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
  Purpose

The purpose of this study is to determine the pharmacokinetic profile of TMC125 400mg with tenofovir DF/emtricitabine FDC (fixed dose combination) 300/200mg all dosed once daily with and without darunavir/ritonavir 800/100 mg once daily in HIV-1 infected, antiretroviral (ARV) naÃ-ve patients (patients who have never received ARV treatment).


Condition Intervention Phase
HIV-1 Infection
Drug: TMC125; darunavir; ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Study to Evaluate the Pharmacokinetic Profile and Safety of TMC125 Plus Tenofovir DF/Emtricitabine All Dosed Once Daily With and Without Darunavir (PREZISTA™)/ Ritonavir Once Daily in Antiretroviral naïve HIV-1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by Tibotec, Inc:

Primary Outcome Measures:
  • Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia [ Time Frame: Day 1 through 42 and Week 48 ] [ Designated as safety issue: Yes ]

    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.


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

    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.


  • Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin [ Time Frame: Day 1 through 42 and Week 48 ] [ Designated as safety issue: Yes ]

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

    Normal Range: 3.0 - 27.0 ulU/mL


  • Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral [ Time Frame: Day 1 through 42 and Week 48 ] [ Designated as safety issue: Yes ]

    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.


  • 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 ] [ Designated as safety issue: Yes ]

    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


  • 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 ] [ Designated as safety issue: Yes ]

    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.


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

    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.


  • Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) [ Time Frame: Day 8, 14, 22, 28, 42 and Week 48 ] [ Designated as safety issue: No ]
    Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case).

  • 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 ] [ Designated as safety issue: No ]
    Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case).

  • 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 ] [ Designated as safety issue: No ]
    CD4+ Cell Count (x 10^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case).

  • 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 ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: January 2008
Study Completion Date: March 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
TMC125; darunavir; ritonavirTMC125 400mg once daily for 4 weeks; Darunavir-800mg once daily for 48 weeks; Ritonavir-100mg once daily for 48 weeks
Drug: TMC125; darunavir; ritonavir
TMC125 400mg once daily for 4 weeks; Darunavir-800mg once daily for 48 weeks; Ritonavir-100mg once daily for 48 weeks

Detailed Description:

This is a multi-center, open-label (doctors and patients know which drug is being given), Phase IIa clinical trial to evaluate the pharmacokinetic (PK) profile, safety and tolerability of TMC125 dosed once daily with tenofovir/emtricitabine with and without darunavir/ritonavir in antiretroviral naive HIV-1 infected patients. There will be an optional open-label extension phase to evaluate effectiveness, safety and tolerability of continued tenofovir/emtricitabine with darunavir/ritonavir all dosed once daily for 48 weeks. This study will be conducted in the United States at up to 5 sites where 20 patients will initially receive TMC125 400mg with tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily for 14 days. On Day 15, a blood sample will be obtained and intensive TMC125 pharmacokinetic (PK) values and fasting lipids (check of total cholesterol, direct LDL, HDL, triglycerides) following a 10 hour fast (no eating) will be assessed. Patients will then add darunavir / ritonavir 800/100 mg once a day to the regimen for Days 15 - 29. On Day 29 intensive PK sampling for TMC125, darunavir and ritonavir will be performed and fasting lipids will be evaluated. On Day 29, patients will discontinue TMC125 and continue darunavir/ritonavir 800/100 mg and tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily. On Day 43, fasting lipids will be assessed. At this point, patients may enter the optional open-label extension phase of the study and continue treatment with darunavir/ritonavir 800mg/100 mg and tenofovir DF/emtricitabine FDC 300/200mg all dosed once daily through 48 total weeks of treatment. The study will consist of a total of 8 visits including 2 intensive PK visits. Within 4 weeks after the Screening Visit, the study site should have received all data to determine a patient's eligibility for the study. The Baseline Visit (Day 1) will be followed by a study visit on Day 8. An intensive PK visit will occur on Day 15. After modification of therapy on Day 15, a study visit will occur on Day 22. A second intensive PK visit will occur on Day 29. On Day 43 a study visit will occur at which point study therapy will be discontinued unless the patient elects to continue in the optional open label extension phase of the study. Patients electing to continue in the open-label extension will have 4 additional study visits at Week 12, 24, 36 and 48. All patients will be asked to return for a 4-week follow-up visit after the completion of study treatment.

During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for effectiveness and safety will be done at regular visits as well as blood pressure monitoring. All patients will receive TMC125 400 mg orally (by mouth) once daily. Tenofovir DF 300mg/emtricitabine 200mg will be dosed once daily orally as the fixed dose combination. Darunavir/ritonavir will be dosed 800/100 mg orally once daily. All doses should be administered following a meal.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HIV-1 infection
  • Naive to antiretroviral therapy (never received antiretroviral therapy prior to study)
  • In the opinion of the investigator, have an indication for antiretroviral therapy
  • Able to comply with the protocol requirements

Exclusion Criteria:

  • No previous or current use of antiretroviral medications (ARVs) for the treatment of HIV infection or hepatitis B/C infection with anti-HIV activity
  • No evidence of antiretroviral resistance on current or past resistance assays
  • No chronic hepatitis B and/or C co-infection
  • No grade 3 or 4 laboratory abnormality as defined by National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) grading tables, or a calculated creatinine clearance (CLCr) < 50 mL/min.
  • No known diabetes mellitus or hyperlipidemia requiring lipid-lowering therapy
  • No acute viral hepatitis including, but not limited to A, B, or C.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00534352

Sponsors and Collaborators
Tibotec, Inc
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Study Director: Tibotec, Inc. Clinical Trial Tibotec, Inc
  More Information

No publications provided by Tibotec, Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Keywords provided by Tibotec, Inc:
HIV
AIDS
Immunodeficiency Virus, Human
PREZISTA
darunavir
TMC114
TMC125
Protease Inhibitor
Non-Nucleoside Reverse Transcriptase Inhibitor
Truvada
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Tenofovir
Etravirine
Ritonavir
Darunavir
Emtricitabine
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 25, 2014