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Trial record 34 of 35 for:    " August 29, 2007":" September 28, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

A Study to Evaluate the Pharmacokinetic Profile (How the Body Absorbs, Distributes, Metabolizes and Eliminates a Drug) of TMC125 Plus Tenofovir/Emtricitabine Once Daily With or Without Darunavir/r Once Daily in Antiretroviral (ARV) Naive HIV-1 Patients (Patients Have Never Received ARV Treatment).

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00534352
Recruitment Status : Completed
First Posted : September 24, 2007
Results First Posted : April 12, 2010
Last Update Posted : April 16, 2015
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:
Tibotec, Inc

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Intervention Drug: TMC125; darunavir; ritonavir
Enrollment 23
Recruitment Details The 42-day open-label main treatment phase of this trial was conducted from 10 December 2007 to 27 May 2008. Four investigators from the US participated in this multicenter trial. A total of 35 subjects were screened and of these, 23 subjects entered the trial and started the first treatment phase
Pre-assignment Details  
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Period Title: Treatment A: TMC125 + TDF/FTC
Started 23
Completed 21
Not Completed 2
Reason Not Completed
Physician Decision             1
Lost to Follow-up             1
Period Title: Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Started 21
Completed 21
Not Completed 0
Period Title: Treatment C: DRV/Rtv + TDF/FTC
Started 21
Completed 20
Not Completed 1
Reason Not Completed
Physician Decision             1
Period Title: Optional Extension: DRV/Rtv + TDF/FTC
Started 18
Completed 14
Not Completed 4
Reason Not Completed
Physician Decision             1
Lost to Follow-up             2
Pregnancy             1
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
<=18 years
0
   0.0%
Between 18 and 65 years
22
  95.7%
>=65 years
1
   4.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants
35.87  (13.264)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
3
  13.0%
Male
20
  87.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants
Black 9
Caucasian / White 9
Hispanic 5
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 23 participants
23
CYP2C19 Genotyping   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants
CYP2C19*1/CYP2C19*1 : Normal Phenotype 5
CYP2C19*1/CYP2C19*17 : Rapid Phenotype 5
CYP2C19*1/CYP2C19*2 : Intermediate Phenotype 7
CYP2C19*17/CYP2C19*17 : Ultrarapid Phenotype 1
CYP2C19*17/CYP2C19*2 : Normal Phenotype 2
CYP2C19*2/CYP2C19*2 : Poor Phenotype 1
No data 2
[1]
Measure Description: There are 21 participants with genotyping data.
CYP2C9 Genotyping   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants
CYP2C9*1/CYP2C1*1 : Normal Phenotype 19
CYP2C9*1/CYP2C1*3 : Intermediate Phenotype 2
No data 2
[1]
Measure Description: There are 21 participants with genotyping data.
Family History Related to Skin Disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants
No 18
Yes 5
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 23 participants
26.33  (4.629)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 23 participants
172.73  (8.405)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 23 participants
78.58  (13.711)
1.Primary Outcome
Title Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av
Hide Description At visit Days 14 & 28, samples were collected pre-dose and at 1, 2, 3, 4, 6, 9, and 12 hours post-dose. An additional sample was taken at 24 hours (Day 15 or 29 as applicable) post-dose.
Time Frame 6 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention To Treat (ITT) population
Arm/Group Title Treatment A: TMC125 + TDF/FTC Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Hide Arm/Group Description:
Treatment A: TMC125 + TDF/FTC.
Treatment B: TMC125 + TDF/FTC + DRV/rtv.
Overall Number of Participants Analyzed 23 21
Measure Type: Number
Unit of Measure: participants
23 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Comments Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence was shown for Cmin as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No p-values.
Method Mixed Models Analysis (Cmin)
Comments The linear mixed effects model was controlled for treatment as fixed effects, and subject as a random effect.
Method of Estimation Estimation Parameter Least Square (LS) mean ratio
Estimated Value 95.47
Confidence Interval 90%
82.77 to 110.1
Estimation Comments The results are for the mean ratio of Cmin. Numerator: Treatment B Denominator: Treatment A
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Comments Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence was shown for Cmax as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No p-values.
Method Mixed Models Analysis (Cmax)
Comments The linear mixed effects model was controlled for treatment as fixed effects, and subject as a random effect.
Method of Estimation Estimation Parameter Least Square (LS) mean ratio
Estimated Value 102.6
Confidence Interval 90%
92.91 to 113.3
Estimation Comments The results are for the mean ratio of Cmax. Numerator: Treatment B Denominator: Treatment A
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Comments Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence was shown for AUC24 as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No p-values.
Method Mixed Models Analysis (AUC24)
Comments The linear mixed effects model was controlled for treatment as fixed effects, and subject as a random effect.
Method of Estimation Estimation Parameter LS means of ratios
Estimated Value 98.97
Confidence Interval 90%
89.23 to 109.8
Estimation Comments The results are for the mean ratio of AUC24. Numerator: Treatment B Denominator: Treatment A
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv
Comments Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence was shown for Css,av as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No p-values.
Method Mixed Models Analysis (Css,av)
Comments The linear mixed effects model was controlled for treatment as fixed effects, and subject as a random effect.
Method of Estimation Estimation Parameter Least Square (LS) mean ratio
Estimated Value 99.30
Confidence Interval 90%
89.39 to 110.3
Estimation Comments The results are for the mean ratio of Css,av. Numerator: Treatment B Denominator: Treatment A
2.Secondary Outcome
Title Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia
Hide Description

Number of Participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia.

Worst Grade is based on the National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity grading scale, 0,1,2,3,4 and 5 : None, Mild, Moderate, Severe, Life-threatening and Death.

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 21 21 20 18
Measure Type: Number
Unit of Measure: participants
Grade 1 1 2 0 2
Grade 2 1 0 1 1
3.Secondary Outcome
Title Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia
Hide Description

Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia.

Worst Grade is based on the DAIDS toxicity grading scale 0-5: No Toxicity-Death.

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 21 21 20 18
Measure Type: Number
Unit of Measure: participants
Grade 1 0 2 0 1
Grade 2 0 1 0 0
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin
Hide Description

Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin.

Normal Range: 3.0 - 27.0 ulU/mL

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 21 21 19 16
Measure Type: Number
Unit of Measure: participant
Below 3.0 ulU/mL 1 2 1 1
Above 27.0 ulU/mL 1 3 2 3
5.Secondary Outcome
Title Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral
Hide Description

Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral.

Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 21 20 20 7
Measure Type: Number
Unit of Measure: participants
Grade 1 0 0 2 1
Grade 2 0 0 0 0
6.Secondary Outcome
Title Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL)
Hide Description

Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density lipoprotein (HDL).

Normal Range:

40 - 59 mG/dL 1.03 - 1.53 mmol/L

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 14 15 15 7
Measure Type: Number
Unit of Measure: participants
Below 40 mG/dL (1.03 mmol/L) 4 8 6 2
Above 59 mG/dL (1.53 mmol/L) 0 0 0 1
7.Secondary Outcome
Title Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct
Hide Description

Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density lipoprotein (LDL) Direct.

Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.

Time Frame Day 1 through 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 21 20 20 7
Measure Type: Number
Unit of Measure: participants
Grade 1 0 0 1 1
Grade 2 0 0 1 1
8.Secondary Outcome
Title Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides
Hide Description

Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides.

Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.

Time Frame Day 1 through 48 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description:
TMC125 + TDF/FTC
TMC125 + TDF/FTC + DRV/rtv
DRV/rtv + TDF/FTC
DRV/rtv + TDF/FTC
Overall Number of Participants Analyzed 20 19 20 7
Measure Type: Number
Unit of Measure: participants
Grade 1 0 0 0 0
Grade 2 0 0 0 0
9.Secondary Outcome
Title Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case)
Hide Description Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case).
Time Frame Day 8, 14, 22, 28, 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description:

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: participants
Day 8 (n=19) 0
Day 14 (n=21) 3
Day 22 (n=19) 4
Day 28 (n=20) 6
Day 42 (n=20) 7
Week 48 (n=13) 10
10.Secondary Outcome
Title Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case)
Hide Description Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case).
Time Frame Baseline, Day 8, 14, 22, 28 & 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT (Observed)
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description:

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Overall Number of Participants Analyzed 23
Mean (Standard Error)
Unit of Measure: copies/mL
Baseline (n=23) 4.19  (0.157)
Day 8 (n=19) -1.41  (0.094)
Day 14 (n=21) -1.71  (0.090)
Day 22 (n=19) -1.77  (0.094)
Day 28 (n=20) -1.86  (0.123)
Day 42 (n=20) -2.04  (0.127)
Week 48 (n=13) -2.30  (0.237)
11.Secondary Outcome
Title CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case)
Hide Description CD4+ Cell Count (x 10^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case).
Time Frame Baseline, Day 8, 14, 22, 28 & 42 ans Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description:

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Overall Number of Participants Analyzed 23
Median (Full Range)
Unit of Measure: x 10^6 cell/L
Baseline (n=23)
403.0
(144.0 to 895.0)
Day 8 (n=20)
45.5
(-126.0 to 209.0)
Day 14 (n=20)
94.0
(-78.0 to 426.0)
Day 22 (n=20)
59.0
(-184.0 to 251.0)
Day 28 (n=21)
62.0
(-170.0 to 329.0)
Day 42 (n=19)
56.0
(-221.0 to 472.0)
Week 48 (n=14)
160.0
(-124.0 to 411.0)
12.Secondary Outcome
Title CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case)
Hide Description [Not Specified]
Time Frame Baseline, Day 8, 14, 22, 28 & 42 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT (Observed)
Arm/Group Title TDF/FTC +/- TMC125 +/- DRV/Rtv
Hide Arm/Group Description:

In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.

In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.

In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.

Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC.

Overall Number of Participants Analyzed 23
Median (Full Range)
Unit of Measure: Percent Change from Baseline
Baseline (n=23)
26.2
(11.4 to 48.3)
Day 8 (n=20)
0.1
(-7.7 to 8.1)
Day 14 (n=20)
4.2
(-3.5 to 10.5)
Day 22 (n=20)
1.8
(-4.5 to 7.9)
Day 28 (n=21)
3.0
(-0.9 to 11.2)
Day 42 (n=19)
4.2
(-2.7 to 14.4)
Week 48 (n=14)
3.8
(-0.2 to 11.5)
Time Frame Baseline, Day 8, 14, 22, 28, 42 and Week 48
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B Treatment C Optional Extension
Hide Arm/Group Description TMC125 + TDF/FTC TMC125 + TDF/FTC + DRV/rtv DRV/rtv + TDF/FTC DRV/rtv + TDF/FTC
All-Cause Mortality
Treatment A Treatment B Treatment C Optional Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment A Treatment B Treatment C Optional Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/23 (0.00%)   0/21 (0.00%)   0/21 (0.00%)   1/18 (5.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Burkitt's Lymphoma * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment A Treatment B Treatment C Optional Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/23 (43.48%)   9/21 (42.86%)   4/21 (19.05%)   13/18 (72.22%) 
Cardiac disorders         
Sinus Tachycardia * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Eye disorders         
Conjunctival Haemorrhage * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Conjunctivitis * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Gastrointestinal disorders         
Anogenital Dysplasia * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Constipation * 1  1/23 (4.35%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Diarrhoea * 1  1/23 (4.35%)  2/21 (9.52%)  1/21 (4.76%)  3/18 (16.67%) 
Dyspepsia * 1  0/23 (0.00%)  0/21 (0.00%)  1/21 (4.76%)  1/18 (5.56%) 
Gastrooesophageal Reflux Disease * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Haemorrhoids * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Nausea * 1  2/23 (8.70%)  4/21 (19.05%)  0/21 (0.00%)  2/18 (11.11%) 
Oral Pain * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Toothache * 1  0/23 (0.00%)  0/21 (0.00%)  1/21 (4.76%)  2/18 (11.11%) 
General disorders         
Fatigue * 1  1/23 (4.35%)  2/21 (9.52%)  0/21 (0.00%)  0/18 (0.00%) 
Infections and infestations         
Bronchitis * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Folliculitis * 1  1/23 (4.35%)  1/21 (4.76%)  0/21 (0.00%)  1/18 (5.56%) 
Syphilis * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Upper Respiratory Tract Infection * 1  0/23 (0.00%)  1/21 (4.76%)  1/21 (4.76%)  1/18 (5.56%) 
Urinary Tract Infection * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Injury, poisoning and procedural complications         
Drug Exposure During Pregnancy * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Investigations         
Blood Urine Present * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Nervous system disorders         
Areflexia * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Dizziness * 1  1/23 (4.35%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Headache * 1  2/23 (8.70%)  1/21 (4.76%)  0/21 (0.00%)  1/18 (5.56%) 
Intracranial Hypotension * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Psychiatric disorders         
Anxiety * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Insomnia * 1  0/23 (0.00%)  1/21 (4.76%)  0/21 (0.00%)  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders         
Bronchitis Chronic * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Cough * 1  1/23 (4.35%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Sinus Congestion * 1  0/23 (0.00%)  1/21 (4.76%)  0/21 (0.00%)  1/18 (5.56%) 
Skin and subcutaneous tissue disorders         
Acne Cystic * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Alopecia * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
Dermatitus * 1  0/23 (0.00%)  0/21 (0.00%)  0/21 (0.00%)  2/18 (11.11%) 
Pruritus * 1  2/23 (8.70%)  0/21 (0.00%)  0/21 (0.00%)  1/18 (5.56%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
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: Vice President Clinical Affairs, Tibotec Therapeutics Clinical Affairs, a Division of Ortho Biotech Clinical Affairs, LLC
ClinicalTrials.gov Identifier: NCT00534352     History of Changes
Other Study ID Numbers: CR014485
TMC125HIV2032
First Submitted: September 21, 2007
First Posted: September 24, 2007
Results First Submitted: May 6, 2009
Results First Posted: April 12, 2010
Last Update Posted: April 16, 2015