gpi-1485 and Parkinson-Disease

GPI-1485 is a neuroimmunophilin ligand that binds to FK-506-binding proteins and is under development by Guilford for the potential treatment of erectile dysfunction following nerve injury during prostate resection and Parkinson's disease. In August 2002, phase II clinical trials investigating GPI-1485 for Parkinson's disease commenced, and in November 2003, further phase II trials commenced for post-prostatectomy erectile dysfunction.

Topics: Administration, Oral; Animals; Antiparkinson Agents; Clinical Trials, Phase II as Topic; Erectile Dysfunction; Humans; Male; Parkinson Disease; Patents as Topic; Prostatectomy; Structure-Activity Relationship; Tacrolimus

Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.. AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.. clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.

Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; National Institutes of Health (U.S.); Parkinson Disease; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Tacrolimus; Treatment Outcome; United States

To assess the predictive value of baseline measures of impairment, disability, and quality of life for the timing of initiation of symptomatic treatment in early Parkinson disease (PD).. Inception cohort analysis.. Ambulatory population from multiple sites in the United States and Canada.. Four hundred thirteen patients with early, untreated PD who participated in 2 double-blind trials that assessed the potential of experimental drugs to serve as disease-modifying agents in PD. Intervention Participants were randomized into treatment groups: creatine (n = 67), minocycline (n = 66), coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). Main Outcome Measure Time between baseline assessment and need for the initiation of symptomatic treatment for PD. The following baseline variables were assessed for their relation to the main outcome measure, while adjusting for possible treatment effect: sex; age; level of education; race/ethnicity; disease duration; occupational status; and Unified Parkinson Disease Rating Scale (UPDRS), Medical Outcomes Study Short Form Survey, Modified Rankin Scale, Schwab and England Activities of Daily Living Scale, Total Functional Capacity Scale, 39-item Parkinson Disease Questionnaire, and Geriatric Depression Scale scores. Variables reaching statistical threshold in univariate analyses (alpha = .15) were entered into a multivariable Cox proportional hazards regression model using time to symptomatic treatment as the dependent variable.. Approximately half (48.5%) of the participants reached end point within 12 months. Higher baseline impairment and disability, as determined by UPDRS III (motor section), UPDRS II (activities of daily living section, participant rating), and Modified Rankin Scale scores and level of education were independently associated with an earlier need for symptomatic treatment.. In early PD, greater impairment and disability and higher level of education are independently associated with an earlier need for symptomatic treatment.

Topics: Activities of Daily Living; Adult; Aged; Antiparkinson Agents; Creatine; Disability Evaluation; Disease Management; Drug Administration Schedule; Endpoint Determination; Female; Humans; Male; Middle Aged; Minocycline; Mobility Limitation; Neuropsychological Tests; Parkinson Disease; Predictive Value of Tests; Severity of Illness Index; Surveys and Questionnaires; Tacrolimus; Time Factors; Ubiquinone

To determine if future studies of coenzyme Q(10) and GPI-1485 in Parkinson disease (PD) may be warranted.. We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold.. The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed.. Coenzyme Q(10) and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies.

Topics: Aged; Coenzymes; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Nausea; Parkinson Disease; Tacrolimus; Ubiquinone