Important to the development of any treatment for scleroderma is a clinical study investigating the pharmacodynamics and pharmacokinetics of a potential drug candidate. NexMed (USA), Inc., a subsidiary of Apricus Biosciences, Inc., is sponsoring a currently enrolling clinical trial investigating these two aspects of alprostadil in systemic sclerosis (SSc) patients with a secondary diagnosis of Raynaud’s phenomenon, also known as scleroderma-related Raynaud’s phenomenon.
In contrast to the more common format of two groups of patients receiving only either a drug or a placebo, “Study of Acute Peripheral Vascular Effects, Pharmacokinetics, Safety and Tolerability in Subjects With Raynaud’s Phenomenon Secondary to Systemic Sclerosis” follows the crossover assignment intervention model. During the phase 2 trial, enrolled patients will be split into three experimental groups, each using alprostadil topical cream and a placebo during the treatment period at separate times. The three different groups will test three different doses of alprostadil (or placebo) cream: 300 micrograms, 1 milligram, or 3 milligrams.
One evaluation period lasts for four hours. After applying the cream and undergoing a cold challenge, patients will be evaluated by laser Doppler capillary velocimetry for blood perfusion in their fingers, as well as by thermography for temperature recovery in their fingers. In addition to these pharamcodynamic metrics, pharmacokinetics will be evaluated after application use blood sampling to determine maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration time curve, and time to eliminate from the body half the applied dose.
Throughout time, patients will be monitored to determine the safety of treatment based on adverse events, vital signs, electrocardiograms, and physical examinations. Before a treatment session, patients must follow a few inclusion criteria in order to ensure there are no confounding variables to affect results.
Alprostadil, also known by its common scientific name prostaglandin E1, has been studied to manage Raynaud’s phenomenon due to SSc since before 1999. An international group of researchers at the University of Messina in Italy treated six females with a three-hour infusion of alprostadil for six consecutive days and another six females with an infusion of placebo. “After infusion, blood flow, digitally measured by telethermography was increased only in patients treated with alprostadil,” wrote the authors in their journal article, “Efficacy Evaluation of Prostaglandin E1 against Placebo in Patients with Progressive Systemic Sclerosis and Significant Raynaud’s Phenomenon.” The current trial may be more patient-friendly, as treatment consists of a topical cream rather than an infusion.