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

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00063804
First received: July 7, 2003
Last updated: May 17, 2012
Last verified: May 2012
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Enrollment: 44
Study Completion Date: October 2006
Arms Assigned Interventions
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
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
AIDS Clinical Trials Group
Investigators
Study Chair: Craig Hendrix, MD Johns Hopkins University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00063804     History of Changes
Other Study ID Numbers: A5191, 10012, ACTG A5191
Study First Received: July 7, 2003
Last Updated: May 17, 2012
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014