TMC114-C227: A Study to Evaluate the Effectiveness and Safety of TMC114 (Darunavir) With a Low Dose of Ritonavir as Monotherapy (no Other Anti-HIV Drugs Will be Given) in Patients Who Have Never Been Treated With Antiretrovirals (Anti-HIV Drugs) Previously

Condition(s) targeted: HIV Infections

Intervention: TMC114 (darunavir) / ritonavir (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Tibotec Pharmaceuticals Limited, Ireland

Official(s) and/or principal investigator(s):
Tibotec Pharmaceuticals Limited Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceuticals Limited, Ireland

This is an open label study (no placebos are used; all patients will receive the true medication) to evaluate the effectiveness of TMC114/rtv in treatment naïve (never previously received anti-HIV drugs), HIV 1 infected patients.

Official title: A Phase II, Open Label Trial in Treatment naïve, HIV 1 Infected Subjects Who Will Receive TMC114/Rtv as a Monotherapy

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: The primary objective is to evaluate sustained anti-viral activity of TMC114/rtv monotherapy in treatment naive, HIV 1 subjects defined by decrease of >1 log viral load (VL) at week 4, VL <400 copies/ml at week 8 and VL< 50 copies/ml at weeks 24 and 48.

Secondary outcome: The secondary objectives are to evaluate safety and tolerability of TMC114/rtv over 48 weeks, to evaluate immunologic response, to evaluate the possible development of resistance and to monitor potential changes in body shape.

Detailed description: This is an open label (no placebo), uncontrolled (all patients will receive TMC114 with ritonavir at the same dose, trial to investigate the sustained anti-viral activity of TMC114/rtv monotherapy in 24 treatment naïve, HIV 1 infected patients over a period of 48 weeks. TMC114, 800 mg daily (2 tablets of 400 mg [F021]) will be given together with 1 capsule (100 mg) of ritonavir. Initially 11 subjects (Panel A, screening viral load between 10000 and 100000 copies/mL) will be included and followed for 8 weeks. If after 8 weeks of dosing at least 7 subjects virologically respond (viral load <400 copies/mL), 13 additional patients (Panel B) will be included. If no virologic failure is observed in at least 18 out of 24 patients who complete 8 weeks of dosing, the trial will continue as planned. In case more than 6 patients in Panel A and Panel B develop a virologic failure after 8 weeks of treatment, the trial will be stopped to conclude the treatment is not effective. The 13 additional patients enrolled in Panel B should have a screening viral load between 20000 and 500000 copies/mL. The CD4+ cell count in all 24 patients should be > 100 cells/µL at screening. The patient's medical condition, adverse events (side effects), study medication compliance, and laboratory evaluations for effectiveness and safety will be assessed at regular intervals. At the end of the 48 weeks treatment period patients will be followed for an additional 4 weeks to evaluate any side effects or laboratory abnormalities. Treatment with TMC114/rtv will be extended for all patients who continue to benefit after 48 weeks.

2 oral tablets of TMC114 400 mg will be administered once daily with 1 capsule (100mg) of ritonavir for 48 weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients with documented HIV-1 infection

- For the first 11 subjects (Panel A), screening plasma HIV-1 viral load is ≥10000

copies/mL and <100000 copies/mL

- For the second set of 13 patients (Panel B), plasma HIV-1 viral load is ≥20000

copies/mL and <500000 copies/mL

- Patients with CD4+ cell count above 100 cells/µl

- Patients have voluntarily signed the ICF

- Patients can comply with the protocol requirements

- Patient's general medical condition, 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 (Category C conditions

according to the CDC Classification System for HIV Infection 1993) with some exceptions

- Previous or current use of antiretroviral (ARVs/anti-HIV drugs) (including both

investigational as well as commercially available ARVs indicated for the treatment of HIV-infection and ARVs for treatment of hepatitis B infection with anti-HIV activity (e. g., adefovir)

- Having one of protocol listed 1 PI, NRTI, or NNRTI resistance associated mutation at

screening

- Patients with primary HIV infection

- Female patients of childbearing potential without use of effective non-hormonal birth

control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period

- Any active clinically significant disease (e. g., abnormal heart function,

pancreatitis, acute viral infection) or findings during screening of medical history or physical examination that are expected to compromise the patient's safety or outcome in the trial

Buenos Aires C1141ACG, Argentina

Buenos Aires C1202ABB, Argentina

Starting date: September 2006
Ending date: October 2007
Last updated: April 24, 2008