Safety of AMD070 When Administered Alone or Boosted With Low-Dose Ritonavir in HIV Uninfected Men - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00063804

Purpose

Most currently approved anti-HIV drugs work by stopping the replication of HIV after it has entered cells. AMD070 (also known as AMD11070) is designed to block HIV from entering cells and may be effective in treating patients who have developed resistance to or are unable to take other anti-HIV drugs. This study will evaluate the safety of different doses of AMD070 along with AMD070 boosted with ritonavir (RTV) in HIV uninfected men.

Condition	Intervention	Phase
HIV Infections	Drug: Ritonavir Drug: AMD070	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Parallel Assignment, Pharmacokinetics Study
Official Title:	A Phase 1, Dose-Rising Study of AMD11070 in HIV-Seronegative Men to Assess the Safety and Pharmacokinetics After Single or Multiple Doses

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir AMD 070

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

AMD070 pharmacokinetic (PK) parameters under three conditions, and the within-volunteer differences between them
Steady-state RTV PK parameters
Grade 3 and 4 adverse effects, as defined by the protocol

Estimated Enrollment:

39

Arms	Assigned Interventions
1: Experimental escalating single doses of AMD070 ranging from 1/4 to 1 times the maximum tolerated dose (MTD)	Drug: AMD070
2: Experimental single dose of 200 mg AMD070 after eating a standardized meal	Drug: AMD070
3: Experimental single dose of 200 mg AMD070 on Days 1, 3, and 17 and single dose of 100 mg ritonavir on Days 3 through 18	Drug: Ritonavir Drug: AMD070

Detailed Description:

Current therapy for HIV infection primarily uses drugs that inhibit HIV replication via inhibition of viral protease and reverse transcriptase. Many patients either do not tolerate these medications well or develop virologic failure due to incomplete viral suppression and development of antiviral resistance. New drugs target HIV entry into the cell. AMD070 binds to the chemokine receptor CXCR4, inhibiting membrane fusion and viral entry. Animal studies have shown AMD070 to be generally safe and well tolerated. The dose-escalation and drug-drug interaction study will evaluate the safety, tolerability, and pharmacokinetics of single, multiple, and RTV-boosted doses of AMD070 in healthy, HIV uninfected male volunteers.

Participants in this study will be assigned to a single- or multiple-dose AMD070 group (Group 1), a single-dose AMD070 group (Group 2), or an RTV-boosted, multiple-dose AMD070 group (Group 3). Some participants in Group 1 will be given AMD070 once on an empty stomach with no food or drink except for water for 2 hours before and 1 hour after receiving the drug. Up to 4 different doses will be tested in subgroups of Group 1 participants. Some participants in Group 1 will be given AMD070 7 times, 12 hours apart, after eating a standardized breakfast 30 minutes before receiving the drug; 3 different doses will be tested in this group. Participants in Group 2 will be given a single dose of AMD070 after eating a standardized meal. Participants in Group 3 will be given a morning dose of AMD070 on Days 1, 3, and 17 after eating a standardized breakfast 30 minutes before receiving the drug, and a morning and evening dose of RTV on Days 3 through 18. Group 3 participants may also be asked to enroll in an additional study group that will receive a single dose of AMD070 on Days 1 and 3 while fasting.

All participants will be observed as hospital inpatients. Group 1 and 2 participants will stay in the hospital for 24 hours; Group 3 participants will stay in the hospital for 4 days. All participants will have blood and urine collection throughout their hospital stay. Group 3 participants selected to join in the additional study group will have blood and urine samples collected throughout the 5-day study. These participants will be discharged from the hospital on Day 5 and have a follow-up visit around Day 35. All study participants will also undergo an ophthalmologic evaluation and questionnaire sometime after receiving AMD070.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria for all participants:

HIV uninfected males in good general health
Normal electrocardiogram (EKG) and lab values
Body weight within 33% of ideal weight for height within 28 days of study entry
Willing to refrain from exercise for 24 hours prior to study entry
Willing to use acceptable forms of contraception

Inclusion Criteria for Group 3's Additional Study:

Willing to refrain from consumption of alcohol and grapefruit juice for the duration of the study

Exclusion Criteria for all participants:

Prescription medications, herbal supplements, or aspirin within 7 days of study entry
Nonsteroidal anti-inflammatory drugs, over-the-counter medications, and other supplements (including multivitamins) within 1 day of study entry
Active infection or acute illness within 14 days of study entry
Drug or alcohol abuse or dependence
Known sensitivity to AMD070
History of gastrointestinal bleeding or ulcer
Any medical or psychological condition that, in the opinion of the investigator, would interfere with study participation

Exclusion Criteria for Group 3:

Immunizations within 30 days of study entry
Radiation therapy, cytotoxic chemotherapeutic agents, or immunomodulating agents within 30 days of study entry
Chronic diarrhea for more than 4 weeks prior to study entry
Heart conduction abnormalities, heart arrhythmias, cardiomyopathy, any repolarization delay, or other risk factors for heart failure and hypokalemia

Exclusion Criteria for Group 3's Additional Study:

Grade 3 or 4 adverse event while participating in Group 3
Consumption of alcohol within 48 hours of study entry

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063804

Locations

United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Washington
University of Washington (Seattle)
Seattle, Washington, United States, 98104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:

Craig Hendrix, MD

Johns Hopkins University

More Information

Additional Information:

Click here for more information about AMD070. This link exits the ClinicalTrials.gov site

Click here for more information about ritonavir. This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Stone ND, Dunaway SB, Flexner CW, Tierney C, Calandra GB, Becker S, Cao YJ, Wiggins IP, Conley J, Macfarland RT, Park JG, Lalama C, Snyder S, Kallungal B, Klingman KL, Hendrix CW. Multiple Dose Escalation Study of the Safety, Pharmacokinetics, and Biologic Activity of Oral AMD070, a selective CXCR4 Receptor Inhibitor, in Human Subjects (ACTG A5191). Antimicrob Agents Chemother. 2007 Apr 23; [Epub ahead of print]

De Clercq E. HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches. Int J Biochem Cell Biol. 2004 Sep;36(9):1800-22. Review.

Marks K, Gulick RM. New antiretroviral agents for the treatment of HIV infection. Curr HIV/AIDS Rep. 2004 Jun;1(2):82-8. Review.

Princen K, Schols D. HIV chemokine receptor inhibitors as novel anti-HIV drugs. Cytokine Growth Factor Rev. 2005 Dec;16(6):659-77. Epub 2005 Jul 6. Review.

Schols D. HIV co-receptors as targets for antiviral therapy. Curr Top Med Chem. 2004;4(9):883-93. Review.

Study ID Numbers:	ACTG A5191
Study First Received:	July 7, 2003
Last Updated:	July 28, 2008
ClinicalTrials.gov Identifier:	NCT00063804 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV Seronegativity
CXCR4
AMD11070

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Ritonavir
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on November 09, 2009