Phase II Study on the Antiviral Activity and Safety of BILR 355 BS in HIV-1 Infected, NNRTI-treated Patients

This study has been terminated.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00294372
First received: February 20, 2006
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

The general aim is to evaluate the antiviral activity and safety of increasing doses of oral administered RTV-boosted BILR 355 BS (75 mg and 150 mg twice daily) in HIV-1-infected, NNRTI-experienced patients, followed by 28 day combination therapy with Tipranavir or Lopinavir based HAART-regimen


Condition Intervention Phase
HIV Infections
Drug: BILR 355 BS
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomised, Double-blind, Placebo-controlled 7 Day Monotherapy Phase IIa Study to Evaluate the Antiviral Activity and Safety of Increasing Doses of Oral Administered RTV-boosted BILR 355 BS (75 mg and 150 mg Twice Daily) in HIV-1-infected, NNRTI-experienced Patients, Followed by 28 Day Combination Therapy With Tipranavir or Lopinavir Based HAART-regimen

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary endpoint will be reduction in plasma HIV-1 RNA from baseline to day 8, expressed in log10 copies/mm3. [ Time Frame: day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Virologic response at Day 8 and Day 35 using <400 copies/mL and 0.5, 1 and 1.5 log10 reduction in viral load from baseline [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Change from baseline in viral load at each visit [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell counts at each visit [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Time averaged change from baseline in viral load through Days 8 and 35 [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Number of reverse transcriptase (RT) mutations at baseline [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Number of NNRTI resistance-associated mutations at baseline (refer to Appendix 10.4) [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • The presence of specific RT mutations (both in the list of NNRTI mutations and not in the list for exploratory purposes) at baseline [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • The inhibitory quotient and minimum measured concentration of the analyte in plasma (Cmin) [ Time Frame: up to Day 8 ] [ Designated as safety issue: No ]
  • Exploration of mutations that emerge with exposure to BILR 355 BS to determine the effect on both viral load and IC50 fold change from reference [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 12 hours post-dose (AUC0-12h) [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: up to week 5 ] [ Designated as safety issue: No ]
  • Changes in total cholesterol, LDL, HDL and triglycerides from baseline to days 8 and 35 [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of rash, hepatic events, and CNS adverse events [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of any adverse events (treatment related and unrelated) [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of laboratory test abnormalities [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of serious adverse events (including AIDS-defining events) [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of ≥ DAIDS 2 Grade elevation in ALT/AST [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]
  • Incidence of AEs leading to discontinuation from the study [ Time Frame: up to week 9 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: February 2006
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/?l.

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00294372

Locations
Germany
Boehringer Ingelheim Investigational Site
Berlin, Germany
Boehringer Ingelheim Investigational Site
Bochum, Germany
Boehringer Ingelheim Investigational Site
Bonn, Germany
Boehringer Ingelheim Investigational Site
Erlangen, Germany
Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
Boehringer Ingelheim Investigational Site
Hamburg, Germany
Boehringer Ingelheim Investigational Site
Hannover, Germany
Boehringer Ingelheim Investigational Site
Heidelberg, Germany
Boehringer Ingelheim Investigational Site
Mainz, Germany
Boehringer Ingelheim Investigational Site
Munchen, Germany
Boehringer Ingelheim Investigational Site
Ulm, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00294372     History of Changes
Other Study ID Numbers: 1188.31
Study First Received: February 20, 2006
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014