PMPA Trials Recruiting: Atlanta, (Baltimore), Berkeley, Birmingham, Brookline, Chicago, Cleveland, Dallas, Denver, Hershe
A phase II trial of an oral prodrug of PMPA, an experimental antiretroviral, began enrolling September 4 and is seeking 175 patients at research sites in 20 U.S. cities. And a separate phase I/II study of oral PMPA plus hydroxyurea is enrolling in three cities: Baltimore, San Francisco, and Seattle. Both trials are being conducted by Gilead Sciences, headquartered in Foster City, California. (Baltimore and Seattle are listed in parentheses above because only the combination trial is located there; San Francisco has both (its combination study with hydroxyurea is currently full, although more volunteers may be sought later.)The larger trial (not involving hydroxyurea) is seeking volunteers who have a viral load between 400 and 50,000 copies, and who have been on a stable antiviral regimen for at least eight weeks; there is no CD4 count requirement. Volunteers will be randomly assigned to receive one of three doses of PMPA, or a placebo, in addition to maintaining their ongoing regimen. The trial will last 48 weeks, and after 24 weeks, those who had been assigned to placebo will be eligible to switch to the active drug. The oral form of PMPA, which is used in this trial, is usually taken once per day.
The smaller trial of the combination of PMPA plus hydroxyurea requires a viral load of at least 10,000 copies, and a CD4 count of at least 200. Hydroxyurea has been shown to enhance the activity of PMPA in laboratory studies.
Comment
PMPA is currently one of the more promising experimental anti-HIV drugs in the pipeline. It is chemically related to PMEA, which is the active form of adefovir dipivoxil (PREVEON (tm)), which is currently available on expanded access. But laboratory, animal, and human studies of up to 28 days of dosing have suggested that PMPA may be the more effective drug--if it is found to be safe when used for a long time. (A full report on the 28-day human study is appearing now in Antimicrobial Agents and Chemotherapy; we have not seen that article before going to press. An earlier account of the results was presented at the Retroviruses conference in February of this year.)
A caution about the PMPA trial is that the related drug adefovir can cause kidney toxicity in long-term use. PMPA might or might not be similar; if it is, this toxicity could develop after several months, and would not have been seen in the 28-day trial. Therefore it is important that volunteers be monitored carefully, and not discount any required safety tests as merely routine.
Note: Both PMEA and PMPA are not used directly, as they would have to be given by injection. Instead, for each of them a once-a-day "prodrug" has been prepared; these are related compounds which are taken orally and are chemically changed into PMEA or PMPA by the body. These oral drugs are bis-pom PMEA (also called adefovir dipivoxil, or PREVEON), and bis-poc PMPA (which is being used in the trials described here).
For More Information
For more information about either the 20-city PMPA trial, or the 3-city PMPA-plus-hydroxyurea trial, call either the AIDS Clinical Trials Information Service, 800-TRIALS-A, or Gilead Sciences Medical Information, 800-GILEAD-5. Both organizations should soon be ready to provide information about these trials, or refer callers to a site in one of the cities listed above.
