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Phase II Study on the Antiviral Activity and Safety of BILR 355 BS in HIV-1 Infected, NNRTI-Treated Patients
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This study is not yet open for patient recruitment.
Verified by Boehringer Ingelheim Pharmaceuticals February 2006 Sponsored by: Boehringer Ingelheim Pharmaceuticals
Purpose
The purpose of this Phase IIa, randomized, double-blind, placebo-controlled trial is to investigate the antiviral effect, safety and tolerability of seven days of monotherapy of BILR 355 BS, followed by 28 days of combination therapy with a Tipranavir- or Lopinavir-based HAART regimen. Additional assessment to be evaluated in this trial include: changes in the HIV-1 genotype, drug susceptibility, and the pharmacokinetics of BILR 355 BS.
BILR 355 BS is a non-nucleoside reverse transcriptase inhibitor (NNRTI). BILR 355 BS will be given with a low dose of Ritonavir (RTV) during the monotherapy periode. After screening, patients will stop their currently failing HAART-therapy for 28 days (washout). Patients will be randomized in a 1:1:1 allocation to BILR 355 BS 75mg twice daily, 150mg twice daily or matching Placebo. After the wash-out period (Day 0), patients initiate either BILR 355 BS/RTV or Placebo/RTV for 7 days of monotherapy to evaluate the antiviral activity of BILR 355 BS. All patients will take two BILR 355 BS or matching Placebo tablets twice daily in combination with one capsule RTV(100 mg) once daily. On Day 8, all patients will add a standard PI-based HAART regimen. Background PI-therapy will be RTV-boosted Tipranavir (TPV/r) or Lopinavir (LPV/r). The NRTI-backbone will be optimised based on prior exposure and actual resistance testing results. The combination of BILR 355 BS or Placebo and the PI-based HAART will be given for 28 days to evaluate the safety profile of BILR 355 BS. On Day 35, BILR 355 BS or Placebo will be stopped. The TPV/r- or LPV/r-based HAART will be continued as the further standard treatment for the patient after the termination of the study medication. A final follow-up visit will occur 28 days after completion of study medication dosing. The trial will involve a screening period of up to 6 weeks, a 5-week treatment period, and a 4-week follow-up period.
Study Design:
Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment
Official Title: Randomized, Double-Blind, Double-Dummy, Placebo-Controlled 7 Day Monotherapy Phase IIa Study to Evaluate the Antiviral Activity and Safety of Oral Administered RTV-Boosted BILR 355 (75 Mg and 150 Mg Twice Daily) inHIV-1-Infected, NNRTI-Experienced Patients, Followed by 28 Day Combination Therapy With Tipranavir or Lopinavir Based HAART-Regimen
Further study details as provided by Boehringer Ingelheim Pharmaceuticals:
Primary Outcomes: The primary endpoint will be reduction in plasma HIV-1 RNA from baseline to day 8, expressed in log10 copies/mm3.
Secondary Outcomes: Incidence of rash, hepatic events, and CNS adverse events Incidence of any adverse events and serious adverse events Incidence of laboratory test abnormalities
Expected Total Enrollment: 36
Study start: February 2006; Expected completion: June 2007
Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both
Criteria
Inclusion Criteria:
1. Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation.
2. HIV-1 infected males or females >= 18 years of age.
3. History of NNRTI based HAART >= 8 weeks and at least one, but not more than 3 NNRTI-associated resistance mutations by current genotype
4. TPV/r or LPV/r susceptible
5. CD4+ T lymphocyte count >= 100 cells/ml.
7. HIV-1 viral load >= 2000 copies/mL at screening.
8. Karnofsky score >= 70
9. Based on the antiviral resistance profile of the patients virus, the investigator must be able to construct a background HAART treatment regimen (OBR) such that the patient will receive 3 effective ARV drugs, in addition to his study medication.
10. Acceptable screening laboratory values (Visit 1) that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply: Absolute neutrophil count (ANC) >750/mm3 Hemoglobin >= 10 g/dL Platelet count >99,000/mm3 AST, ALT , and alkaline phosphatase < 2.5xULN >= DAIDS Grade 1) Total bilirubin <2.5xULN Serum amylase <1.5xULN
11. Acceptable medical history, as assessed by the investigator, with chest x-ray results and ECG within 1 year of study participation.
12. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system 13. A prior AIDS defining event, excluding mycobacterial and invasive fungal infections, is acceptable as long as it has resolved or the subject has been on stable treatment (e.g. opportunistic infection) for at least 12 weeks before screening (Visit 1). Note that prior oral thrush, candida esophagitis and cutaneous candida is acceptable.
Exclusion Criteria:
1. The following resistance mutations demonstrated at any time prior to starting trial therapy: V106A and/or Y188L
2. Female patients of child-bearing potential who:
--have a positive serum pregnancy test at screening or during the study, are breast feeding, are planning to become pregnant, are not willing to use a barrier method of contraception.
3. Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT > DAIDS Grade 1
4. Acute/previous mycobacterial or invasive fungal infection requiring therapy or prophylaxis with drugs interfering with or significantly affected by the cytochrome P450 system
5. Use of investigational medications within 30 days before study entry or during the trial.
6. Use of concomitant drugs that may significantly reduce plasma levels of the study medications.
7. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
8. Patients currently treated with systemic ant-cancer chemotherapy
9. Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator.
10. In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00294372
Boehringer Ingelheim Study Coordinator +49 (7351) 54-5064
Epimed GmbH, Berlin, Germany
St. Josef-Hospital, Bochum, Germany
Medizinische Poliklinik, Germany
Universitatsklinikum Ulm, Ulm, Germany
ifi Institut fur interdisziplinare Infektiologie, Hamburg, Germany
Medizinische Universitatsklinik Bonn, Bonn, Germany
Med. Hochschule Hannover, Hannover, Germany
Klinikum der J.-W.-Goethe-Universitat, Frankfurt/Main, Germany
Universitatsklinik Hamburg-Eppendorf, Hamburg, Germany
Universitatsklinikum Heidelberg, Heidelberg, Germany
Universitatsklinik Erlangen-Nurnberg, Erlangen, Germany
Study chairs or principal investigators
Boehringer Ingelheim Study Coordinator
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