HIV InfectionsPhase 1NCT00063804
Safety of AMD070 When Administered Alone or Boosted With Low-Dose Ritonavir in HIV Uninfected Men
A Phase 1 study testing Ritonavir and AMD070 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Ritonavir and AMD070
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 2 sitesUnited States
- Study dates
- Start not givento Oct 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21205
University of Washington AIDS CRS
Seattle, Washington, 98104
About this 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
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- Ritonavir, AMD070
- Keywords
- HIV Seronegativity, CXCR4, AMD11070
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitonavirDrug
AMD070Drug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | escalating single doses of AMD070 ranging from 1/4 to 1 times the maximum tolerated dose (MTD) Receives: Drug: AMD070 |
| 2 | Experimental | single dose of 200 mg AMD070 after eating a standardized meal Receives: 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 Receives: Drug: Ritonavir; Drug: AMD070 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2003 (estimated)
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Craig Hendrix, MD, Study chair, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00063804
- Sponsor's protocol ID
- A5191
- Other IDs
- 10012, ACTG A5191
- Status last verified
- Oct 2021
- First submitted
- 7 Jul 2003
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
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.
PubMed 15183346Marks 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.
PubMed 16091227Princen 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.
PubMed 16005254Schols D. HIV co-receptors as targets for antiviral therapy. Curr Top Med Chem. 2004;4(9):883-93. doi: 10.2174/1568026043388501.
PubMed 15134547Stone 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.
PubMed 17452489Cao 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.
PubMed 18285477
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00063804
- Acronym / sponsor ID
- A5191
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, CXCR4, AMD11070
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study completion
- Oct 2006 (actual)
- First posted
- 8 Jul 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AMD070escalating single doses of AMD070 ranging from 1/4 to 1 times the maximum tolerated dose (MTD) |
| 2 | Experimental | Drug: AMD070single dose of 200 mg AMD070 after eating a standardized meal |
| 3 | Experimental | Drug: Ritonavir, Drug: AMD070single dose of 200 mg AMD070 on Days 1, 3, and 17 and single dose of 100 mg ritonavir on Days 3 through 18 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ritonavir | Drug | 3 |
| AMD070 | Drug | 1, 2, 3 |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 15183346De 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.
- Background: PubMed 16091227Marks 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.
- Background: PubMed 16005254Princen 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.
- Background: PubMed 15134547Schols D. HIV co-receptors as targets for antiviral therapy. Curr Top Med Chem. 2004;4(9):883-93. doi: 10.2174/1568026043388501.
- Results publication: PubMed 17452489Stone 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.
- Results publication: PubMed 18285477Cao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Hendrix, MD study chair
Johns Hopkins University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ritonavir and AMD070 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AMD070 pharmacokinetic (PK) parameters under three conditions, and the within-volunteer differences between them. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00063804, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.