ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease (APEX-PD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00880620
Recruitment Status : Completed
First Posted : April 14, 2009
Results First Posted : February 22, 2016
Last Update Posted : August 17, 2017
Sponsor:
Information provided by (Responsible Party):
IMPAX Laboratories, Inc.

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: Placebo
Drug: IPX066 95 mg LD
Drug: IPX066 145 mg LD
Drug: IPX066 195 mg LD
Drug: IPX066 245 mg LD
Enrollment 381
Recruitment Details First patient enrolled: 4/13/2009 Last patient out 10/05/2010
Pre-assignment Details Following enrollment, subjects were randomized into one of the four treatment groups.
Arm/Group Title Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD
Hide Arm/Group Description Placebo capsules were used IPX066 capsule containing 145 mg levodopa and 36.25 mg carbidopa IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa IPX066 capsules that contained 390 mg levodopa and 97.5 mg carbidopa
Period Title: Overall Study
Started [1] 92 87 104 98
Week 4 88 79 94 86
Week 9 80 73 88 78
Week 16 74 73 87 74
Week 23 71 72 85 74
Completed [2] 71 72 83 74
Not Completed 21 15 21 24
Reason Not Completed
Adverse Event             4             5             15             15
Death             0             0             1             0
Lack of Efficacy             12             4             0             1
Lost to Follow-up             0             1             1             0
Protocol Violation             0             1             0             2
Withdrawal by Subject             4             3             1             3
Noncompliance             0             0             1             1
Not specified             1             1             2             2
[1]
Baseline
[2]
Week 30
Arm/Group Title Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD Total
Hide Arm/Group Description Placebo capsules were used IPX066 capsules containing 145 mg levodopa and 36.25 mg carbidopa IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa IPX066 capsules containing 390 mg levodopa and 97.5 mg carbidopa Total of all reporting groups
Overall Number of Baseline Participants 92 87 104 98 381
Hide Baseline Analysis Population Description
Baseline Analysis Population is all treated
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
65.4  (9.43) 63.8  (9.81) 65.2  (9.73) 64.8  (9.32) 64.8  (9.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
Female
40
  43.5%
40
  46.0%
45
  43.3%
44
  44.9%
169
  44.4%
Male
52
  56.5%
47
  54.0%
59
  56.7%
54
  55.1%
212
  55.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
Hispanic or Latino
3
   3.3%
5
   5.7%
7
   6.7%
4
   4.1%
19
   5.0%
Not Hispanic or Latino
87
  94.6%
78
  89.7%
91
  87.5%
89
  90.8%
345
  90.6%
Unknown or Not Reported
2
   2.2%
4
   4.6%
6
   5.8%
5
   5.1%
17
   4.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
Asian 1 0 0 1 2
Black or African American 0 0 2 0 2
White 90 87 102 96 375
Other 1 0 0 1 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
Canada 10 9 9 9 37
Latvia 1 1 0 0 2
Romania 13 13 15 14 55
United States 30 29 37 38 134
Ukraine 28 29 32 26 115
Lithuania 7 4 8 8 27
Estonia 3 2 3 3 11
Age at Parkinson's disease onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
63.7  (9.48) 61.7  (10.71) 63.6  (10.43) 63.0  (9.38) 63.0  (10.00)
Duration of Parkinson's disease  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
1.8  (2.01) 2.3  (3.08) 1.8  (1.85) 2.0  (2.33) 2.0  (2.34)
UPDRS Parts II and III Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
36.3  (11.89) 36.1  (13.56) 38.1  (15.63) 36.3  (13.04) 36.7  (13.63)
[1]
Measure Description:

Unified Parkinson’s Disease Rating Scale (UPDRS) – Four Parts Higher score values represent a worse outcome.

Subscales II and III were summed:

Part I: Mentation, Behavior and Mood – 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living – 13 questions 5-17 Score range: 0-52 Part III: Motor Examination – 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) – 11 questions Score range: 0-25

Hoehn and Yahr Stage   [1] 
Measure Type: Number
Unit of measure:  Units on a scale
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
Stage I 7 6 13 14 40
Stage II 69 62 65 62 258
Remaining 16 19 26 22 83
[1]
Measure Description:

Hoehn and Yahr Staging of Parkinson’s Disease: Stages move from 1 – 5 with the worse outcome stage being Stage 5.

Stage 1 = Symptoms on one side of the body only. Stage 2 = Symptoms on both sides of the body, No impairment of balance. Stage 3 = Balance impairment. Mild to moderate disease. Physically independent. Stage 4 = Severe disability but still able to walk or stand unassisted. Stage 5 = Wheelchair bound or bedridden unless assisted.

MMSE   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 92 participants 87 participants 104 participants 98 participants 381 participants
28.9  (1.18) 29.0  (1.27) 28.7  (1.21) 28.9  (1.18) 28.9  (1.21)
[1]
Measure Description: The Mini–Mental State Examination (MMSE) is a 30-point questionnaire that is used extensively to measure cognitive impairment. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10–18 points) or mild (19–23 points) cognitive impairment.
1.Primary Outcome
Title Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30
Hide Description

Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at Week 30 (End of Study).

Unified Parkinson’s Disease Rating Scale (UPDRS) – Four Parts Higher score values represent a worse outcome.

Subscales II and III were summed:

Part I: Mentation, Behavior and Mood – 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living – 13 questions 5-17 Score range: 0-52 Part III: Motor Examination – 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) – 11 questions Score range: 0-25

Time Frame Week 30
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis included all treated subjects with at least one efficacy measurement after dosing. Subjects who had no post-baseline efficacy assessments (N4) and those who had early termination assessments>3 days after last dose and no other post-baseline measurements (N16) were not included in the efficacy analysis set. Randomized (381)-(4+16) = 361.
Arm/Group Title Placebo IPX066 145mg LD IPX066 245 mg LD IPX066 390 mg LD
Hide Arm/Group Description:
Placebo capsules were used
IPX066 capsules containing 145 mg levodopa and 36.25 mg carbidopa
IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa
IPX066 capsules containing 390 mg levodopa and 97.5 mg carbidopa
Overall Number of Participants Analyzed 90 82 99 90
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.6  (10.37) -11.7  (10.97) -12.9  (11.42) -14.9  (11.85)
2.Secondary Outcome
Title Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score
Hide Description Change from Baseline in Parkinson's disease Questionnaire 39 (PDQ-39) at Weeks 4, 9, 16, 23 and 30 or early discontinuation was collected. The PDQ-39 is a self-reported questionnaire consisting of 39 questions regarding the subjects mobility and the responses consist of "Never" (better in outcome), (value 0), "Occasionally" (value 1), "Sometimes" (value 2), , "Often" (value 3), and "Always" (value 4), (worse in outcome). The minimum possible score is "0" and the maximum is "156". The outcome measure calculated was the change from baseline to end of study in mean PDQ-39 score. Negative values indicate a better result.
Time Frame Baseline and Week 30 (or End of Study)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects who had no postbaseline efficacy assessments (N=4) and those who had early termination assessments >3 days after last dose and no other postbaseline measurements (N=16) were not included in the efficacy analysis. 2 subjects without a baseline measurement, 1 each from 145mg and 390mg arm were also excluded. Randomized 381-4-16-2=359.
Arm/Group Title IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD Placebo
Hide Arm/Group Description:
IPX066 capsules containing 145 mg levodopa and 36.25 mg carbidopa
IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa
IPX066 capsules containing 390 mg levodopa and 97.5 mg carbidopa
Placebo capsules were used
Overall Number of Participants Analyzed 81 99 89 90
Mean (Standard Deviation)
Unit of Measure: score on a scale
-4.4  (12.18) -3.8  (12.16) -6.0  (12.30) 0.6  (11.10)
Time Frame 1 year, 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD
Hide Arm/Group Description Placebo capsules were used IPX066 capsules containing 145 mg levodopa and 36.25 mg carbidopa IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa IPX066 capsules containing 390 mg levodopa and 97.5 mg carbidopa
All-Cause Mortality
Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/92 (3.26%)      4/87 (4.60%)      5/104 (4.81%)      2/98 (2.04%)    
Cardiac disorders         
Acute myocardial infarction * 1  0/92 (0.00%)  0 1/87 (1.15%)  1 0/104 (0.00%)  0 0/98 (0.00%)  0
Atrioventricular block complete * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 1/104 (0.96%)  1 0/98 (0.00%)  0
Coronary artery disease * 1  0/92 (0.00%)  0 1/87 (1.15%)  1 0/104 (0.00%)  0 0/98 (0.00%)  0
Myocardial infarction * 1  0/92 (0.00%)  0 1/87 (1.15%)  1 0/104 (0.00%)  0 0/98 (0.00%)  0
Gastrointestinal disorders         
Abdominal strangulated hernia * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 1/104 (0.96%)  1 0/98 (0.00%)  0
Infections and infestations         
Escherichia urinary tract infection * 1  0/92 (0.00%)  0 1/87 (1.15%)  1 0/104 (0.00%)  0 0/98 (0.00%)  0
Urinary tract infection * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 0/104 (0.00%)  0 1/98 (1.02%)  1
Urosepsis * 1  1/92 (1.09%)  1 0/87 (0.00%)  0 0/104 (0.00%)  0 0/98 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Osteoarthritis * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 1/104 (0.96%)  1 0/98 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Non-Hodgkin's Lymphoma * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 1/104 (0.96%)  1 0/98 (0.00%)  0
Nervous system disorders         
Cerebrovascular accident * 1  1/92 (1.09%)  1 0/87 (0.00%)  0 0/104 (0.00%)  0 0/98 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 0/104 (0.00%)  0 1/98 (1.02%)  1
Emphysema * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 0/104 (0.00%)  0 1/98 (1.02%)  1
Surgical and medical procedures         
Coronary Artery Bypass * 1  0/92 (0.00%)  0 0/87 (0.00%)  0 1/104 (0.96%)  1 0/98 (0.00%)  0
Prostatectomy * 1  1/92 (1.09%)  1 0/87 (0.00%)  0 0/104 (0.00%)  0 0/98 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo IPX066 145 mg LD IPX066 245 mg LD IPX066 390 mg LD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/92 (28.26%)      27/87 (31.03%)      47/104 (45.19%)      48/98 (48.98%)    
Gastrointestinal disorders         
Nausea * 1  8/92 (8.70%)  12/87 (13.79%)  20/104 (19.23%)  20/98 (20.41%) 
Dry Mouth * 1  1/92 (1.09%)  3/87 (3.45%)  2/104 (1.92%)  7/98 (7.14%) 
Vomiting * 1  3/92 (3.26%)  2/87 (2.30%)  2/104 (1.92%)  5/98 (5.10%) 
Constipation * 1  1/92 (1.09%)  2/87 (2.30%)  6/104 (5.77%)  2/98 (2.04%) 
Nervous system disorders         
Headache * 1  10/92 (10.87%)  6/87 (6.90%)  13/104 (12.50%)  17/98 (17.35%) 
Dizziness * 1  5/92 (5.43%)  8/87 (9.20%)  20/104 (19.23%)  12/98 (12.24%) 
Dyskinesia * 1  0/92 (0.00%)  2/87 (2.30%)  4/104 (3.85%)  5/98 (5.10%) 
Psychiatric disorders         
Insomnia * 1  3/92 (3.26%)  2/87 (2.30%)  9/104 (8.65%)  6/98 (6.12%) 
Abnormal dreams * 1  0/92 (0.00%)  2/87 (2.30%)  6/104 (5.77%)  5/98 (5.10%) 
Anxiety * 1  0/92 (0.00%)  2/87 (2.30%)  3/104 (2.88%)  5/98 (5.10%) 
Depression * 1  5/92 (5.43%)  1/87 (1.15%)  2/104 (1.92%)  2/98 (2.04%) 
Vascular disorders         
Orthostatic Hypotension * 1  1/92 (1.09%)  1/87 (1.15%)  1/104 (0.96%)  5/98 (5.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Publication of the results of the Study conducted at the Site shall not be made before the first multi-site publication by Sponsor.
Results Point of Contact
Name/Title: Michelle Landolfi, PhD, Senior Director Regulatory Affairs
Organization: Impax Laboratories, Inc.
Phone: 510-240-6496
Responsible Party: IMPAX Laboratories, Inc.
ClinicalTrials.gov Identifier: NCT00880620     History of Changes
Other Study ID Numbers: IPX066-B08-05
First Submitted: April 3, 2009
First Posted: April 14, 2009
Results First Submitted: December 7, 2015
Results First Posted: February 22, 2016
Last Update Posted: August 17, 2017