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

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ClinicalTrials.gov Identifier: NCT00063804
Recruitment Status : Completed
First Posted : July 8, 2003
Last Update Posted : May 21, 2012
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Ritonavir Drug: AMD070 Phase 1

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Completion Date : October 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Ritonavir
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
escalating single doses of AMD070 ranging from 1/4 to 1 times the maximum tolerated dose (MTD)
Drug: AMD070
Experimental: 2
single dose of 200 mg AMD070 after eating a standardized meal
Drug: AMD070
Experimental: 3
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

Outcome Measures

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00063804

United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21205
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
AIDS Clinical Trials Group
Study Chair: Craig Hendrix, MD Johns Hopkins University
More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00063804     History of Changes
Other Study ID Numbers: A5191
10012 ( Registry Identifier: DAIDS ES )
ACTG A5191
First Posted: July 8, 2003    Key Record Dates
Last Update Posted: May 21, 2012
Last Verified: May 2012

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

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors