Open-label titration study of the safety of RMP-7 in patients with the acquired immune deficiency syndrome

Area of Science:

• Pharmacology
• Neuroscience
• Immunology

Background:

• RMP-7, a bradykinin analogue, enhances blood-brain barrier permeability in animal models.
• This effect allows increased delivery of small molecules, like amphotericin B, across the blood-brain barrier.
• The safety of RMP-7 in human immunodeficiency virus (HIV)-infected individuals with acquired immune deficiency syndrome (AIDS) was previously unevaluated.

Purpose of the Study:

• To assess the safety and tolerability of escalating doses of RMP-7 in adults with AIDS.
• To evaluate dose-related adverse events associated with RMP-7 administration in this vulnerable population.

Main Methods:

• Six HIV-positive adults with CD4+ cell counts below 50/mm3 received escalating doses of RMP-7 (30, 100, and 300 ng/kg) intravenously over successive days.
• Adverse experiences, vital signs (pulse rate, mean arterial pressure), and liver enzymes were monitored.
• Safety was evaluated based on the incidence and severity of adverse events.

Main Results:

• Adverse experiences were dose-dependent, mild to moderate, and primarily consisted of vasodilation-related effects.
• Transient increases in pulse rate and minor, temporary changes in mean arterial pressure were observed.
• Three patients with pre-existing liver enzyme elevations showed minor increases, with no new elevations in others.

Conclusions:

• RMP-7 was found to be safe and well-tolerated in AIDS patients at all tested doses.
• Adverse effects were consistent with those observed in healthy volunteers, despite pre-existing cardiovascular risks in this population.
• RMP-7 demonstrates potential for enhancing drug delivery across the blood-brain barrier in HIV-infected individuals.