paris Cedex 12		France
57		Paris Cedex 15		France
58		Paris, 75		France
59		Paris		France
60		Rennes		France
61		Toulouse		France
62		Tourcoing		France
63		Villejuif N/A		France
64		Berlin		Germany
65		Essen		Germany
66		Hamburg		Germany
67		Mannheim		Germany
68		München		Germany
69		Ciudad De Mexico		Mexico
70		Mex Ctity		Mexico
71		Panama		Panama
72		San Juan		Puerto Rico
73		Barcelona N/A		Spain
74		Barcelona		Spain
75		Madrid		Spain
76		Valencia		Spain
77		Bangkok		Thailand
78		Khon Kaen		Thailand

Sponsors and Collaborators

• Tibotec Pharmaceuticals, Ireland

Investigators

• Study Director: Tibotec Pharmaceuticals Clinical Trial, Tibotec Pharmaceutical Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tibotec Pharmaceuticals, Ireland
• ClinicalTrials.gov Identifier: NCT00359021
• Other Study ID Numbers: CR002740; TMC125-C217; TMC125-C206; TMC125-C216
• First Posted: Aug 1, 2006
• Last Update Posted: May 16, 2014
• Last Verified: May 1, 2014

• Keywords provided by Tibotec Pharmaceuticals, Ireland: HIV-1; treatment experienced; virologic failure
• Additional relevant MeSH terms: Etravirine

Study Results

Participant Flow

Pre-assignment Detail	Participants with human immunodeficiency virus - type 1 (HIV-1) infection were enrolled in this study from DUET Study TMC125-C206 or TMC125-C216 and met the definition of virologic failure at Week 24 or later in these studies, or who completed one of the DUET studies after 96 weeks of treatment.

Arm/Group Title	DUET PLACEBO	DUET TMC125
Arm/Group Description	Participants who received Placebo in a previous DUET study and received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.	Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.
Period Title: Overall Study
STARTED	256	247
COMPLETED	175	195
NOT COMPLETED	81	52

Baseline Characteristics

Arm/Group Title	DUET PLACEBO	DUET TMC125	Total
Arm/Group Description	Participants who received Placebo in a previous DUET study and received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.	Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.	Total of all reporting groups
Overall Participants	256	247	503
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	252 98.4%	245 99.2%	497 98.8%
>=65 years	4 1.6%	2 0.8%	6 1.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.9 (8.28)	46.6 (7.01)	46.7 (7.68)
Sex: Female, Male (Count of Participants)
Female	27 10.5%	37 15%	64 12.7%
Male	229 89.5%	210 85%	439 87.3%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants Experiencing Adverse Events
Description	The table below provides the number of participants who experienced Serious Adverse Events (SAEs) and Other Adverse Events (except SAEs) that started or worsened in severity during the overall TMC125-C217 treatment period. The duration of treatment ranged per patient from 1 week to 180 weeks, with a median of 62 weeks.
Time Frame	1 week to 180 weeks, with a median of 62 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis was carried out on the ITT population, which included all participants who received at least one dose of investigational medication.

Arm/Group Title	DUET PLACEBO	DUET TMC125	All Participants
Arm/Group Description	Participants who received Placebo in a previous DUET study received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.	Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.	DUET Placebo + DUET TMC125
Measure Participants	256	247	503
Serious Adverse Events (SAEs)	46 18%	42 17%	88 17.5%
Other Adverse Events (AEs)	160 62.5%	137 55.5%	297 59%

2. Secondary Outcome

Title	The Percentage of Participants With Virologic Outcomes Over Time
Description	The table below shows the percentage of participants with virologic suppression (< 50 copies/mL), the percentage of participants who were virologic failures (VF) (>50 copies/mL, discontinued prior to time X for reasons of VF or for other reasons, except for VF or adverse event, with a last viral load >50 copies/mL), and the percentage of participants with no viral load (VL) data available over time (ie, at Weeks 24, 48, and 96).
Time Frame	Weeks 24, 48, and 96

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was used as the primary analysis population for the efficacy analysis and included all participants who took at least one dose of etravirine (ETR) (also known as TMC125) in the TMC125-C217 study.

Arm/Group Title	DUET PLACEBO	DUET TMC125
Arm/Group Description	Participants who received Placebo in a previous DUET study received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.	Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.
Measure Participants	256	247
Week 24 - Virologic Response (<50 cop/mL)	43.0 16.8%	62.3 25.2%
Week 24 - Virologic Failure	46.9 18.3%	31.6 12.8%
Week 24 - No VL Data available	10.2 4%	6.1 2.5%
Week 48 - Virologic Response (<50 cop/mL)	35.2 13.8%	44.5 18%
Week 48 - Virologic Failure	50.4 19.7%	31.2 12.6%
Week 48 - No VL Data available	14.5 5.7%	24.3 9.8%
Week 96 -Virologic Response (<50 cop/mL)	7.4 2.9%	4.5 1.8%
Week 96 - Virologic Failure	48.0 18.8%	27.5 11.1%
Week 96 - No VL Data available	44.5 17.4%	68.0 27.5%

3. Secondary Outcome

Title	Change in Plasma Viral Load Versus Baseline (ie, Mean Change in log10 Plasma Viral Load From Baseline Over Time)
Description	In the table below, the total number of participants analyzed in the Duet Placebo and Duet TMC125 groups, respectively at each time point were: Baseline (256;247 participants), Week 24 (251;240 participants), Week 48 (235;192 participants), and Week 96 (123;69 participants).
Time Frame	Baseline, Week 24, Week 48, and Week 96

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was used as the primary analysis population for the efficacy analysis and included all participants who took at least one dose of etravirine (ETR) (also known as TMC125) in the TMC125-C217 study.

Arm/Group Title	DUET PLACEBO	DUET TMC125
Arm/Group Description	Participants who received Placebo in a previous DUET study received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.	Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.
Measure Participants	256	247
Week 24	-0.8	0
Week 48	-0.7	-0.1
Week 96	-0.5	-0.2

Adverse Events

Time Frame	07-Jun-2006 to 24-Jan-2012.
Adverse Event Reporting Description	All "Serious Adverse Events (SAEs)" emerging during the TMC125-C217 treatment period are reported below; "Other Adverse Events (not including SAEs)" provided below occurred in at least 0.5% of participants. The duration of the TMC125 treatment period ranged per patient from 1 week to 180 weeks, with a median of 62 weeks.
Arm/Group Title	DUET PLACEBO		DUET TMC125		All Participants
Arm/Group Description	Participants who received Placebo in a previous DUET study and received open-label treatment with 200 mg twice daily etravirine, also known as TMC125 (ETR) and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-naïve participants.		Participants who received etravirine, also known as TMC125 (ETR) in a previous DUET study and received open-label treatment with 200 mg twice daily ETR and 600/100 mg twice daily darunavir (DRV)/low-dose ritonavir (rtv) were referred to as ETR-experienced participants.		Participants who received placebo or TMC125 in a previous DUET study (DUET Placebo + DUET TMC125).
All Cause Mortality
	DUET PLACEBO		DUET TMC125		All Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DUET PLACEBO		DUET TMC125		All Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/256 (18%)		42/247 (17%)		88/503 (17.5%)
Blood and lymphatic system disorders
Anaemia	2/256 (0.8%)		2/247 (0.8%)		4/503 (0.8%)
Febrile bone marrow aplasia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Febrile neutropenia	2/256 (0.8%)		0/247 (0%)		2/503 (0.4%)
Haemorrhagic diathesis	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Pancytopenia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Thrombocytopenia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Thrombotic thrombocytopenic purpura	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Cardiac disorders
Angina unstable	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Atrial fibrillation	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Atrial flutter	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Bradycardia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cardiac failure	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Cardio-respiratory arrest	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cardiopulmonary failure	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Coronary artery disease	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Coronary artery occlusion	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Myocardial infarction	2/256 (0.8%)		2/247 (0.8%)		4/503 (0.8%)
Pericarditis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Gastrointestinal disorders
Abdominal pain	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Ascites	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Colitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Diarrhoea	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Dysphagia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Eructation	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Gastric ulcer	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Haematemesis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Haemorrhoids	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Hernial eventration	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Intestinal polyp	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Mesenteric vein thrombosis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Pancreatitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Proctitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Rectal ulcer	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Subileus	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
General disorders
Asthenia	2/256 (0.8%)		0/247 (0%)		2/503 (0.4%)
Non-cardiac chest pain	1/256 (0.4%)		1/247 (0.4%)		2/503 (0.4%)
Oedema peripheral	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Pyrexia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Hepatobiliary disorders
Chronic hepatic failure	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Immune system disorders
Drug hypersensitivity	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Infections and infestations
Anal abscess	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Appendicitis	1/256 (0.4%)		1/247 (0.4%)		2/503 (0.4%)
Bronchopneumonia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cellulitis	3/256 (1.2%)		0/247 (0%)		3/503 (0.6%)
Cerebral toxoplasmosis	1/256 (0.4%)		1/247 (0.4%)		2/503 (0.4%)
Clostridium difficile colitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cryptococcosis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cytomegalovirus chorioretinitis	1/256 (0.4%)		1/247 (0.4%)		2/503 (0.4%)
Cytomegalovirus colitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cytomegalovirus infection	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Cytomegalovirus myelomeningoradiculitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Gastroenteritis	2/256 (0.8%)		2/247 (0.8%)		4/503 (0.8%)
HIV infection	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Hepatitis c	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Herpes simplex	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Herpes zoster	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Histoplasmosis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Histoplasmosis disseminated	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Keratitis fungal	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Localised infection	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Meningitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Mycobacterium avium complex infection	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Oesophageal candidiasis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Oral candidiasis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Papilloma viral infection	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Pneumocystis jiroveci pneumonia	3/256 (1.2%)		0/247 (0%)		3/503 (0.6%)
Pneumonia	5/256 (2%)		4/247 (1.6%)		9/503 (1.8%)
Pneumonia influenzal	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Postoperative wound infection	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Pyomyositis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Pyothorax	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Scrotal abscess	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Sepsis	2/256 (0.8%)		2/247 (0.8%)		4/503 (0.8%)
Staphylococcal bacteraemia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Staphylococcal sepsis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Strongyloidiasis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Tuberculosis of central nervous system	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Urinary tract infection	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Urinary tract infection fungal	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Injury, poisoning and procedural complications
Subdural haematoma	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Wrist fracture	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Investigations
Arteriogram coronary	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Blood amylase increased	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Blood creatinine increased	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Haemoglobin decreased	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Lipase increased	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Weight decreased	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Metabolism and nutrition disorders
Dehydration	2/256 (0.8%)		1/247 (0.4%)		3/503 (0.6%)
Gout	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Hypertriglyceridaemia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Hypokalaemia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Hyponatraemia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Back pain	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Muscular weakness	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Osteoarthritis	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Osteonecrosis	1/256 (0.4%)		2/247 (0.8%)		3/503 (0.6%)
Osteoporosis	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Pain in extremity	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Pathological fracture	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Female reproductive tract carcinoma in situ	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Haemangioma of liver	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Hodgkin's disease	0/256 (0%)		2/247 (0.8%)		2/503 (0.4%)
Lymphoma	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Squamous cell carcinoma	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Uterine leiomyoma	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Nervous system disorders
Cerebrovascular accident	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Coma	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Dementia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Hypoaesthesia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Lacunar infarction	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Post herpetic neuralgia	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Transient ischaemic attack	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Psychiatric disorders
Confusional state	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Depression	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Generalised anxiety disorder	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Major depression	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Mood disorder due to a general medical condition	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Psychotic disorder	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Renal and urinary disorders
Renal failure	2/256 (0.8%)		0/247 (0%)		2/503 (0.4%)
Renal failure acute	1/256 (0.4%)		2/247 (0.8%)		3/503 (0.6%)
Renal impairment	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Reproductive system and breast disorders
Cervical dysplasia	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Skin and subcutaneous tissue disorders
Night sweats	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Rash macular	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Surgical and medical procedures
Abdominal hernia repair	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Abdominoplasty	0/256 (0%)		1/247 (0.4%)		1/503 (0.2%)
Breast cosmetic surgery	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Liposuction	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Vascular disorders
Hypertension	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Phlebitis	1/256 (0.4%)		0/247 (0%)		1/503 (0.2%)
Other (Not Including Serious) Adverse Events
	DUET PLACEBO		DUET TMC125		All Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	160/256 (62.5%)		137/247 (55.5%)		297/503 (59%)
Gastrointestinal disorders
Diarrhoea	32/256 (12.5%)		24/247 (9.7%)		56/503 (11.1%)
Nausea	20/256 (7.8%)		15/247 (6.1%)		35/503 (7%)
General disorders
Injection site nodule	14/256 (5.5%)		8/247 (3.2%)		22/503 (4.4%)
Pyrexia	13/256 (5.1%)		6/247 (2.4%)		19/503 (3.8%)
Infections and infestations
Bronchitis	18/256 (7%)		12/247 (4.9%)		30/503 (6%)
Herpes simplex	32/256 (12.5%)		17/247 (6.9%)		49/503 (9.7%)
Influenza	18/256 (7%)		18/247 (7.3%)		36/503 (7.2%)
Nasopharyngitis	21/256 (8.2%)		15/247 (6.1%)		36/503 (7.2%)
Oral candidiasis	23/256 (9%)		14/247 (5.7%)		37/503 (7.4%)
Sinusitis	19/256 (7.4%)		23/247 (9.3%)		42/503 (8.3%)
Upper respiratory tract infection	14/256 (5.5%)		11/247 (4.5%)		25/503 (5%)
Urinary tract infection	14/256 (5.5%)		8/247 (3.2%)		22/503 (4.4%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	12/256 (4.7%)		15/247 (6.1%)		27/503 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/256 (2.7%)		14/247 (5.7%)		21/503 (4.2%)
Nervous system disorders
Headache	18/256 (7%)		10/247 (4%)		28/503 (5.6%)
Psychiatric disorders
Insomnia	13/256 (5.1%)		7/247 (2.8%)		20/503 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	12/256 (4.7%)		14/247 (5.7%)		26/503 (5.2%)
Skin and subcutaneous tissue disorders
Rash	24/256 (9.4%)		4/247 (1.6%)		28/503 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator agrees that before he/she publishes any results of this trial, he/she shall provide the sponsor with at least 45 days for full review of the pre-publication manuscript prior to submission of the manuscript to the publisher.