Enfuvirtide/Current Protease Inhibitor Switch to PREZISTA (Darunavir)/Ritonavir + TMC125 in HIV Patients With Enfuvirtide Side Effects.

• ClinicalTrials.gov Identifier: NCT00460746
• Recruitment Status: Completed
• First Posted: April 16, 2007
• Results First Posted: November 10, 2009
• Last Update Posted: July 31, 2013
• Sponsor: Tibotec, Inc
• Collaborator: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Information provided by (Responsible Party): Tibotec, Inc

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV
• Intervention: Drug: TMC125, Darunavir; Ritonavir
• Enrollment: 10

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Period Title: Overall Study
Started	10
Completed	8
Not Completed	2
Reason Not Completed
Adverse Event	1
Lost to Follow-up	1

Baseline Characteristics

Arm/Group Title		Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description		Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Baseline Participants		10
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	10 participants
		48; (35 to 61)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Female	0 0.0%
	Male	10 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	10 participants
White		6
Hispanic		4
Viral Load <50 copies/mL; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	10 participants
		10
CD4 count; Median (Full Range); Unit of measure: Cells/mm^3
	Number Analyzed	10 participants
		301; (187 to 663)

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Maintain Plasma HIV Viral Load Measurements < 400 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Description	[Not Specified]
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

ITT population. One subject (001) who discontinued due to adverse events had a VL < 50 copies/mL at Week 4. Another subject (013) who was lost to follow-up had VL <50 copies/mL through Week 36.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Measure Type: Number; Unit of Measure: percentage of participants
Baseline (Day 1)	100
Week 2	100
Week 4	100
Week 8	90
Week 12	80
Week 16	90
Week 24	90
Week 36	90
Week 48	80
Post-Treatment Follow Up	90

2. Secondary Outcome

Title	Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure.
Description	[Not Specified]
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

ITT population. One subject (001) who discontinued due to adverse events had a VL < 50 copies/mL at Week 4. Another subject (013) who was lost to follow-up had VL <50 copies/mL through Week 36.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Measure Type: Number; Unit of Measure: percentage of participants
Baseline (Day 1)	100
Week 2	90
Week 4	90
Week 8	90
Week 12	80
Week 16	90
Week 24	90
Week 36	90
Week 48	80
Post-Treatment Follow Up	90

3. Secondary Outcome

Title	CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent To Treat (ITT), last observation carried forward (LOCF).

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: cells/mm^3
Baseline (Day 1)	301.0; (187.0 to 663.0)
Week 4 Change from Baseline	-12.0; (-32.0 to 61.0)
Week 8 Change from Baseline	-32.0; (-169.0 to 81.0)
Week 12 Change from Baseline	-17.0; (-100.0 to 61.0)
Week 16 Change from Baseline	-7.0; (-73.0 to 81.0)
Week 24 Change from Baseline	19.0; (-36.0 to 71.0)
Week 36 Change from Baseline	38.0; (-59.0 to 117.0)
Week 48 Change from Baseline	63.5; (-53.0 to 100.0)

4. Secondary Outcome

Title	CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: cells/mm^3
Baseline (Day 1)	338.3 (135.91)
Week 4 Change from Baseline	2.3 (31.22)
Week 8 Change from Baseline	-25.0 (72.04)
Week 12 Change from Baseline	-18.9 (44.25)
Week 16 Change from Baseline	0.5 (53.58)
Week 24 Change from Baseline	24.5 (34.00)
Week 36 Change from Baseline	22.7 (58.84)
Week 48 Change from Baseline	47.3 (48.03)

5. Secondary Outcome

Title	Median Change From Baseline in Triglycerides at Week 48.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mg/dL
Baseline (Day 1)	229.0; (121.0 to 402.0)
Week 48 Change from Baseline	-24.5; (-227.0 to 78.0)

6. Secondary Outcome

Title	Median Change From Baseline in Total Cholesterol at Week 48.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mg/dL
Baseline (Day 1)	189.0; (159.0 to 244.0)
Week 48 Change from Baseline	-27.5; (-44.0 to 27.0)

7. Secondary Outcome

Title	Median Change From Baseline in LDL Cholesterol at Week 48.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mg/dL
Baseline (Day 1)	100.0; (63.0 to 149.0)
Week 48 Change from Baseline	-9.0; (-30.0 to 17.0)

8. Secondary Outcome

Title	Median Change From Baseline in HDL Cholesterol.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mg/dL
Baseline (Day 1)	47.5; (25.0 to 54.0)
Week 48 Change from Baseline	-2.5; (-15.0 to 10.0)

9. Secondary Outcome

Title	Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: ratio of TC and HDL
Baseline (Day 1)	4.7; (2.94 to 6.40)
Week 48 Change from Baseline	-0.3; (-0.82 to 1.20)

10. Secondary Outcome

Title	Median Change From Baseline in Glucose at Week 48.
Description	[Not Specified]
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT , LOCF.

Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description:	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
Overall Number of Participants Analyzed	10
Median (Full Range); Unit of Measure: mg/dL
Baseline (Day 1)	92.5; (74.0 to 105.0)
Week 48 Change from Baseline	1.0; (-21.0 to 12.0)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Darunavir(TMC114)/Eravirine(TMC125)
Arm/Group Description	Darunavir/ritonavir (DRV/r) combined with Etravirine ([ETR] also known as TMC125) when current protease inhibitor(s) (PIs), non-nucleoside reverse transriptase inhibitor(s) (NNRTIs), and enfuviritide (ENF) were replaced by DRV/r and ETR in subjects with intolerance to ENF.
All-Cause Mortality
	Darunavir(TMC114)/Eravirine(TMC125)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Darunavir(TMC114)/Eravirine(TMC125)
	Affected / at Risk (%)	# Events
Total	1/10 (10.00%)
Hepatobiliary disorders
Cholecystitis acute * 1 [1]	1/10 (10.00%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (10.0); [1] Noted by investigator as doubtfully related to study drug
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Darunavir(TMC114)/Eravirine(TMC125)
	Affected / at Risk (%)	# Events
Total	10/10 (100.00%)
Gastrointestinal disorders
Constipation * 1 [1]	1/10 (10.00%)	1
Diarrhea * 2 [1]	3/10 (30.00%)	3
Dry mouth * 3 [1]	1/10 (10.00%)	1
Nausea * 1 [1]	1/10 (10.00%)	1
General disorders
Abdominal pain upper * 1 [1]	1/10 (10.00%)	1
Fatigue * 2 [1]	4/10 (40.00%)	4
Pain * 1 [1]	1/10 (10.00%)	1
Infections and infestations
Diverticulitis * 1 [1]	1/10 (10.00%)	1
Metabolism and nutrition disorders
Decreased appetite * 1 [1]	1/10 (10.00%)	1
Hypercholesterolaemia * 1 [1]	1/10 (10.00%)	1
Nervous system disorders
Amnesia * 1 [1]	1/10 (10.00%)	1
Disturbance in attention * 1 [1]	1/10 (10.00%)	1
Dizziness * 1 [1]	1/10 (10.00%)	1
Headache * 2 [1]	3/10 (30.00%)	3
Somnolence * 1 [1]	1/10 (10.00%)	1
Psychiatric disorders
Depression * 2 [1]	2/10 (20.00%)	2
Insomnia * 2 [1]	2/10 (20.00%)	2
Skin and subcutaneous tissue disorders
Dermatitis * 1 [1]	1/10 (10.00%)	1
Rash * 2 [1]	3/10 (30.00%)	3
Vascular disorders
Heart rate increase * 1 [1]	1/10 (10.00%)	1
Hypertension * 2 [1]	2/10 (20.00%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (10.0); 2 Term from vocabulary, MedDRA 10.0; 3 Term from vocabulary, MesDRA 10.0; [1] Relationship is other than not related.

Limitations and Caveats

Conclusions on efficacy and safety are limited as the target enrollment of 40 subjects was not reached due to a shortage of eligible subjects.

More Information

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.

If TTCA does not publish within 12 months after study conclusion or after TTCA confirms there will be no multicenter publication, Institution may publish their results from their site individually, provided TTCA has 60 day review for confidentiality and additional 60 day delay for patent application.

Results Point of Contact

• Name/Title: Vice President, Tibotec Therapeutics Clinical Affairs
• Organization: Tibotec Therapeutics Clinical Affairs, Division of Centocor Ortho Biotech Services, LLC
• Phone: 877-732-2488
• EMail: rfalcon@its.jnj.com

• Responsible Party: Tibotec, Inc
• ClinicalTrials.gov Identifier: NCT00460746
• Other Study ID Numbers: CR011866; TMC114HIV3009 ( Other Identifier: Tibotec, Inc. )
• First Submitted: April 13, 2007
• First Posted: April 16, 2007
• Results First Submitted: October 2, 2009
• Results First Posted: November 10, 2009
• Last Update Posted: July 31, 2013