TMC114-C226: An Early Access Program to Evaluate the Long-term Safety and Tolerability of TMC114 Combined With a Low Dose of Ritonavir ("TMC114/r") With Other Antiretrovirals, for HIV-1 Infected Patients Who Have Failed Multiple Antiretroviral Regimens. - Full Text View

Sponsor:	Tibotec Pharmaceuticals, Ireland
Information provided by:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00245739

Purpose

The purpose of this study is to provide early access to TMC114 (a protease inhibitor) for HIV-1 infected patients with limited or no treatment options, who have failed multiple antiretroviral (ARV) regimens, and to evaluate the longer-term safety and tolerability of TMC114/r in combination with other antiretrovirals

Condition	Intervention	Phase
HIV Infections	Drug: TMC-114	Phase III

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study
Official Title:	Early Access of TMC114 in Combination With Low-dose Ritonavir (TMC/r)) and Other Antiretrovirals (ARVs) in Highly Treatment Experienced HIV-1 Infected Patients With Limited to no Treatment Options.

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:

Evaluation of safety and tolerability of TMC114/r with other antiretrovirals [ Time Frame: Expected Time Frame is end 2009. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The secondary objective is to gather information on the safety and tolerability of TMC114 in combination with low-dose RTV and other ARVs during the course of this study. [ Time Frame: Expected Time Frame is end 2009, depending availability of Prezista to patients. ] [ Designated as safety issue: Yes ]

Enrollment:	2960
Study Start Date:	October 2005
Study Completion Date:	September 2009
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
001: Experimental TMC-114600/100 mg tablets of TMC114/rtv BID until commercial available to the subject	Drug: TMC-114 600/100 mg tablets of TMC114/rtv BID until commercial available to the subject

Detailed Description:

This is a program to provide early access to TMC114 (a protease inhibitor) for HIV-1 infected patients, who have failed multiple antiretroviral (ARV) regimens and who are ineligible for participation in any other Tibotec-sponsored HIV trial. Patients need to be at least 3 class experienced (PIs, NRTIs, NtRTIs, NNRTIs or FI), to have previously received 2 different protease inhibitor-based regimens and to not be virologically suppressed on their current regimen. Patients eligible for any other Tibotec sponsored HIV trial but located more than 100 kilometers away from a study site, will be considered eligible for this early access program.

This program will be conducted as an open-label, non-randomized treatment study. Once treatment with TMC114/r in combination with other antiretrovirals (ARVs) has been initiated (baseline visit), patients will follow the recommended visit schedule based on routine clinical care. No other protease inhibitor combinations other than TMC114/r are to be used in this study, except atazanavir (ATV) and indinavir (IDV) may be allowed. Trial medication will be dispensed every 8 weeks. Treatment with TMC114/r will be continued until treatment-limiting toxicity, loss to follow-up, patient's withdrawal, pregnancy, discontinuation of TMC114 development or when TMC114 has become commercially available.

Selected safety and tolerability data, including adverse events will be collected throughout the study. A urine pregnancy test will be repeated at baseline for female patients if more than 4 weeks have passed since the test at screening, and urine pregnancy tests will be performed at all other visits. In addition, data on CD4 count and viral load will be collected over the treatment period according to local standard of care practice, in order to ensure that patients continue to benefit from treatment with TMC114/r. A final/withdrawal visit as well as a post-trial treatment follow-up contact (4 weeks after the final/withdrawal visit) will be performed. Patients will take oral doses of 600 mg of TMC114 twice daily in combination with 100 mg of ritonavir twice daily, in combination with other antiretrovirals.

Eligibility

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

Criteria

Inclusion Criteria:

Patient with documented HIV-1 infection
has limited or no treatment options due to virological failure or intolerance to multiple antiretroviral regimens
is at least 3 class experienced and has previously received 2 different protease inhibitor-based regimens
has a CD4 cell count <= 200 cells/mm3
is not achieving adequate virologic suppression on his/her current regimen and is at risk of clinical or immunologic progression.

Exclusion Criteria:

Patient has primary HIV-1 infection (unless documented resistance to all currently approved protease inhibitors participated or is currently participating in a trial with TMC114
Patient used investigational medication within the last 30 days (except for abacavir/lamivudine and tenofovir/emtricitabine fixed dose combinations, and tipranavir)
Patient suffers from any active clinically significant disease (e.g., cardiac dysfunction, pancreatitis, acute viral infection) or has evidence of active liver disease, liver impairment/dysfunction or cirrhosis irrespective of liver enzyme levels, or has grade 3 or 4 laboratory abnormalities as defined by National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) grading scheme
Female patients that are pregnant or breast-feeding, or of childbearing potential without using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00245739

Sponsors and Collaborators

Tibotec Pharmaceuticals, Ireland

Investigators

Study Director:

Tibotec Pharmaceuticals Clinical Trial

Tibotec Pharmaceuticals

More Information

No publications provided

Responsible Party:	Tibotec Pharmaceutical Limited ( Compound Development Team Leader TMC114 )
Study ID Numbers:	CR006304, 0034476
Study First Received:	October 27, 2005
Last Updated:	January 21, 2010
ClinicalTrials.gov Identifier:	NCT00245739 History of Changes
Health Authority:	United States: Food and Drug Administration; Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:

HIV
HIV-1
TMC114

Early access
Highly antiretroviral treatment experienced patients
Anti-retroviral agents

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Darunavir
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010