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:

Collaborator:

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Information provided by:

Tibotec, Inc

ClinicalTrials.gov Identifier:

NCT00534352

First received: September 21, 2007

Last updated: October 18, 2010

Last verified: October 2010

History of Changes

Results First Received: May 6, 2009

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	HIV-1 Infection
Intervention:	Drug: TMC125; darunavir; ritonavir

Participant Flow

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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
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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.

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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Outcome Measures

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1. Primary:

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

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2. Secondary:

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

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3. Secondary:

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

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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 ]

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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 ]

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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 ]

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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 ]

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8. Secondary:

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

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9. Secondary:

Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) [ Time Frame: Day 8, 14, 22, 28, 42 and Week 48 ]

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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 ]

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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 ]

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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 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

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
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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

No publications provided by Tibotec, Inc

Publications automatically indexed to this study:

DeJesus E, Lalezari JP, Osiyemi OO, Ruane PJ, Ryan R, Kakuda TN, Witek J. Pharmacokinetics of once-daily etravirine without and with once-daily darunavir/ritonavir in antiretroviral-naive HIV type-1-infected adults. Antivir Ther. 2010;15(5):711-20.

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
Study First Received:	September 21, 2007
Results First Received:	May 6, 2009
Last Updated:	October 18, 2010
Health Authority:	United States: Food and Drug Administration

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