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Pioglitazone in Early Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT01280123
Recruitment Status : Completed
First Posted : January 20, 2011
Results First Posted : October 14, 2015
Last Update Posted : October 14, 2015
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
University of Rochester

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: Pioglitazone
Drug: placebo
Enrollment 210
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Period Title: Overall Study
Started 72 67 71
Completed 71 63 70
Not Completed 1 4 1
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo Total
Hide Arm/Group Description

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Total of all reporting groups
Overall Number of Baseline Participants 72 67 71 210
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 67 participants 71 participants 210 participants
61.3  (10.6) 58.8  (9.2) 59.0  (9.9) 59.7  (9.9)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 67 participants 71 participants 210 participants
Males 53 47 48 148
Females 19 20 23 62
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 67 participants 71 participants 210 participants
Non-Latino whites 58 63 63 184
Racial/Ethnic Minority 14 4 8 26
Years of education  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 67 participants 71 participants 210 participants
17.1  (3.1) 16.2  (3.3) 16.8  (3.0) 16.7  (3.1)
Right-handed  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 67 participants 71 participants 210 participants
Yes 62 62 62 186
No 10 5 9 24
Duration of PD symptoms (years)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 67 participants 71 participants 210 participants
2.3  (1.9) 2.0  (1.2) 2.3  (2.3) 2.2  (1.9)
Time since PD diagnosis (years)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 67 participants 71 participants 210 participants
0.8  (0.7) 0.7  (0.7) 0.8  (0.7) 0.7  (0.7)
Total Unified Parkinson's Disease Rating Scale (UPDRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
23.8  (9.9) 21.2  (8.8) 21.7  (8.7) 22.2  (9.2)
[1]
Measure Description: The Total UPDRS is the sum of parts I, II, and III. The possible range of the total UPDRS is from 0-176. Higher values indicate worse outcomes.
UPDRS mental   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
0.8  (0.9) 0.8  (0.9) 0.9  (1.1) 0.8  (1.0)
[1]
Measure Description: The UPDRS mental score is the sum of the questions in part I. The possible range of the UPDRS mental is from 0-16. Higher values indicate worse outcomes.
UPDRS motor   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
17.7  (7.7) 15.0  (7.1) 15.3  (6.5) 15.8  (7.1)
[1]
Measure Description: The UPDRS motor score is the sum of the questions in part III. The possible range of the UPDRS motor is from 0-108. Higher values indicate worse outcomes.
UPDRS ADL   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
5.9  (3.2) 5.5  (2.9) 5.5  (3.0) 5.6  (3.0)
[1]
Measure Description: The UPDRS ADL score is the sum of the questions in part II (activities of daily living). The possible range of the UPDRS ADL is from 0-52. Higher values indicate worse outcomes.
Ambulatory capacity   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
1.1  (0.9) 0.8  (0.8) 1.1  (0.9) 1.0  (0.9)
[1]
Measure Description: Ambulatory Capacity is calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS). It ranges from 0-20. Higher scores are worse.
Schwab and England Activities of Daily Living scale (SEADL)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
93.8  (4.9) 94.1  (5.0) 93.9  (5.0) 93.9  (4.9)
[1]
Measure Description: The modified Schwab and England Activities of Daily Living is a single question ranging from 0-100% with anchors for each 10% interval. Higher scores are better (100% completely independent- 0% vegetative).
Parkinson's Disease Questionnaire 39 (PDQ-39) Summary Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
8.5  (8.1) 8.1  (5.9) 10.6  (7.9) 9.1  (7.4)
[1]
Measure Description: The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson’s disease-specific health related quality. The total score ranges from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better quality of life.
Geriatric Depression Scale (GDS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
1.4  (1.4) 1.1  (1.3) 1.8  (1.9) 1.4  (1.6)
[1]
Measure Description: Short version. 15 questions. A score of 0 to 5 is normal. A score greater than 5 suggests depression.
Mattis-Dementia Rating scale   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 72 participants 67 participants 71 participants 210 participants
138.6  (8.2) 138.8  (10.2) 138  (11.4) 138.4  (9.9)
[1]
Measure Description: Mattis Dementia Rating scale (DRS-2) raw score is the sum of 5 raw sub-scores (attention has possible 37 points, initiation/perseveration has possible 37 points, construction has possible 6 points, conceptualization has possible 39 points, memory has possible 25 points). Total range is 0-144. Higher scores are better.
rasagiline/selegiline use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 67 participants 71 participants 210 participants
rasagiline use 60 57 60 177
selegiline use 12 10 11 33
[1]
Measure Description: Proportion of patients on stable regimen of either 1 mg/day rasagiline or 10 mg/day selegiline at baseline.
1.Primary Outcome
Title Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline to 44 Weeks
Hide Description

Change in total UPDRS score from baseline to 44 weeks (in subjects treated with rasagiline 1 mg/day or selegiline 10 mg/day).

The Total UPDRS is the sum of parts I, II, and III. The possible range of the total UPDRS is from 0-176. Higher values indicate worse outcomes.

The change is 44 weeks - baseline.

Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (Standard Error)
Unit of Measure: units on a scale
4.42  (0.95) 5.13  (0.99) 6.25  (0.96)
2.Secondary Outcome
Title Change in Ambulatory Capacity From Baseline to 44 Weeks
Hide Description

This is the sum of the 5 UPDRS questions regarding ambulatory capacity: falling, freezing, walking, gait, postural stability.

Ambulatory Capacity is calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS). It ranges from 0-20. Higher scores are worse. Change is 44 weeks - baseline.

Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.39
(0.16 to 0.61)
0.38
(0.07 to 0.70)
0.4
(0.17 to 0.64)
3.Secondary Outcome
Title Change in Schwab and England Scale From Baseline to 44 Weeks
Hide Description The modified Schwab and England Activities of Daily Living is a single question ranging from 0-100% with anchors for each 10% interval. Higher scores are better (100% completely independent- 0% vegetative).
Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-2.12
(-3.47 to -0.78)
-2.52
(-3.95 to -1.09)
-1.84
(-3.49 to -0.18)
4.Secondary Outcome
Title Change in Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 44 Weeks
Hide Description

The Parkinson's Disease Questionnaire (PDQ-39) is a short, 39 item measure of quality of life in subjects with Parkinson's disease. The questionnaire covers 8 aspects of quality of life: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort.

The total score ranges from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better quality of life.

Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.03
(0.47 to 3.59)
2.08
(0.32 to 3.84)
0.08
(-1.59 to 1.76)
5.Secondary Outcome
Title Change in the Mattis Dementia Rating Scale (DRS-2)From Baseline to 44 Weeks
Hide Description The Mattis dementia rating scale is a psychometric instrument designed to assess the extent and nature of dementia. Mattis Dementia Rating scale (DRS-2) raw score is the sum of 5 raw sub-scores (attention has possible 37 points, initiation/perseveration has possible 37 points, construction has possible 6 points, conceptualization has possible 39 points, memory has possible 25 points). Total range is 0-144. Higher scores are better.
Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.16
(-1.26 to 3.58)
2.11
(-0.41 to 4.63)
3.16
(0.66 to 5.65)
6.Secondary Outcome
Title Change in the 15-item Geriatric Depression Scale (GDS-15)From Baseline to 44 Weeks
Hide Description The Geriatric Depression Scale - 15 is a short 15 yes or no question instrument for assessing depression in the elderly. It has been found to be particularly useful in assessing depression in Parkinson's Disease. A score of 0 to 5 is normal. A score greater than 5 suggests depression.
Time Frame 44 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description:

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

Overall Number of Participants Analyzed 72 67 71
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.13
(-0.33 to 0.58)
0.38
(-0.10 to 0.85)
0.18
(-0.37 to 0.72)
Time Frame All events during study period (defined as from signing consent to conclusion of study participation 44 weeks).
Adverse Event Reporting Description Adverse event data was elicited by asking an open ended question "What unusual symptoms or medical problems have you experienced since the last visit?"
 
Arm/Group Title 15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Hide Arm/Group Description

15 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

45 mg pioglitazone

Pioglitazone: Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: 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 begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Placebo

placebo: Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

All-Cause Mortality
15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/72 (8.33%)      9/67 (13.43%)      3/71 (4.23%)    
Cardiac disorders       
Atrial fibrillation  1  0/72 (0.00%)  0/67 (0.00%)  1/71 (1.41%) 
Atrial flutter  1  1/72 (1.39%)  0/67 (0.00%)  0/71 (0.00%) 
Coronary artery stenosis  1  0/72 (0.00%)  0/67 (0.00%)  1/71 (1.41%) 
Myocardial infarction  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Gastrointestinal disorders       
Intestinal obstruction  1  1/72 (1.39%)  1/67 (1.49%)  0/71 (0.00%) 
General disorders       
Chest pain  1  0/72 (0.00%)  0/67 (0.00%)  1/71 (1.41%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  1/72 (1.39%)  0/67 (0.00%)  0 0/71 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc degeneration  1  1/72 (1.39%)  0/67 (0.00%)  0/71 (0.00%) 
Intervertebral disc protrusion  1  1/72 (1.39%)  0/67 (0.00%)  0/71 (0.00%) 
Spondylolisthesis  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Osteoarthritis  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Nervous system disorders       
Transient ischemic attack  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Dizziness  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Psychiatric disorders       
Confusional state  1  0/72 (0.00%)  2/67 (2.99%)  0/71 (0.00%) 
Disorientation  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Reproductive system and breast disorders       
Ovarian cyst ruptured  1  1/72 (1.39%)  0/67 (0.00%)  0/71 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Hypoxia  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Respiratory failure  1  0/72 (0.00%)  1/67 (1.49%)  0/71 (0.00%) 
Surgical and medical procedures       
Knee arthroplasty  1  0/72 (0.00%)  0/67 (0.00%)  1/71 (1.41%) 
Vascular disorders       
Hypertension  1  0/72 (0.00%)  0/67 (0.00%)  1/71 (1.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
15 mg Pioglitazone 45 mg Pioglitazone Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   63/72 (87.50%)      51/67 (76.12%)      59/71 (83.10%)    
Eye disorders       
Cataract  1  4/72 (5.56%)  2/67 (2.99%)  0/71 (0.00%) 
Gastrointestinal disorders       
Constipation  1  1/72 (1.39%)  3/67 (4.48%)  5/71 (7.04%) 
Diarrhoea  1  7/72 (9.72%)  3/67 (4.48%)  3/71 (4.23%) 
Nausea  1  6/72 (8.33%)  7/67 (10.45%)  3/71 (4.23%) 
General disorders       
Fatigue  1  8/72 (11.11%)  2/67 (2.99%)  3/71 (4.23%) 
Oedema  1  3/72 (4.17%)  9/67 (13.43%)  6/71 (8.45%) 
Infections and infestations       
Upper respiratory tract infection  1  3/72 (4.17%)  3/67 (4.48%)  4/71 (5.63%) 
Urinary tract infection  1  2/72 (2.78%)  3/67 (4.48%)  4/71 (5.63%) 
Investigations       
Blood creatine phosphokinase increased  1  12/72 (16.67%)  9/67 (13.43%)  11/71 (15.49%) 
Blood creatinine increased  1  4/72 (5.56%)  4/67 (5.97%)  1/71 (1.41%) 
Blood urea increased  1  5/72 (6.94%)  1/67 (1.49%)  0/71 (0.00%) 
Protein urine present  1  2/72 (2.78%)  2/67 (2.99%)  4/71 (5.63%) 
Weight increased  1  1/72 (1.39%)  5/67 (7.46%)  0/71 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/72 (1.39%)  1/67 (1.49%)  5/71 (7.04%) 
Nervous system disorders       
Dizziness  1  5/72 (6.94%)  5/67 (7.46%)  6/71 (8.45%) 
Tremor  1  4/72 (5.56%)  0/67 (0.00%)  1/71 (1.41%) 
Renal and urinary disorders       
Proteinuria  1  4/72 (5.56%)  3/67 (4.48%)  2/71 (2.82%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/72 (4.17%)  2/67 (2.99%)  4/71 (5.63%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Tanya Simuni, MD
Organization: Northwestern University
Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT01280123     History of Changes
Other Study ID Numbers: FS-ZONE
5U01NS043128-12 ( U.S. NIH Grant/Contract )
First Submitted: December 3, 2010
First Posted: January 20, 2011
Results First Submitted: August 13, 2015
Results First Posted: October 14, 2015
Last Update Posted: October 14, 2015