- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00964327
TMC114-C201: A Study to Determine the Antiviral Activity of TMC114 in Patients With Multiple Protease Inhibitor (PI) Resistant Human Immunodeficiency Virus (HIV) Strains
May 18, 2011 updated by: Tibotec Pharmaceuticals, Ireland
A Phase IIa Open-label, Randomized Trial to Determine the Antiviral Activity in 60 HIV Positive Subjects With Multiple PI Resistant Strains, Receiving Either Control Treatment or a Daily Dose of 800, 1600, 2400 or 3600 mg TMC114 (Darunavir) for 13 Days Followed by a Single Dose on Day 14
The purpose of this study is to determine the antiviral activity, safety and tolerability of 14 days of different doses of TMC114 to treat HIV-1 positive patients whose condition is failing on a current treatment regimen that includes a protease inhibitor (PI) (a medication used to reduce the amount of HIV virus in the blood).To be considered for the study, patients must have a documented resistance to at least 2 of the current PIs.
Pharmacokinetics and pharmacodynamics of TMC114 will also be assessed.
Study Overview
Detailed Description
This is a Phase lla open-label (all people involved know the identity of the treatment), randomized (study drug assigned by chance), controlled (the patients of the control group continue the failing regimen), dose-finding study to determine the antiviral activity, safety and tolerability of a 14-day treatment with TMC114 (a protease inhibitor) for treatment of human immunodeficiency virus type 1 (HIV-1) positive patients who are considered resistant to (failing to improve on) 2 or more protease inhibitors (PIs).
Sixty HIV-1 positive patients, who are resistant to multiple PIs as confirmed by specialized testing (virtual phenotyping) and who are currently failing to improve on a treatment regimen that contains a PI, will be randomly assigned to one of 5 treatment groups.
Those randomized to the control group will continue their current therapy (consisting of PIs and Nucleoside Reverse Transcriptase Inhibitor(s) (NRTIs)).
Those randomized to the TMC114 treatment groups will receive the study drug as a substitute for all the PIs in the current failing treatment regimen at the following dose levels: 400 or 800 mg twice a day, or 800 or 1200 mg three times a day for 13 days followed by a single dose on day 14.
The dose of the NRTIs (NRTIs are drugs that suppress replication of retroviruses) will remain unchanged until the end of the treatment period.
The trial will involve a screening period of maximum three weeks, a 7-day run-in period (the period of time before study start when no treatment is given), a 14-day treatment period, followed by a 6- week follow-up period.
The maximal trial duration will thus be twelve weeks.
Primary objective is to determine the antiviral activity of TMC114 as well as the pharmacokinetics (how the drug is absorbed in the body, distributed within the body and how it is removed from the body over time) and pharmacodynamics (the study of the action of effects a drug has on the body) will also be assessed over the 2 week period.Safety will be followed at regular intervals during treatment and follow-up period.
Safety assessments consist of regular lab assessments, ECG recording, vital signs, physical examination, body weight and Body Mass Index.
Observation of and interview for adverse events will be done daily during the first week of treatment, every second day during the 2nd week of treatment, and at week 1, 3 and 6 of the follow-up period.
In addition an Independent Data Monitoring Committee will evaluate the study data at regular intervals.
Patients will be randomly assigned to one of 5 treatment groups: 400 or 800 mg twice a day for 13 days followed by a single dose on day 14, or 800 or 1200 mg three times a day for 13 days followed by a single dose on day 14.
Patients randomized to the control group will continue their current therapy consisting of protease inhibitors (PIs) and Nucleoside Reverse Transcriptase Inhibitors (NRTIs).
Study Type
Interventional
Enrollment (Actual)
42
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient has a documented HIV-1 infection with a viral load at screening visit above 2,000 HIV copies/ml
- Currently treated with a failing antiretroviral regimen consisting of NRTIs together with one or more PI(s)
- Has a resistance against at least 2 of the currently used PIs
- Patient agrees not to change the current therapy until end of run-in and agrees not to change NRTIs until the end of treatment period
- No current AIDS defining illnesses
Exclusion Criteria:
- NNRTI (non-nucleoside reverse transcriptase inhibitor) containing regimen, two weeks prior to screening
- Suspicion of alcohol abuse or drug abuse, leading to non-compliance
- History of significant drug allergy induced by PIs
- CD4 count < 50
- Life expectancy of less than 6 months
- Pregnant or breast feeding females
- Females of childbearing potential without use of a highly effective birth control method or not willing to continue practicing this birth control method for at least 14 days after the end of the treatment
- Received an investigational drug within 30 days prior to the trial drug administration
- Patients with clinically significant laboratory abnormalities.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the antiviral activity of TMC114.
Time Frame: Screening, days -7, -3, 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 , 15, follow-up weeks 1, 3 and 6
|
Screening, days -7, -3, 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 , 15, follow-up weeks 1, 3 and 6
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
nadir of viral load
Time Frame: Screening, days -7, -3, 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 , 15, follow-up weeks 1, 3 and 6
|
Screening, days -7, -3, 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 , 15, follow-up weeks 1, 3 and 6
|
Pharmacokinetics (PK) / Pharmacodynamics (PD): Plasma concentration of TMC114 and efficacy and safety data will be analyzed to find relationships between PK and PD.
Time Frame: 12 visits
|
12 visits
|
CD4 count
Time Frame: 7 visits
|
7 visits
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2001
Primary Completion (Actual)
October 1, 2003
Study Completion (Actual)
October 1, 2003
Study Registration Dates
First Submitted
July 27, 2009
First Submitted That Met QC Criteria
August 20, 2009
First Posted (Estimate)
August 24, 2009
Study Record Updates
Last Update Posted (Estimate)
May 19, 2011
Last Update Submitted That Met QC Criteria
May 18, 2011
Last Verified
April 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Darunavir
Other Study ID Numbers
- CR006718
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
-
Florida International UniversityCompleted
-
Boston Children's HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Completed
Clinical Trials on TMC114
-
Janssen Research & Development, LLCCompleted
-
Tibotec Pharmaceuticals, IrelandCompleted
-
Tibotec Pharmaceuticals, IrelandCompletedHIV InfectionsUnited States, Argentina
-
Tibotec Pharmaceuticals, IrelandCompletedHIV InfectionUnited States, Australia, France, United Kingdom, Germany, Spain, Belgium, Portugal, Canada, Argentina, Brazil, Austria, Hungary
-
Janssen-Cilag International NVCompletedHIV Infections | Human Immunodeficiency Virus | Acquired Immunodeficiency Syndrome Virus | AIDS VirusUnited Kingdom, Belgium, Germany, Spain, Portugal, Israel, Denmark, Russian Federation, Austria, Hungary, Switzerland
-
Tibotec Pharmaceuticals, IrelandCompletedHIV InfectionUnited States, Australia, France, United Kingdom, Belgium, Germany, Spain, Argentina, Chile, Mexico, Portugal, Malaysia, Panama, South Africa, Canada, Netherlands, Brazil, Puerto Rico, Austria, Russian Federation, Thailand, Hungary, Denmar... and more
-
Janssen Research & Development, LLCCompletedHuman Immunodeficiency Virus (HIV)United States, Spain, South Africa
-
Tibotec Pharmaceuticals, IrelandCompletedHIVUnited Kingdom, Germany, Denmark, Belgium, Austria, Poland, Australia, Russian Federation