Trial Outcomes & Findings for A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients (NCT NCT01199939)

Results Overview

CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Week 48

Results posted on

2013-12-04

Participant Flow

The study was conducted between 29 March 2010 and 5 October 2012 and recruited patients from US (17 sites) and Puerto Rico (1 site).

54 participants were treated with Etravirine and Darunavir/ritonavir in this study.

Participant milestones

Participant milestones
Measure	ETR + DRV/Rtv Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Overall Study STARTED	54
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	ETR + DRV/Rtv Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Overall Study Adverse Event	4
Overall Study Protocol Violation	3
Overall Study Lost to Follow-up	2
Overall Study Reached a virologic endpoint	4

Baseline Characteristics

A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ETR + DRV/Rtv n=54 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Age Continuous	44.4 years STANDARD_DEVIATION 12.82 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Region of Enrollment Puerto Rico	4 participants n=5 Participants
Region of Enrollment USA	50 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Intent-To-Treat Non-Virologic failure (VF) censored: Participants who took at least one dose of any of the study medications and did not withdraw for reasons other than VF or experienced VF prior to discontinuation. Participants with evaluable data at Week 48

CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=45 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Number of Participants With Confirmed Virologic Response (CVR) at Week 48	40 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 4

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 4

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=52 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4	-1.77 log10 Copies/mL Interval -3.2 to 3.1

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 8

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=50 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8	-2.04 log10 Copies/mL Interval -3.3 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 12

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=45 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12	-2.18 log10 Copies/mL Interval -3.6 to -0.1

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 16

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 16

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=45 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16	-2.29 log10 Copies/mL Interval -4.0 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 20

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 20

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=44 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20	-2.27 log10 Copies/mL Interval -4.0 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 24

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=45 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24	-2.17 log10 Copies/mL Interval -3.9 to -0.2

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 30

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 30

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=43 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30	-2.28 log10 Copies/mL Interval -4.0 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 36

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 36

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=42 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36	-2.24 log10 Copies/mL Interval -3.9 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 42

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 42

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=41 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42	-2.29 log10 Copies/mL Interval -3.9 to -0.5

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: Intent-to-treat participants who received at least one dose of any of the study medication with evaluable data at Week 48

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=39 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48	-2.29 log10 Copies/mL Interval -3.9 to 2.4

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 48

Population: Intent-To-Treat participants enrolled in the study who took at least one dose of any of the study medications

CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=54 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Time to Reach First Confirmed Virologic Response	82.98 Days Standard Error 6.684

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 48

Population: Intent-To-Treat participants enrolled in the study who took at least one dose of any of the study medications

Virologic Failure is defined as participant who is a rebounder or a non-responder. Rebounder participant is defined as a participant who is still in the study at Week 12 and first achieves 2 consecutive virologic responses (\<50 copies/mL) followed by 2 consecutive non-responses or a discontinued participant (any reason) for which the last observed time point shows a non-response. Non responder participant is defined as a participant who is still in the study at Week 12 and never achieves 2 consecutive responses.

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=54 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Number of Participants With Virologic Failure	7 Participants 6.684

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: Intent-To-Treat participants enrolled in the study who took at least one dose of any of the study medications

Outcome measures

Outcome measures
Measure	ETR + DRV/Rtv n=54 Participants Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48 CD4	168 cells/uL Standard Deviation 153.3
Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48 CD8	-69 cells/uL Standard Deviation 289.4

Adverse Events

ETR + DRV/Rtv

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ETR + DRV/Rtv n=54 participants at risk Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
General disorders Fatigue	1.9% 1/54 • 48 weeks
General disorders Pyrexia	1.9% 1/54 • 48 weeks
Infections and infestations Abscess Jaw	1.9% 1/54 • 48 weeks
Infections and infestations Pneumonia	1.9% 1/54 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's Disease	1.9% 1/54 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/54 • 48 weeks

Other adverse events

Other adverse events
Measure	ETR + DRV/Rtv n=54 participants at risk Etravirine (ETR) 400mg + Darunavir (DRV) 800mg/Ritonavir (rtv) 100mg once daily orally for 48 weeks
Gastrointestinal disorders Abdominal Pain	5.6% 3/54 • 48 weeks
Gastrointestinal disorders Diarrhoea	14.8% 8/54 • 48 weeks
Gastrointestinal disorders Nausea	5.6% 3/54 • 48 weeks
General disorders Fatigue	5.6% 3/54 • 48 weeks
Infections and infestations Sinusitis	5.6% 3/54 • 48 weeks
Infections and infestations Upper Respiratory Tract Infection	11.1% 6/54 • 48 weeks
Investigations Fibrin D Dimer Increased	5.6% 3/54 • 48 weeks
Investigations Low Density Lipoprotein Increased	7.4% 4/54 • 48 weeks
Respiratory, thoracic and mediastinal disorders Cough	5.6% 3/54 • 48 weeks
Respiratory, thoracic and mediastinal disorders Nasal Congestion	7.4% 4/54 • 48 weeks
Skin and subcutaneous tissue disorders Rash	11.1% 6/54 • 48 weeks

Additional Information

SENIOR MEDICAL DIRECTOR

Janssen Pharmaceuticals

Phone: 1 609 730-2931

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60