A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00128830
First received: August 8, 2005
Last updated: June 10, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to evaluate the long-term safety and tolerability of etravirine, administered as part of an individually optimized antiretroviral therapy (ART), in human immunodeficiency virus Type 1 (HIV-1) infected participants.


Condition Intervention Phase
Human Immunodeficiency Virus Type 1
Drug: Etravirine (ETR)
Drug: Nucleotide reverse transcriptase inhibitors (NRTIs)
Drug: Protease inhibitors (PIs)
Drug: Enfuvirtide (ENF)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Trial With TMC125 in HIV-1 Infected Subjects, Who Were Randomized to a TMC125 Treatment Arm in a Sponsor-Selected TMC125 Trial and Were Treated for at Least 48 Weeks

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Number of participants who reported at least 1 of the adverse events.


Secondary Outcome Measures:
  • Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Number of participants who had viral load more than or equal to 50 copies/mL and less than 50 copies/mL at TMC125-C229 baseline and who achieved virologic response (ie, viral load less than 50 copies/mL) at Week 48. The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.

  • Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Number of participants who had viral load more than or equal to 50 copies/mL and less than 50 copies/mL at TMC125-C229 baseline and who achieved virologic response (ie, viral load less than 50 copies/mL) at Week 96. The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.

  • Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL; Less Than 400 Copies/mL; and Greater Than or Equal to 1 Log 10 Decrease From Baseline) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).

  • Number of Participants Who Achieved Virologic Response (ie, Viral Load Less Than 50 Copies/mL; Viral Load Less Than 400 Copies/mL; and Greater Than or Equal to 1 log10 Decrease From Baseline) at Week 192 [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
    Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).

  • Median Change From TMC125-C229 Basline in Cluster of Differentiation 4 (CD4+) Cell Count at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.

  • Median Change From TMC125-C229 Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The last visit of the TMC125 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies) was considered to be the TMC125-C229 baseline.

  • Median Change in Cluster of Differentiation 4 (CD4+) Cell Count From Baseline in TMC125-C229 Feeder Study at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).

  • Median Change in Cluster of Differentiation 4 (CD4+) Cell Count From Baseline in TMC125-C229 Feeder Study at Week 192 [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
    Baseline considered for this outcome is the baseline in the respective TMC125-C229 feeder study (TMC125-C203 [NCT00412646], TMC125-C223 [NCT00081978], TMC125 C211 [NCT00111280] or TMC125-C209 feeder studies).

  • Number of Participants With Emerging Mutation (Reverse Transcriptase Mutation) [ Time Frame: Baseline and Endpoint (ie, the last available time point during the treatment period) ] [ Designated as safety issue: No ]
    Emerging mutations are the mutation which are not present at baseline (last visit of the TMC125 feeder study [TMC125-C203 (NCT00412646), TMC125-C223 (NCT00081978), TMC125 C211 (NCT00111280) or TMC125-C209 feeder studies]) and are present at endpoint (last available timepoint during treatment period for each individual participant).


Enrollment: 211
Study Start Date: June 2005
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etravirine + 2 antiretrovirals Drug: Etravirine (ETR)
Participants will receive 800 mg of ETR (2 x 4 tablets of formulation TF035) twice daily and after the formulation switch they will receive 200 mg of ETR (2 x 2 tablets of formulation F060) twice daily until the participants benefitted from etravirine or it became comercially available.
Other Name: TMC125
Drug: Nucleotide reverse transcriptase inhibitors (NRTIs)
Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).
Drug: Protease inhibitors (PIs)
Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).
Drug: Enfuvirtide (ENF)
Participants will receive 2 additonal approved antiretrovirals (ARVs) along with ETR. ARVs may be NRTIs and/or allowed protease inhibitors (PIs) and/or enfuvirtide (ENF).

Detailed Description:

This is a Phase II, open-label (all people know the identity of the intervention), roll-over study (participants may go ahead and participate in another clinical study). Participants who were randomized (study medication is assigned by chance) to a etravirine (ETR) treatment arm in Phase II TMC125 feeder studies (TMC125-C203, TMC125-C209, TMC125-C223 and TMC125-C211), were treated for at least 48 weeks with etravirine, and who will derive continued benefit from etravirine therapy, as judged by the investigator, will be enrolled in this study. The final visit of the sponsor-selected Phase II ETR study will be the first (baseline) visit of this study. Approximately 300 participants will be enrolled in this study who will receive 800 mg twice daily of etravirine (formulation TF035) until the formulation 200 mg twice daily (formulation F060) is available. Once this formulation becomes available all the participants will be switched to receive F060 which will be given in combination with an investigator-selected, optimized underlying therapy (nucleotide reverse transcriptase [NRTIs] and/or allowed protease inhibitors and/or enfuvirtide). Participants will continue to receive ETR until they are no longer benefitted or this medication becomes commercially available. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants who were previously randomized to an etravirine (ETR) treatment arm and have completed at least 48 weeks of treatment with ETR
  • Participants who will be able to comply with the protocol requirements
  • Participants general medical condition should not interfere with the assessments and the completion of the study

Exclusion Criteria:

  • Use of disallowed concomitant therapy unless a prior exemption had been granted
  • Participant with any treatment-emergent condition or exacerbation of underlying condition during original Phase II study
  • Agrees to protocol-defined use of effective contraception
  • Participant with a grade 3 elevation of amylase and/or lipase except for isolated grade 3 increases of amylase with lipase in normal range and no history of pancreatitis
  • Participant with any grade 4 toxicity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading table; with the exception of grade 4 elevations of triglycerides or glucose asymptomatic or under non-fasting conditions; grade 4 elevation of glucose in participants with pre-existing diabetes
  • Participants with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (International Normalized Ratio [INR] more than 1.5 or albumin less than 30g/l or bilirubin more than 2.5 x upper limit of normal)
  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: NCT00128830

Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

Additional Information:
No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00128830     History of Changes
Obsolete Identifiers: NCT00980772
Other Study ID Numbers: CR002731, TMC125-C229
Study First Received: August 8, 2005
Results First Received: February 27, 2013
Last Updated: June 10, 2013
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Human Immunodeficiency Virus Type 1
HIV-1 infection
TMC125
Etravirine
Enfuvirtide
Antiretroviral therapy

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

ClinicalTrials.gov processed this record on July 24, 2014