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

13 november 2013 bijgewerkt door: Boehringer Ingelheim

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

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

Studie Overzicht

Toestand

Beëindigd

Conditie

HIV-infecties

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving

Fase

Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

Duitsland
- - Berlin, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Bochum, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Bonn, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Erlangen, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Frankfurt/Main, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Hamburg, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Hannover, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Heidelberg, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Mainz, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Munchen, Duitsland
    - Boehringer Ingelheim Investigational Site
  - Ulm, Duitsland
    - Boehringer Ingelheim Investigational Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation.
HIV-1 infected males or females >= 18 years of age.
History of NNRTI based HAART >= 8 weeks and at least one, but not more than 3 NNRTI-associated resistance mutations by current genotype
TPV/r or LPV/r susceptible
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:

The following resistance mutations demonstrated at any time prior to starting trial therapy: V106A and/or Y188L
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.
Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT > DAIDS Grade 1
Acute/previous mycobacterial or invasive fungal infection requiring therapy or prophylaxis with drugs interfering with or significantly affected by the cytochrome P450 system
Use of investigational medications within 30 days before study entry or during the trial.
Use of concomitant drugs that may significantly reduce plasma levels of the study medications.
Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
Patients currently treated with systemic ant-cancer chemotherapy
Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator.
In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Primair doel: Behandeling
Toewijzing: Gerandomiseerd
Interventioneel model: Parallelle opdracht
Masker: Dubbele

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat	Tijdsspanne
The primary endpoint will be reduction in plasma HIV-1 RNA from baseline to day 8, expressed in log10 copies/mm3. Tijdsspanne: day 8	day 8

Secundaire uitkomstmaten

Uitkomstmaat	Tijdsspanne
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 Tijdsspanne: up to week 5	up to week 5
Change from baseline in viral load at each visit Tijdsspanne: up to week 9	up to week 9
Change from baseline in CD4+ cell counts at each visit Tijdsspanne: up to week 9	up to week 9
Time averaged change from baseline in viral load through Days 8 and 35 Tijdsspanne: up to week 5	up to week 5
Number of reverse transcriptase (RT) mutations at baseline Tijdsspanne: up to week 5	up to week 5
Number of NNRTI resistance-associated mutations at baseline (refer to Appendix 10.4) Tijdsspanne: up to week 5	up to week 5
The presence of specific RT mutations (both in the list of NNRTI mutations and not in the list for exploratory purposes) at baseline Tijdsspanne: up to week 5	up to week 5
The inhibitory quotient and minimum measured concentration of the analyte in plasma (Cmin) Tijdsspanne: up to Day 8	up to Day 8
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 Tijdsspanne: up to week 5	up to week 5
Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 12 hours post-dose (AUC0-12h) Tijdsspanne: up to week 5	up to week 5
Maximum measured concentration of the analyte in plasma (Cmax) Tijdsspanne: up to week 5	up to week 5
Changes in total cholesterol, LDL, HDL and triglycerides from baseline to days 8 and 35 Tijdsspanne: up to week 9	up to week 9
Incidence of rash, hepatic events, and CNS adverse events Tijdsspanne: up to week 9	up to week 9
Incidence of any adverse events (treatment related and unrelated) Tijdsspanne: up to week 9	up to week 9
Incidence of laboratory test abnormalities Tijdsspanne: up to week 9	up to week 9
Incidence of serious adverse events (including AIDS-defining events) Tijdsspanne: up to week 9	up to week 9
Incidence of ≥ DAIDS 2 Grade elevation in ALT/AST Tijdsspanne: up to week 9	up to week 9
Incidence of AEs leading to discontinuation from the study Tijdsspanne: up to week 9	up to week 9

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Boehringer Ingelheim

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 februari 2006

Primaire voltooiing (Werkelijk)

1 september 2007

Studieregistratiedata

Eerst ingediend

20 februari 2006

Eerst ingediend dat voldeed aan de QC-criteria