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

NCT00063804 | Completed Phase 1

• 3 other identifiers: A519110012ACTG A5191
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV Seronegativity; CXCR4; AMD11070

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

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

Interventions

Ritonavir DRUG

3

AMD070 DRUG

1; 2; 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (2)

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21205, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Related Publications (6)

• De Clercq E. HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches. Int J Biochem Cell Biol. 2004 Sep;36(9):1800-22. doi: 10.1016/j.biocel.2004.02.015.

  PMID: 15183346 BACKGROUND

• Marks K, Gulick RM. New antiretroviral agents for the treatment of HIV infection. Curr HIV/AIDS Rep. 2004 Jun;1(2):82-8. doi: 10.1007/s11904-004-0012-0.

  PMID: 16091227 BACKGROUND

• Princen K, Schols D. HIV chemokine receptor inhibitors as novel anti-HIV drugs. Cytokine Growth Factor Rev. 2005 Dec;16(6):659-77. doi: 10.1016/j.cytogfr.2005.05.009. Epub 2005 Jul 6.

  PMID: 16005254 BACKGROUND

• Schols D. HIV co-receptors as targets for antiviral therapy. Curr Top Med Chem. 2004;4(9):883-93. doi: 10.2174/1568026043388501.

  PMID: 15134547 BACKGROUND

• Stone ND, Dunaway SB, Flexner C, 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. Antimicrob Agents Chemother. 2007 Jul;51(7):2351-8. doi: 10.1128/AAC.00013-07. Epub 2007 Apr 23.

  PMID: 17452489 RESULT

• Cao YJ, Flexner CW, Dunaway S, Park JG, Klingman K, Wiggins I, Conley J, Radebaugh C, Kashuba AD, MacFarland R, Becker S, Hendrix CW. Effect of low-dose ritonavir on the pharmacokinetics of the CXCR4 antagonist AMD070 in healthy volunteers. Antimicrob Agents Chemother. 2008 May;52(5):1630-4. doi: 10.1128/AAC.01460-07. Epub 2008 Feb 19.

  PMID: 18285477 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; mavorixafor

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Craig Hendrix, MD

  Johns Hopkins University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2003
• First Posted: July 8, 2003
• Study Completion: October 1, 2006
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (2)