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

NCT ID: NCT00063804

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2006-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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HIV Seronegativity CXCR4 AMD11070

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

escalating single doses of AMD070 ranging from 1/4 to 1 times the maximum tolerated dose (MTD)

Group Type EXPERIMENTAL

AMD070

Intervention Type DRUG

2

single dose of 200 mg AMD070 after eating a standardized meal

Group Type EXPERIMENTAL

AMD070

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Ritonavir

Intervention Type DRUG

AMD070

Intervention Type DRUG

Interventions

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Ritonavir

Intervention Type DRUG

AMD070

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Craig Hendrix, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 15183346 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16091227 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16005254 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 15134547 (View on PubMed)

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.

Reference Type RESULT
PMID: 17452489 (View on PubMed)

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.

Reference Type RESULT
PMID: 18285477 (View on PubMed)

Other Identifiers

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10012

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5191

Identifier Type: -

Identifier Source: secondary_id

A5191

Identifier Type: -

Identifier Source: org_study_id