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.

• Status: Completed
• Trial end date: 2007-07-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tibotec Pharmaceuticals, Ireland
• Treatments: Darunavir

Criteria

Inclusion Criteria:

• 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

• 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.

Exclusion Criteria:

• 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)

• 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.