Guilford Pharmaceuticals Inc has initiated a Phase II clinical trial of its novel neuroimmunophilin ligand, GPI 1485, for the treatment of Parkinson's disease.
"This Phase II trial will provide a rigorous assessment of the long-term treatment effect of GPI 1485 in patients with mild to moderate Parkinson's disease," commented Craig R. Smith, Chairman and Chief Executive Officer. "We've designed the trial to evaluate the findings from the first Phase II study completed last year. In particular, the current Phase II trial will look more thoroughly at the ability of GPI 1485 to reduce the requirement for conventional symptomatic therapy, which often is associated with debilitating side effects, as well as further assess the imaging results that indicate GPI 1485 may reduce the rate of progression of this disabling disease."
The Phase II clinical trial is a multicenter, randomized, double-blind, placebo-controlled evaluation of the safety, pharmacokinetics and efficacy of GPI 1485 in patients with mild to moderate Parkinson's disease. A total of 200 patients over the age of 55 years will be enrolled and randomly assigned to receive either placebo or GPI 1485 orally four times a day. To be eligible for the study, patients have to be optimally treated and have stable symptoms of Parkinson's disease.
The primary endpoint in the study is a 50% or greater reduction in the loss of dopamine transporters as measured by I-123 Beta CIT SPECT imaging. The clinical endpoints will be time to initiation of L-Dopa therapy, as well as other measures of clinical improvement and safety, including changes from baseline in the UPDRS global rating scale and motor subscale, and changes from baseline in cognitive function, sleep, mood, and quality of life measures. Patients are eligible to be enrolled in the trial if they are receiving dopamine agonists, but not L-Dopa. All medications administered during the trial will be converted to L-Dopa equivalents, allowing comparative measures of drug sparing.
In April 2002, Guilford Pharmaceuticals announced results from a Phase II clinical trial completed by Amgen in 2001. The data from this trial suggested that oral administration of GPI 1485 may retard the loss of dopamine transporters, a marker of disease progression in patients with Parkinson's disease.
GPI 1485 was well tolerated but did not produce a substantial reversal of the motor symptoms of Parkinson's disease after six months of treatment. GPI 1485 is an investigational new drug that belongs to a class of compounds called neuroimmunophilin ligands. Neuroimmunophilin ligands are small molecules that in preclinical experiments have been shown to be orally bioavailable, cross the blood-brain barrier, and repair and regenerate damaged nerve terminals without affecting normal nerves. In addition to Parkinson's disease, neuroimmunophilin ligands may have application in the treatment of a broad range of indications, including: spinal cord injury, brain trauma, and peripheral nerve injury.
Parkinson's disease is a chronic, progressive degenerative disorder that involves a specialized region of the brain that controls muscle tone and coordination and affects over one million people in the United States. Most patients are affected in mid-life and usually develop hand tremors, muscle rigidity, and postural instability, among the many manifestations of the disease. The disease is caused by the degeneration of nerve cells that use dopamine as a chemical messenger. Treatment currently consists of administering drugs that increase the amount of dopamine in the affected regions of the brain or substitute for the lost dopamine. Unfortunately, there are no current treatments that can reverse, or even slow down, the progressive degeneration of the dopamine nerve cells in Parkinson's disease.