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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).

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00534352
First Posted: September 24, 2007
Last Update Posted: April 16, 2015
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.
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:
Tibotec, Inc
Results First Submitted: May 6, 2009  
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

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
TDF/FTC +/- TMC125 +/- DRV/Rtv

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.

Participant Flow for 4 periods

 Period 1:   Treatment A: TMC125 + TDF/FTC
    TDF/FTC +/- TMC125 +/- DRV/Rtv
STARTED   23 
COMPLETED   21 
NOT COMPLETED   2 
Physician Decision                1 
Lost to Follow-up                1 

Period 2:   Treatment B: TMC125 + TDF/FTC + DRV/Rtv
    TDF/FTC +/- TMC125 +/- DRV/Rtv
STARTED   21 
COMPLETED   21 
NOT COMPLETED   0 

Period 3:   Treatment C: DRV/Rtv + TDF/FTC
    TDF/FTC +/- TMC125 +/- DRV/Rtv
STARTED   21 
COMPLETED   20 
NOT COMPLETED   1 
Physician Decision                1 

Period 4:   Optional Extension: DRV/Rtv + TDF/FTC
    TDF/FTC +/- TMC125 +/- DRV/Rtv
STARTED   18 
COMPLETED   14 
NOT COMPLETED   4 
Physician Decision                1 
Lost to Follow-up                2 
Pregnancy                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
TDF/FTC +/- TMC125 +/- DRV/Rtv

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.

Baseline Measures
   TDF/FTC +/- TMC125 +/- DRV/Rtv 
Overall Participants Analyzed 
[Units: Participants]
 		 23 
Age 
[Units: Participants]
 		 
<=18 years   0 
Between 18 and 65 years   22 
>=65 years   1 
Age 
[Units: Years]
Mean (Standard Deviation) 		 35.87  (13.264) 
Gender 
[Units: Participants]
 		 
Female   3 
Male   20 
Race/Ethnicity, Customized 
[Units: Participants]
 		 
Black   9 
Caucasian / White   9 
Hispanic   5 
Region of Enrollment 
[Units: Participants]
 		 
United States   23 
CYP2C19 Genotyping [1] 
[Units: 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] There are 21 participants with genotyping data.
CYP2C9 Genotyping [1] 
[Units: Participants]
 		 
CYP2C9*1/CYP2C1*1 : Normal Phenotype   19 
CYP2C9*1/CYP2C1*3 : Intermediate Phenotype   2 
No data   2 
[1] There are 21 participants with genotyping data.
Family History Related to Skin Disease 
[Units: Participants]
 		 
No   18 
Yes   5 
Body Mass Index 
[Units: Kg/m2]
Mean (Standard Deviation) 		 26.33  (4.629) 
Height 
[Units: Cm]
Mean (Standard Deviation) 		 172.73  (8.405) 
Weight 
[Units: Kg]
Mean (Standard Deviation) 		 78.58  (13.711) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av   [ Time Frame: 6 weeks ]
  Show Outcome Measure 1

2.  Secondary:   Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 2

3.  Secondary:   Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 3

4.  Secondary:   Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 4

5.  Secondary:   Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 5

6.  Secondary:   Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL)   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 6

7.  Secondary:   Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct   [ Time Frame: Day 1 through 42 and Week 48 ]
  Show Outcome Measure 7

8.  Secondary:   Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides   [ Time Frame: Day 1 through 48 and Week 48 ]
  Show Outcome Measure 8

9.  Secondary:   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 9

10.  Secondary:   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 10

11.  Secondary:   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 11

12.  Secondary:   CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case)   [ Time Frame: Baseline, Day 8, 14, 22, 28 & 42 and Week 48 ]
  Show Outcome Measure 12


  Serious Adverse Events
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Time Frame Baseline, Day 8, 14, 22, 28, 42 and Week 48
Additional Description No text entered.

Reporting Groups
  Description
Treatment A TMC125 + TDF/FTC
Treatment B TMC125 + TDF/FTC + DRV/rtv
Treatment C DRV/rtv + TDF/FTC
Optional Extension DRV/rtv + TDF/FTC

Serious Adverse Events
    Treatment A   Treatment B   Treatment C   Optional Extension
Total, Serious Adverse Events         
# participants affected / at risk   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         
# participants affected / at risk   0/23 (0.00%)   0/21 (0.00%)   0/21 (0.00%)   1/18 (5.56%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (11.0)




  Other Adverse Events
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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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