Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection

This study has been terminated.
(Sponsor decision)
Sponsor:
Information provided by (Responsible Party):
Avexa
ClinicalTrials.gov Identifier:
NCT00612898
First received: January 30, 2008
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

Apricitabine is a new NRTI which is active against drug-resistant HIV. NRTIs are often included as part of patients' treatment, but many HIV-infected patients develop resistance to commonly used NRTIs such as lamivudine (3TC) and emtricitabine (FTC). This study will examine whether including apricitabine as part of patients' treatment is more effective than including lamivudine,when patients change treatment because of drug resistance.


Condition Intervention Phase
HIV Infections
Drug: apricitabine
Drug: lamivudine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase

Resource links provided by NLM:


Further study details as provided by Avexa:

Primary Outcome Measures:
  • Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to loss of virological response (TLOVR analysis; FDA algorithm) at W12, W24 and W48 (<50 copies/mL) [ Time Frame: week 12, 24, and 48 ] [ Designated as safety issue: No ]
  • Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W48 [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Enrollment: 239
Study Start Date: February 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
800mg BID apricitabine plus optimised background
Drug: apricitabine
800mg BID apricitabine orally for 48 weeks
Other Name: AVX754
Active Comparator: 2
150mg BID lamivudine plus optimised background
Drug: lamivudine
150mg BID lamivudine orally for 48 weeks
Other Name: 3TC

Detailed Description:

ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase.

The M184V mutation is most commonly present amongst patients failing regimens containing either of the two deoxycytidine analogs lamivudine and emtricitabine. Whilst lamivudine therapy is often maintained in patients harboring the M184V mutation in some settings, there are no deoxycytidine analogs currently available that effectively suppress replication of HIV-1 containing the M184V/I mutation, particularly in the presence of other additional NRTI mutations.

The purpose of this study is to extend the efficacy and safety established in study AVX-201 of ATC in patients who are HIV-1 infected and have failed treatment with lamivudine or emtricitabine and have confirmed M184V/I mutation. Patients to be enrolled will be failing their current lamivudine- or emtricitabine-containing regimen and therefore have limited remaining NRTI treatment options. This study will investigate whether it is possible to improve control of HIV-1 viral replication by including ATC within a treatment experienced patient's new optimized background regimen following ART treatment failure.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 positive with M184V/I mutation in reverse transcriptase;
  • 18 years of age or older;
  • Currently taking lamivudine (3TC) or emtricitabine (FTC)

Exclusion Criteria:

  • Female patients who are pregnant or breastfeeding;
  • Current hepatitis B virus (HBV) infection;
  • Current treatment for hepatitis C virus infection;
  • Renal function not adequate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00612898

  Show 100 Study Locations
Sponsors and Collaborators
Avexa
Investigators
Study Director: Susan W Cox, Ph D Avexa Ltd
Principal Investigator: Michael Saag, MD UAB Center for AIDS Research
  More Information

No publications provided

Responsible Party: Avexa
ClinicalTrials.gov Identifier: NCT00612898     History of Changes
Other Study ID Numbers: AVX-301
Study First Received: January 30, 2008
Last Updated: January 19, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Human Research Bioethics Committee
Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Portugal: Ethics Committee for Clinical Research
South Africa: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency
Israel: Ministry of Health
Canada: Health Canada
Guatemala: Health ministry
India: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Thailand: Food and Drug Administration
Peru: Ministry of Health
Mexico: Ministry of Health
Uganda: Ministry of Health

Keywords provided by Avexa:
HIV infection
Drug resistance
Reverse transcriptase inhibitor
Nucleoside analogue
treatment experienced

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
Lamivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 15, 2014