A Safety and Efficacy Study of Amdoxovir in HIV-1 Treatment-experienced Subjects. - Full Text View

Purpose

This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily.

The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.

Condition	Intervention	Phase
Human Immunodeficiency Virus Infection	Drug: amdoxovir 300 mg bid Drug: amdoxovir 500 mg bid Drug: tenofovir DF 300 mg qd	Phase 2

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 IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Tenofovir Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by RFS Pharma, LLC:

Primary Outcome Measures:

HIV-1 viral load [ Time Frame: change from baseline to Week 2 ] [ Designated as safety issue: No ]
Safety and Tolerability- Incidence of adverse events and laboratory abnormalities [ Time Frame: number and frequency from baseline through Week 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

HIV-1 viral load [ Time Frame: change from baseline to Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]
Changes in Immunologic Function (CD4 cell counts) [ Time Frame: changes from baseline to Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	December 2012
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: amdoxovir 300 mg bid in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3	Drug: amdoxovir 300 mg bid 2 x 150 mg capsules bid Other Names: DAPD AMDX
Experimental: amdoxovir 500 mg bid in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3	Drug: amdoxovir 500 mg bid 2 x 250 mg capsules bid Other Names: DAPD AMDX
Active Comparator: tenofovir DF 300 mg qd in combination with zidovudine 300 mg bid for 12 weeks; lopinavir/ritonavir (400 mg/100 mg) bid is added on week 3	Drug: tenofovir DF 300 mg qd 1 x 300 mg tablet once daily Other Name: Viread

Eligibility

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

Criteria

Inclusion Criteria:

Male or female ≥ 18 years old with HIV-1 RNA ≥ 2,000 copies/mL and currently failing therapy.
Has M184I/V mutation in addition to 0-2 thymidine analog mutations (TAMs) at screening.
Agree to be abstinent or use two reliable forms of contraception (for females) and one form for men when participating in sexual activity that could result in pregnancy.

Exclusion Criteria:

Current or recent (last 30 days of study entry) AIDS defining diseases.
Genotypic resistance testing at screening indicating K65R, L74V, Q151M mutation.
Prior exposure to lopinavir/ritonavir or amdoxovir.
Impaired hepatic function (ALT > 5 x ULN).
Women who are pregnant or breast feeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737359

Locations

Argentina
Research Site
Rosario, Santa Fe, Argentina, S2000CXP
Research Site
Rosario, Santa Fe, Argentina, S2000PBJ
Research Site
Buenos Aires, Argentina, C1426EGR
Research Site
Buenos Aires, Argentina, C1202ABB
Research Site
Buenos Aires, Argentina, C1141ACG
Research Site
Buenos Aires, Argentina, C1405CKC

Sponsors and Collaborators

RFS Pharma, LLC

Investigators

Study Director:

Luz Pascual, MD MPH

RFS Pharma

More Information

No publications provided

Responsible Party:	RFS Pharma, LLC
ClinicalTrials.gov Identifier:	NCT01737359 History of Changes
Other Study ID Numbers:	RFSP-AMDX-2010
Study First Received:	November 27, 2012
Last Updated:	March 27, 2013
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by RFS Pharma, LLC:

amdoxovir
zidovudine
tenofovir DF

HIV
HAART
antiretroviral

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Virus Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Zidovudine
Tenofovir

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

ClinicalTrials.gov processed this record on June 18, 2013