Phase IB/IIA Dose-Finding Safety and Activity Study of AMD11070 (An Orally Administered CXCR4 Entry Inhibitor) in HIV-Infected Subjects
AMD11070
Blood-Borne Infections+11
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
Study start date: November 1, 2004
Actual date on which the first participant was enrolled.AMD11070 is an oral HIV-1 entry inhibitor that targets the CXCR4 receptor on T cells. AMD11070 has been shown safe and well-tolerated in Phase I clinical trials in HIV uninfected people. The goal of this study is to evaluate the safety and antiretroviral activity of eight dose levels of AMD11070 in HIV infected adults with X4-tropic virus. Pharmacokinetics (PK) of AMD11070 will also be studied. This study will last 90 days. All participants will receive medication for 10 days. There are eight cohorts in this study, with a maximum of six participants per cohort. Cohort A will receive 200 mg AMD11070 every 12 hours; Cohort B will receive 400 mg AMD11070 every 12 hours; Cohort C will receive 600 mg AMD11070 every 12 hours; Cohort D will receive 800 mg AMD11070 every 12 hours; Cohort E will receive 1000 mg AMD11070 daily; Cohort F will receive 1500 mg AMD11070 daily; Cohort G will receive 1000 mg AMD11070 every 12 hours; and Cohort H will receive 2000 mg AMD11070 daily. Cohorts B, C, D, and E will open sequentially, provided no more than one of six participants in the preceding cohort experiences dose-limiting toxicity (DLT) based on safety evaluations through Day 17. Cohort G will open to enrollment when Cohort E is filled; Cohort H will open to enrollment when Cohort F is filled. Cohort F will open to enrollment provided no more than one of six participants of Cohorts E and G experiences DLT. All study participants will be offered to receive open-label AMD11070 through a separate long-term safety study. Participants will either be admitted to the general clinical research center (GCRC) for the dosing period or have dosing, PK testing, and other study monitoring done on an outpatient basis, depending on the study site. Participants admitted to the GCRC for the dosing period will be allowed daytime passes from the GCRC on Days 4, 6, 7, 8, and 9. During the study, participants will have continuous heart monitoring, serial electrocardiograms (EKGs), and vital sign checks. Fasting blood collection will occur on Days 5 and 10. Trough PK testing will occur at entry and on Days 1, 2, 3, 4, 6, 8, and 11. Intensive 24-hour PK testing and 24-hour urine collection will occur on Days 10 and 11. After treatment, targeted physicals and urine collection will occur on Days 17, 30, and 90, and additional blood collection will occur on Days 17, 21, 30, and 90. Participants will undergo an EKG on Days 17 and 90. Participants will also undergo an opthalmologic evaluation and questionnaire sometime after receiving AMD11070.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.6 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * HIV-1 infected * Have X4- or dual/mixed-tropic virus confirmed no more than 56 days prior to study entry * HIV-1 viral load of 5,000 copies/ml or more within 60 days prior to study entry * If female, willing to discontinue hormonal contraception 1 week prior to study entry * Willing to use acceptable forms of contraception Exclusion Criteria: * Antiretroviral treatment within 14 days prior to study entry * Other prescription medications, herbal supplements, or aspirin within 7 days prior to study entry. Patients taking medication for prophylaxis for Pneumocystis carinii pneumonia (PCP) are not excluded. Patients taking medications approved by protocol officials are not excluded, provided they have been on a stable dose for at least 14 days prior to study entry. * Nonsteroidal anti-inflammatory drugs (NSAIDS), over the counter medications, or other supplements (including multivitamins) within 1 day prior to study entry * Heavy exercise within 24 hours before study entry evaluations are done * Immunizations within 30 days prior to study entry * Radiation therapy, cytotoxic chemotherapeutic agents, or immunomodulatory agents within 30 days prior to study entry * Current use of some CYP substrates, inhibitors, or inducers. Use of CYP450 substrates is allowed, except for CYP2D6 and CYP2C8 substrates. * Current use of P-gp inducers or inhibitors * Allergy or sensitivity to study drug or its formulations * Active infection or acute illness within 14 days prior to study entry, including HIV-associated opportunistic infections * History of heart abnormalities. Patients with any repolarization delay (QTc interval of greater than 500 msec) or a history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia) are also excluded. * Drug or alcohol abuse or dependence or other medical or psychological condition that, in the opinion of the investigator, would interfere with the study or put participants at undue risk * Chronic diarrhea, defined as having more than 3 stools/day for more than 4 weeks prior to study entry * Pregnant or breastfeeding
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.8 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalGroup III
ExperimentalGroup IV
ExperimentalGroup 5
ExperimentalGroup 6
ExperimentalGroup 7
ExperimentalGroup 8
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 3 locations
The Ponce de Leon Ctr. CRS
Atlanta, United StatesIndiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, United States