Final Phase II GPI 1485 (NIL-A) Imaging Data Presented At the Annual Meeting of the American Academy of Neurology
BALTIMORE, April 17 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (Nasdaq: GLFD - news) announced today that the final imaging data analysis from a Phase II clinical trial of GPI 1485 (formerly known as NIL-A) is being presented today at the Annual Meeting of the American Academy of Neurology in Denver, Colorado by Dr. John Seibyl and his colleagues. The data presented suggest that GPI 1485 administered orally for six months may retard the loss of dopamine transporters, a marker of disease progression, in patients with Parkinson's disease.
About the Phase II Clinical Trial
The Phase II clinical trial was 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 300 patients were enrolled and randomly assigned to receive either placebo, low dose GPI 1485 (800 mg/day), or high dose GPI 1485 (4000 mg/day), administered orally for six months (24 weeks). To be eligible for the study, patients had to be optimally treated with antiparkinsonian drugs and have stable clinical symptoms. The principal efficacy endpoint in the study was the change in the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) during the 24 weeks of treatment.
The other major efficacy endpoint in the study was the change in dopamine transporter density, measured using DOPASCAN® Injection. Dopamine transporter density is a marker of dopamine nerve terminal density since the transporters are located on the surface of the nerve terminals. SPECT brain scans were obtained with DOPASCAN® Injection at baseline and six months after randomization in 105 of the patients enrolled in the study. The SPECT scans were initially read by a single, experienced evaluator who was blinded to the treatment given. Previous studies have shown that patients with Parkinson's disease lose about 5 - 6% of their dopamine transporters per year when assessed using SPECT scanning with DOPASCAN® Injection. Consequently, it was expected that the placebo group in the current study would lose approximately 2.5 - 3% of their dopamine transporters over the course of six months.
Clinical Trial Results
The preliminary results of the trial were originally reported in July 2001, and demonstrated that 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.
The preliminary imaging data showed that the mean percent change from baseline in the density of dopamine transporters was only -0.15% in placebo patients, much less than that predicted, -1.2% in the low dose treatment group, and +2.5% in the high dose treatment group. These results included data from two patients who had SPECT score results that were inconsistent with the clinical course of Parkinson's disease.
Another assessment of the SPECT scores was obtained using a second experienced evaluator who was also blinded to the treatment given and used the same methods as the first evaluator to quantitate the SPECT scans. The results from the first evaluation and the second evaluation were highly correlated (r = 0.97, p = 0.0001). All of the data from the second evaluation were consistent with the clinical course of Parkinson's disease. The results from the second evaluation showed the mean percent change from baseline in the density of dopamine nerve terminals was -2.4% in the placebo group, a result consistent with pre-study expectations, -3.5% in the low dose treatment group, and +1.6% in the high dose treatment group, (p = 0.13 placebo vs. high dose group).
An evaluation of the baseline SPECT values indicated that there were 11 patients (4 placebo, 3 low dose, 4 high dose) with SPECT values greater than 4 and as high as 7. These patients were much younger and had less severe disease as measured by SPECT and UPDRS scores. If these 11 patients are excluded, and the remaining patients with moderate Parkinson's disease are evaluated, the mean percent change from baseline in the density of dopamine nerve terminals was -3.1% in the placebo group, -1.4% in the low dose treatment group, and +2.5% in the high dose treatment group (p = 0.06 for linear dose response).
``The final analysis from our study shows that treatment with placebo resulted in expected reductions in dopamine transporter density over six months, while treatment with high dose GPI 1485 resulted in a modest increase in the density of dopamine transporters. Although the overall analysis did not achieve conventional levels of statistical significance, the data are consistent with a disease-modifying effect of GPI 1485,'' remarked John P. Seibyl, M.D., Executive Director and Senior Scientist, The Institute for Neurodegenerative Disorders, New Haven, CT. ``While these results are from exploratory data analyses and must be interpreted with caution, this is a very promising result which we have never before observed in patients participating in neuroimaging studies of Parkinson's disease progression. A confirmatory study, with a greater number of patients treated for a longer duration of time will be needed to confirm these findings.''... |
