HIVPhase 2NCT00650832
TMC114-C213: A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-response of TMC114/RTV in 3-class-experienced HIV-1 Infected Patients, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.
A Phase 2 study testing TMC114; darunavir; Prezista in people with HIV, run by Tibotec Pharmaceuticals, Ireland.
Trial summary
The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- TMC114; darunavir; Prezista
- How many people
- 334 participants
- Where
- No sites listed yet
- Study dates
- Oct 2003to Jul 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with documented HIV-1 infection
- Patients receiving a PI-containing regimen at screening initiated at least 8 weeks prior to screening with plasma HIV-1 RNA > 1000 copies/mL
- Prior use of more than 1 NRTI for at least 3 months in total
- Prior use of one or more NNRTIs (investigational included) as part of a failing regimen
- Patients having at least 1 primary PI mutation at screening as defined by the IAS guidelines (D30N, M46I/L, G48V, I50V/L, V82A/F/T/S, I84V, L90M)16
- patients experienced to at least one PI for a total period of at least 3 months
Show all 9Show fewer
- Patients voluntarily signs the informed consent form
- Patients can comply with the protocol requirements
- Patients having a general medical condition that, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.
Who cannot join
- Presence of any currently active AIDS defining illness with the following exceptions, which must be discussed with the sponsor prior to enrollment: Stable cutaneous Kaposi's Sarcoma (i.e. no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial. Wasting syndrome due to HIV infection if, in the investigator's opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the patient's safety or compliance to adhere to the study protocol procedures. If patients are on maintenance therapy (which may include human Growth Hormone, appetite stimulants and anabolic steroids) for previously diagnosed wasting, they may be eligible for the trial only if such treatment is not included in the list of disallowed medications
- Current or past history of alcohol and/or drug use which, in the investigator's opinion, would compromise the patient's safety or compliance to the study protocol procedures
- patients on a treatment interruption at screening
- patients for whom an investigational ARV is part of the regimen at screening, (with the following exceptions: T-20, FTC, atazanavir and fos-amprenavir) or use of any other non-ARV investigational agents at least 90 days prior to screening
- Use of disallowed concomitant therapy
- Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC114/RTV/placebo)
Show all 22Show fewer
- Life expectancy of less than 6 months
- Pregnant or breast feeding
- Female patient of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until at least 14 days after the end of the treatment period
- Patients with clinical or laboratory evidence of active liver disease, liver impairment/dysfunction or cirrhosis irrespective of liver enzyme levels
- Any active or unstable medical condition (e.g. TB
- cardiac dysfunction
- acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patients safety or outcome of the study
- Patients with the following laboratory abnormalities as defined by ACTG grading scheme Renal impairment: serum creatinine grade 2 or greater (> 1.5 x ULN)
- Lipase grade 2 or greater (> 1.5 x ULN)
- Hemoglobin toxicity grade 2 or greater (£ 7.9 g/dL)
- Platelet count grade 2 or greater (< 75000/mm³)
- Absolute neutrophil count grade 2 or greater (£ 999/mm3)
- ALT, AST grade 2 or greater (>2.5 x ULN)
- Total bilirubin grade 2 or greater (> 1.5 x ULN) unless clinical assessment foresees an immediate health risk to the patient. For patients receiving indinavir or atazanavir at screening the total bilirubin may not exceed 3 x ULN
- Any grade 3 or 4 toxicity with the following exceptions unless clinical assessment foresees an immediate health risk to the patient: Patients with pre-existing diabetes or assessments under non-fasted conditions who experienced a glucose grade 3 or 4, Patients with triglyceride or cholesterol elevation of grade 3 or 4 under non-fasted conditions, Patients who experienced asymptomatic triglyceride or cholesterol elevations of grade 3 or 4, patients who experienced an asymptomatic and isolated GGT grade 3 or 4 elevation with all other LFTs and bilirubin within normal ranges
- Patients who have been randomized to a TMC114 treatment arm in a previous TMC114 trial.
About this study
Official title: A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-response of TMC114/RTV in 3-class-experienced HIV-1 Infected Subjects, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.
The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir
Read the detailed description
This trial consists of two parts: a partially blinded dose-finding part followed by an open-label part with the recommended dose of TMC114/RTV. The dose-finding part of this trial consisted of a randomized controlled (standard of care), partially blinded, Phase II trial to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir. The pharmacokinetics of TMC114 are also assessed.Three hundred HIV-1 infected patients who were three-class-experienced and who were on a stable PI-containing regimen at screening for at least 8 weeks and who had plasma HIV-1 RNA > 1000 copies/mL were eligible. Three-class experience was defined as prior treatment with ³ 2 NRTIs for at least 3 months in total and ³ 1 NNRTI as part of a failing regimen. In addition, patients had to have received at least one PI for at least 3 months in the past and had to have at least 1 primary PI mutation (according to IAS definitions) at screening.As soon as all results to determine eligibility were available, and no later than 2 weeks prior to the baseline visit, the patients were randomized to one of 4 TMC114/RTV treatment groups or to a control group (standard of care). At baseline, patients changed to an investigator selected PI(s) regimen or TMC114/RTV plus optimized background regimen (OBR) consisting of NRTIs with or without T-20.In the dose-finding part of the trial, the primary objective of the trial was to evaluate the dose-response relationship in antiviral activity between the TMC114 /RTV treatment groups at 24 weeks. The recommended dose has been selected based on two joint interim analyses of this trial and of a similar trial (TMC114-C202, conducted in the United States of America, Puerto Rico, and Argentina) including approximately 150 patients in each of the two dose-finding trials (TMC114-C202 + TMC114-C213) who reached Weeks 16 and 24 or dropped out earlier. The Week 24 interim analysis included a total of 497 patients, of whom 329 had reached Week 24 or discontinued earlier. Based on the results of these two joint interim analyses, TMC114/RTV 600/100 mg b.i.d. was selected as the recommended dose for the open-label part of this trial and for future trials in treatment-experienced HIV-1 infected patients. The recommended dose of TMC114/RTV was not communicated to the investigators until the data cut-off date for the primary efficacy analysis of the two dose-finding trials was reached.The primary efficacy analysis was performed when approximately 300 patients in this trial reached 24 weeks of treatment or discontinued earlier (i.e., the primary endpoint, which was reached on 1 February 2005; A total of 318 patients were included in the analysis of whom 301 reached Week 24 or discontinued earlier). In this primary efficacy analysis, all TMC114 groups were compared to the control group by means of the confirmed virologic response at Week 24, defined as a drop in viral load of at least 1 log10 versus baseline. This primary efficacy analysis confirmed that TMC114/RTV 600/100 mg b.i.d. is the recommended dose for treatment-experienced HIV-1 infected patients.After the primary endpoint of the trial was reached (1 February 2005), and after approval of the related protocol amendment by the relevant IEC/IRB and authorities, the patients in the TMC114/RTV groups were instructed to switch to the recommended dose of TMC114/RTV (600/100 mg b.i.d.) in the open-label part of the trial.In addition, long term safety, tolerability and the durability of antiviral activity of TMC114/RTV over 144 weeks in 3-class-experienced HIV-1 infected patients will be evaluated. The trial includes a screening period of a maximum of 6 weeks, and a 144-week treatment period followed by a 4-week follow-up period. The maximum duration of the trial will be 154 weeks.Tibotec will provide follow-up treatment with TMC114/RTV for all patients who continue to benefit from treatment with TMC114/RTV. TMC114 will be provided until the drug is commercially available or until its development is discontinued.The patient will remain on the study until he/she no longer benefits from TMC114/RTV, as judged by the investigator, or he/she meets one of the withdrawal criteria. Dose-finding part of the trial: 400 mg/100 mg q.d. TMC114/RTV or 800 mg/100 mg q.d. TMC114/RTV or 400 mg/100 mg b.i.d. TMC114/RTV or 600 mg/100 mg b.i.d. TMC114/RTV. Open-label part of the trial: 600 mg/100 mg b.i.d. TMC114/RTV. Total treatment duration of 144 weeks.
- Conditions
- HIV
- Being tested
- TMC114; darunavir; Prezista
- Keywords
- HIV, anti-infectives
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC114; darunavir; PrezistaDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of the trial is to compare all TMC114/RTV dose groups with control at Week 24 (the primary endpoint) by means of the confirmed virologic response, defined as a drop in viral load of at least 1 log10 versus baseline.
Secondary outcomes (1)
To evaluate safety and tolerability over 24 to 144 weeks; To evaluate the durability of the antiviral activity; To investigate the dose-response by comparing the different TMC114/RTV dosages.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2008 (estimated)
- Study startOct 2003
- Primary completionFeb 2005
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Enrolment
- 334 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Tibotec Pharmaceuticals Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00650832
- Sponsor's protocol ID
- CR006775
- Status last verified
- Jun 2011
- First submitted
- 28 Mar 2008
- Last updated
- 15 Jun 2011
- Results posted
- No
Publications
Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wohrmann A, Katlama C, Wilkin T, Haubrich R, Cohen C, Farthing C, Jayaweera D, Markowitz M, Ruane P, Spinosa-Guzman S, Lefebvre E; POWER 1 and 2 study groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet. 2007 Apr 7;369(9568):1169-78. doi: 10.1016/S0140-6736(07)60497-8.
PubMed 17416261
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-response of TMC114/RTV in 3-class-experienced HIV-1 Infected Subjects, Followed by an Open-label Period on the Recommended Dose of TMC114/RTV.
- ClinicalTrials.gov ID
- NCT00650832
- Acronym / sponsor ID
- CR006775
- Conditions
- HIV
- Keywords
- HIV, anti-infectives
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 334 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Oct 2003
- Primary completion
- Feb 2005 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 2 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir
Detailed description
This trial consists of two parts: a partially blinded dose-finding part followed by an open-label part with the recommended dose of TMC114/RTV. The dose-finding part of this trial consisted of a randomized controlled (standard of care), partially blinded, Phase II trial to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir. The pharmacokinetics of TMC114 are also assessed.Three hundred HIV-1 infected patients who were three-class-experienced and who were on a stable PI-containing regimen at screening for at least 8 weeks and who had plasma HIV-1 RNA > 1000 copies/mL were eligible. Three-class experience was defined as prior treatment with ³ 2 NRTIs for at least 3 months in total and ³ 1 NNRTI as part of a failing regimen. In addition, patients had to have received at least one PI for at least 3 months in the past and had to have at least 1 primary PI mutation (according to IAS definitions) at screening.As soon as all results to determine eligibility were available, and no later than 2 weeks prior to the baseline visit, the patients were randomized to one of 4 TMC114/RTV treatment groups or to a control group (standard of care). At baseline, patients changed to an investigator selected PI(s) regimen or TMC114/RTV plus optimized background regimen (OBR) consisting of NRTIs with or without T-20.In the dose-finding part of the trial, the primary objective of the trial was to evaluate the dose-response relationship in antiviral activity between the TMC114 /RTV treatment groups at 24 weeks. The recommended dose has been selected based on two joint interim analyses of this trial and of a similar trial (TMC114-C202, conducted in the United States of America, Puerto Rico, and Argentina) including approximately 150 patients in each of the two dose-finding trials (TMC114-C202 + TMC114-C213) who reached Weeks 16 and 24 or dropped out earlier. The Week 24 interim analysis included a total of 497 patients, of whom 329 had reached Week 24 or discontinued earlier. Based on the results of these two joint interim analyses, TMC114/RTV 600/100 mg b.i.d. was selected as the recommended dose for the open-label part of this trial and for future trials in treatment-experienced HIV-1 infected patients. The recommended dose of TMC114/RTV was not communicated to the investigators until the data cut-off date for the primary efficacy analysis of the two dose-finding trials was reached.The primary efficacy analysis was performed when approximately 300 patients in this trial reached 24 weeks of treatment or discontinued earlier (i.e., the primary endpoint, which was reached on 1 February 2005; A total of 318 patients were included in the analysis of whom 301 reached Week 24 or discontinued earlier). In this primary efficacy analysis, all TMC114 groups were compared to the control group by means of the confirmed virologic response at Week 24, defined as a drop in viral load of at least 1 log10 versus baseline. This primary efficacy analysis confirmed that TMC114/RTV 600/100 mg b.i.d. is the recommended dose for treatment-experienced HIV-1 infected patients.After the primary endpoint of the trial was reached (1 February 2005), and after approval of the related protocol amendment by the relevant IEC/IRB and authorities, the patients in the TMC114/RTV groups were instructed to switch to the recommended dose of TMC114/RTV (600/100 mg b.i.d.) in the open-label part of the trial.In addition, long term safety, tolerability and the durability of antiviral activity of TMC114/RTV over 144 weeks in 3-class-experienced HIV-1 infected patients will be evaluated. The trial includes a screening period of a maximum of 6 weeks, and a 144-week treatment period followed by a 4-week follow-up period. The maximum duration of the trial will be 154 weeks.Tibotec will provide follow-up treatment with TMC114/RTV for all patients who continue to benefit from treatment with TMC114/RTV. TMC114 will be provided until the drug is commercially available or until its development is discontinued.The patient will remain on the study until he/she no longer benefits from TMC114/RTV, as judged by the investigator, or he/she meets one of the withdrawal criteria. Dose-finding part of the trial: 400 mg/100 mg q.d. TMC114/RTV or 800 mg/100 mg q.d. TMC114/RTV or 400 mg/100 mg b.i.d. TMC114/RTV or 600 mg/100 mg b.i.d. TMC114/RTV. Open-label part of the trial: 600 mg/100 mg b.i.d. TMC114/RTV. Total treatment duration of 144 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with documented HIV-1 infection
- Patients receiving a PI-containing regimen at screening initiated at least 8 weeks prior to screening with plasma HIV-1 RNA > 1000 copies/mL
- Prior use of more than 1 NRTI for at least 3 months in total
- Prior use of one or more NNRTIs (investigational included) as part of a failing regimen
- Patients having at least 1 primary PI mutation at screening as defined by the IAS guidelines (D30N, M46I/L, G48V, I50V/L, V82A/F/T/S, I84V, L90M)16
Key exclusion criteria (22 listed)
- Presence of any currently active AIDS defining illness with the following exceptions, which must be discussed with the sponsor prior to enrollment: Stable cutaneous Kaposi's Sarcoma (i.e. no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial. Wasting syndrome due to HIV infection if, in the investigator's opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the patient's safety or compliance to adhere to the study protocol procedures. If patients are on maintenance therapy (which may include human Growth Hormone, appetite stimulants and anabolic steroids) for previously diagnosed wasting, they may be eligible for the trial only if such treatment is not included in the list of disallowed medications
- Current or past history of alcohol and/or drug use which, in the investigator's opinion, would compromise the patient's safety or compliance to the study protocol procedures
- patients on a treatment interruption at screening
- patients for whom an investigational ARV is part of the regimen at screening, (with the following exceptions: T-20, FTC, atazanavir and fos-amprenavir) or use of any other non-ARV investigational agents at least 90 days prior to screening
- Use of disallowed concomitant therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC114; darunavir; Prezista | Drug | – |
Primary outcome
The primary objective of the trial is to compare all TMC114/RTV dose groups with control at Week 24 (the primary endpoint) by means of the confirmed virologic response, defined as a drop in viral load of at least 1 log10 versus baseline.
1 secondary outcome
To evaluate safety and tolerability over 24 to 144 weeks; To evaluate the durability of the antiviral activity; To investigate the dose-response by comparing the different TMC114/RTV dosages.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2011.
- Results publication: PubMed 17416261Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wohrmann A, Katlama C, Wilkin T, Haubrich R, Cohen C, Farthing C, Jayaweera D, Markowitz M, Ruane P, Spinosa-Guzman S, Lefebvre E; POWER 1 and 2 study groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet. 2007 Apr 7;369(9568):1169-78. doi: 10.1016/S0140-6736(07)60497-8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals Clinical Trial study director
Tibotec Pharmaceutical Limited
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TMC114; darunavir; Prezista in people with HIV, run by Tibotec Pharmaceuticals, Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective of the trial is to compare all TMC114/RTV dose groups with control at Week 24 (the primary endpoint) by means of the confirmed virologic response, defined as a drop in viral load of at least 1 log10 versus baseline.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00650832, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2011.