A Multi-Center, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early Parkinson[Single Quote]s Disease.
Multi-center, double-blind, placebo controlled clinical trial of two dosages of oral pioglitazone (15 mg and 45 mg) for safety, tolerability, and futility.
Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but no more than 8 months, will be randomized to one of two dosages of oral pioglitazone (15 mg and 45 mg) or matching placebo.
A total of 216 subjects from approximately 50 sites in the US and Canada will be randomized to 15 mg pioglitazone (n=72), 45 mg pioglitazone (n=72), or placebo (n=72). Each subject will be followed for 44 weeks to measure the following efficacy variables:
Change in individual Parts I-IV of the UPDRS
* Change in Ambulatory Capacity (sum of 5 UPDRS questions: falling, freezing, walking, gait, postural stability)
* Change in Schwab and England ADL
* Change in PDQ-39
* Change on the Mattis Dementia Rating Scale (DRS)
* Change on the 15-item Geriatric Depression Scale (GDS-15)
* Proportion of subjects who complete the study on their assigned dose of study drug
Safety and Tolerability Variables:
* Adverse event frequency and severity, changes in vital signs, clinical laboratory values.
* 40-item University of Pennsylvania Smell Identification Test (UPSIT)
* Blood- and urine-based biomarkers of possible response to pioglitazone:
o Levels of PGC-1(RegisteredTM) mRNA,
o Levels of mRNA for genes regulated by PGC-1(RegisteredTM),
1. Willing and able to give informed consent.
2. Men and women with idiopathic PD of less than 5 years duration from diagnosis Hoehn and Yahr Stage < or =2.
3. On stable dosage of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but not more than 8 months prior to baseline. Expected to remain on stable dose of rasagiline or selegiline as the only treatment for their PD for the duration of the study (44 weeks).
4. Diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs (resting tremor, rigidity) being present, without any other known or suspected cause of parkinsonism. The clinical signs must be asymmetric.
5. Subjects may be taking stable doses (30 days) of anticholinergics, creatine (< 5gm/day) but must be expected to remain on the same dose.
6. Age > 30 years.
7. Women who are not postmenopausal or surgically sterile must use a medically accepted contraceptive regimen for at least 60 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug. Reliable forms of contraception include oral, implanted, or injected contraceptives; intrauterine devices in place for at least 3 months; or adequate barrier methods in conjunction with spermicide (abstinence is considered an acceptable contraceptive regimen) or partner vasectomy. Women must have a pregnancy test unless they are at least 2 years postmenopausal or surgically sterile. Women of childbearing potential must have a negative pregnancy test at baseline and be non-lactating.
Additionally, subjects will be made aware that we are not certain if co-administration of study drug with hormonal contraceptives lessens the effectiveness of the birth control. Therefore, additional precautions, such as a secondary birth control method may be warranted to prevent pregnancy