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

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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:
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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
Hide 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)
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.
Hide Description [Not Specified]
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Hide Description [Not Specified]
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent To Treat (ITT), last observation carried forward (LOCF).
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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.
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT , LOCF.
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Darunavir(TMC114)/Eravirine(TMC125)
Hide 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   --/--    
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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.
Conclusions on efficacy and safety are limited as the target enrollment of 40 subjects was not reached due to a shortage of eligible subjects.
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
Responsible Party: Tibotec, Inc
ClinicalTrials.gov Identifier: NCT00460746     History of Changes
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