A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066

• Sponsor: Impax Laboratories, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01130493
• Collaborator: (none)
• Enrollment: 110
• Locations: 24
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study to compare the efficacy of IPX066 and CLE in subjects with advanced Parkinson's disease.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: IPX066; Drug: CLE	Phase 3

Detailed Description

This is a randomized, double-blind, double-dummy, 2 treatment, 2-period crossover study followed by an open-label extension study period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson's Disease
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: IPX066-CLE-OLE Dose conversion from CLE to IPX066, IPX066 (Part 1 Period 1), Open-label IPX066, CLE (Part 1 Period 2), OLE (Part 2)	Drug: IPX066; experimental product; Other Names: extended-release carbidopa-levodopa ; Drug: CLE; active comparator; Other Names: carbidopa/levodopa/entacapone
Other: CLE-IPX066-OLE Dose conversion from CLE to IPX066, CLE (Part 1 Period 1), Open-label IPX066, IPX066 (Part 1 Period 2), OLE (Part 2)	Drug: IPX066; experimental product; Other Names: extended-release carbidopa-levodopa ; Drug: CLE; active comparator; Other Names: carbidopa/levodopa/entacapone

Outcome Measures

Primary Outcome Measures

1. Percentage of "OFF" Time During Waking Hours [3 days of data immediately prior to the end of each 2 week treatment period]

   Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean percentage of "OFF" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.

Secondary Outcome Measures

1. Total "OFF" Time During Waking Hours [3 days of data immediately prior to the end of each 2 week treatment period]

   Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "Off" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.

2. Total "On" With No Troublesome Dyskinesia [3 days of data immediately prior to the end of each 2 week treatment period]

   Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "On" with No Troublesome Dyskinesia was calculated. "On" Time is when medication is providing benefit with regard to mobility, slowness, and stiffness.

3. UPDRS Part II Plus Part III [End of each double-blind treatment period.]

   Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). Part II consists of 14 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 72. Part III consists of 27 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 108. The UPDRS Part II Plus Part III scores ranged from 0 (no problems with daily living or mobility) to 180 (severe problems with daily living and mobility.

4. Subject Preference [End of Study (week 11)]

   Subjects who completed both treatments were asked to indicate a preference for Treatment Period 1 or Treatment Period 2 or no preference. Preferences for a particular treatment period were mapped to the associated treatment and reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with idiopathic Parkinson's Disease (PD).

2. At least 30 years old at the time of PD diagnosis.

3. Currently being treated with carbidopa/levodopa/entacapone (CLE) and on a stable regimen of conventional LD for at least 4 weeks and:

• Requiring a total daily levodopa (LD) dose of at least 400 mg

• Having a minimum dosing frequency of four times per day.

• Individual CD-LD or CLE doses that contain an LD dose which is a multiple of 50 mg.

1. Able to differentiate "on" state from "off" state.

2. Have predictable "off" periods.

3. Amantadine, anticholinergics, selective monoamine oxidase (MAO) type B inhibitors (e.g., selegiline, rasagiline) or dopamine agonists are allowed as long as the doses and regimens have been stable for at least 4 weeks prior to Screening and the therapy is intended to be constant throughout the course of the study.

4. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month afterward.

Exclusion Criteria:

1. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome.

2. Nonresponsive to LD therapy.

3. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation.

4. Received within 4 weeks of Screening or planning to take during participation in the clinical study: any controlled-release LD product, tolcapone, apomorphine, nonselective MAO inhibitors, or antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder.

5. Allergy or hypersensitivity to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice.

6. History of or currently active psychosis.

7. Active or prior medical conditions such as peptic ulcers or prior surgical (e.g., bowel) procedures that would interfere with LD absorption.

8. Active or history of narrow-angle glaucoma.

9. History of malignant melanoma or a suspicious undiagnosed skin lesion.

10. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome or nontraumatic rhabdomyolysis.

11. Received any investigational medications during the 4 weeks prior to Screening.

12. Unable to swallow large pills (e.g., large vitamin pills).

13. Pregnant or breastfeeding.

14. Subjects who are unable to complete a symptom diary.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Margolin Brain Institute	Fresno	California	United States	93720
2	The Parkinson's Institute in Sunnyvale	Sunnyvale	California	United States	94085
3	UM Movement Disorders Center	Miami	Florida	United States	33136
4	Charlotte Neurological Services	Port Charlotte	Florida	United States	33980
5	USF Parkinson's and Movement Disorders Center	Tampa	Florida	United States	33606
6	Quest Research Institute	Bingham Farms	Michigan	United States	48025
7	University Health Systems	Las Vegas	Nevada	United States	89102
8	Parkinson's Disease and Movement Disorders Center of Long Island	Commack	New York	United States	11725
9	Kingston Neurological Associates	Kingston	New York	United States	12401
10	University Neurology, Inc	Cincinnati	Ohio	United States	45219
11	Sentara Neurological Associates	Virginia Beach	Virginia	United States	23456
12	Booth Gardner Parkinson's Care Center	Kirkland	Washington	United States	98034
13	Hôpital Gabriel Montpied-Service de Neurologie A-	Clermont-Ferrand Cedex 1		France	63003
14	Service de neurologie-Hôpital de la Timone-	Marseille		France	13385
15	Praxis für Neurologie, Psychiatrie und Psychotherapie Achim	Achim		Germany	28832
16	Praxis Dres. Bitter/Schumann	Bochum		Germany	44805
17	Klinikum rechts der Isar der Technischen Universität München	München		Germany	81675
18	Klinik für Neurologie, Stadtroda	Stadtroda		Germany	07646
19	RKU, Neurologische Klinik der Universität Ulm	Ulm		Germany	89081
20	Casa di Cura Villa Margherita	Arcugnano		Italy	36057
21	San Raffaele Cassino, San Raffaele Cassino,	Cassino		Italy	03043
22	Dipartimento di Oncologia e Neuroscienze, Università G. D'Annunzio	Chieti		Italy	66013
23	Ospedale della Misericordia	Grosseto		Italy	58100
24	IRCCS San Raffaele Pisana	Roma		Italy	163

Sponsors and Collaborators

• Impax Laboratories, LLC

Investigators

• Study Director: Impax Study Director, Impax Laboratories, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Impax Laboratories, LLC
• ClinicalTrials.gov Identifier: NCT01130493
• Other Study ID Numbers: IPX066-B09-06
• First Posted: May 26, 2010
• Last Update Posted: Oct 29, 2019
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Parkinson Disease; Levodopa; Carbidopa; Entacapone; Carbidopa, levodopa drug combination

Study Results

Participant Flow

Recruitment Details	Date first patient enrolled: March 22, 2011 Date last patient completed: January 12, 2012
Pre-assignment Detail	Following enrollment, all subjects were converted from stable doses of CLE to IPX066 prior to randomization. Following dose conversion, subjects were randomized into one of the two treatment sequences.

Arm/Group Title	IPX066 Conversion	IPX066-Open-label IPX066 Washout-CLE-OLE	CLE-Open Label IPX066 Washout-IPX066-OLE
Arm/Group Description	All subjects were converted to IPX066 during an open-label period	IPX066 (Per Protocol: Part 1 Period 1), Open-label washout IPX066, CLE (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)	CLE (Per Protocol: Part 1 Period 1), Open-label washout IPX066, IPX066 (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)
Period Title: Open-label Dose Conversion to IPX066
STARTED	110	0	0
COMPLETED	91	0	0
NOT COMPLETED	19	0	0
Period Title: Open-label Dose Conversion to IPX066
STARTED	0	48	43
COMPLETED	0	46	43
NOT COMPLETED	0	2	0
Period Title: Open-label Dose Conversion to IPX066
STARTED	0	46	43
COMPLETED	0	45	41
NOT COMPLETED	0	1	2
Period Title: Open-label Dose Conversion to IPX066
STARTED	0	45	41
COMPLETED	0	45	39
NOT COMPLETED	0	0	2
Period Title: Open-label Dose Conversion to IPX066
STARTED	0	39	35
COMPLETED	0	36	30
NOT COMPLETED	0	3	5

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants who were randomized to receive either IPX066 or IR CD-LD in Part 1 of the study and then IPX066 in Part 2 (open-label extension).
Overall Participants	91
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	50 54.9%
>=65 years	41 45.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (9.34)
Sex: Female, Male (Count of Participants)
Female	23 25.3%
Male	68 74.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 8.8%
Not Hispanic or Latino	79 86.8%
Unknown or Not Reported	4 4.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	89 97.8%
More than one race	0 0%
Unknown or Not Reported	2 2.2%
Region of Enrollment (participants) [Number]
United States	44 48.4%
Italy	26 28.6%
Germany	21 23.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of "OFF" Time During Waking Hours
Description	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean percentage of "OFF" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.
Time Frame	3 days of data immediately prior to the end of each 2 week treatment period

Outcome Measure Data

Analysis Population Description

Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2

Arm/Group Title	IPX066	CLE (Active Comparator)
Arm/Group Description	Participants who received IPX066 in either Period 1 or Period 2	Participants who received CLE in either Period 1 or Period 2
Measure Participants	83	83
Mean (Standard Deviation) [Percent]	23.98 (16.242)	32.48 (21.917)

2. Secondary Outcome

Title	Total "OFF" Time During Waking Hours
Description	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "Off" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.
Time Frame	3 days of data immediately prior to the end of each 2 week treatment period

Outcome Measure Data

Analysis Population Description

Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2

Arm/Group Title	IPX066	CLE (Active Comparator)
Arm/Group Description	Participants who received IPX066 in either Period 1 or Period 2	Participants who received CLE in either Period 1 or Period 2
Measure Participants	83	83
Mean (Standard Deviation) [hours]	3.82 (2.558)	5.22 (3.672)

3. Secondary Outcome

Title	Total "On" With No Troublesome Dyskinesia
Description	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "On" with No Troublesome Dyskinesia was calculated. "On" Time is when medication is providing benefit with regard to mobility, slowness, and stiffness.
Time Frame	3 days of data immediately prior to the end of each 2 week treatment period

Outcome Measure Data

Analysis Population Description

Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2

Arm/Group Title	IPX066	CLE (Active Comparator)
Arm/Group Description	Participants who received IPX066 in either Period 1 or Period 2	Participants who received CLE in either Period 1 or Period 2
Measure Participants	83	83
Mean (Standard Deviation) [hours]	11.36 (3.259)	9.98 (3.764)

4. Secondary Outcome

Title	UPDRS Part II Plus Part III
Description	Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). Part II consists of 14 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 72. Part III consists of 27 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 108. The UPDRS Part II Plus Part III scores ranged from 0 (no problems with daily living or mobility) to 180 (severe problems with daily living and mobility.
Time Frame	End of each double-blind treatment period.

Outcome Measure Data

Analysis Population Description

Participants who completed both treatment periods

Arm/Group Title	IPX066	CLE (Active Comparator)
Arm/Group Description	Participants who received IPX066 in either Period 1 or Period 2	Participants who received CLE in either Period 1 or Period 2
Measure Participants	84	84
Mean (Standard Deviation) [Scores on a scale]	29.3 (15.02)	31.7 (14.89)

5. Secondary Outcome

Title	Subject Preference
Description	Subjects who completed both treatments were asked to indicate a preference for Treatment Period 1 or Treatment Period 2 or no preference. Preferences for a particular treatment period were mapped to the associated treatment and reported.
Time Frame	End of Study (week 11)

Outcome Measure Data

Analysis Population Description

Participants who completed both treatment periods

Arm/Group Title	Number of Participants Who Preferred IPX066	Number of Participants Who Preferred CLE	Number of Participants Who Had no Preference
Arm/Group Description	Participants who completed both treatment periods and who had a preference for IPX066	Participants who completed both treatment periods and who had a preference for CLE	Participants who completed both treatment periods and who did not indicate a preference for either treatment
Measure Participants	84	84	84
Count of Participants [Participants]	44 48.4%	23 NaN	17 NaN

Adverse Events

Arm/Group Title	Dose Conversion		IPX066		CLE (Active Comparator)		Washout
Arm/Group Description	Participants were to be converted from stable doses of CLE to open-label IPX066 over a 6-week period		Participants first received 2 weeks of IPX066 followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of CLE.		Participants first received 2 weeks of CLE followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of IPX066.		Participants receive open-label IPX066 for 1 week
All Cause Mortality
	Dose Conversion		IPX066		CLE (Active Comparator)		Washout
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dose Conversion		IPX066		CLE (Active Comparator)		Washout
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/91 (2.2%)		1/89 (1.1%)		0/88 (0%)		1/89 (1.1%)
Cardiac disorders
Atrial Fibrillation	1/91 (1.1%)	1	0/89 (0%)	0	0/88 (0%)	0	0/89 (0%)	0
Gastrointestinal disorders
Gastrointestinal Toxicity	1/91 (1.1%)	1	0/89 (0%)	0	0/88 (0%)	0	0/89 (0%)	0
Constipation	1/91 (1.1%)	1	0/89 (0%)	0	0/88 (0%)	0	0/89 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/91 (0%)	0	0/89 (0%)	0	0/88 (0%)	0	1/89 (1.1%)	1
Hypercalemia	1/91 (1.1%)	1	0/89 (0%)	0	0/88 (0%)	0	0/89 (0%)	0
Nervous system disorders
Sciatica	0/91 (0%)	0	1/89 (1.1%)	1	0/88 (0%)	0	0/89 (0%)	0
Other (Not Including Serious) Adverse Events
	Dose Conversion		IPX066		CLE (Active Comparator)		Washout
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/91 (15.4%)		13/89 (14.6%)		2/88 (2.3%)		1/89 (1.1%)
Gastrointestinal disorders
Nausea	6/91 (6.6%)	6	1/89 (1.1%)	1	0/88 (0%)	0	0/89 (0%)	0
Vomiting	2/91 (2.2%)	2	1/89 (1.1%)	1	0/88 (0%)	0	0/89 (0%)	0
Infections and infestations
Upper Respiratory Infection	2/91 (2.2%)	2	0/89 (0%)	0	0/88 (0%)	0	0/89 (0%)	0
Injury, poisoning and procedural complications
Fall	2/91 (2.2%)	2	1/89 (1.1%)	1	2/88 (2.3%)	2	0/89 (0%)	0
Nervous system disorders
Dyskinesia	1/91 (1.1%)	1	4/89 (4.5%)	4	0/88 (0%)	0	1/89 (1.1%)	1
Psychiatric disorders
Insomnia	1/91 (1.1%)	1	3/89 (3.4%)	3	0/88 (0%)	0	0/89 (0%)	0
Confusional State	0/91 (0%)	0	3/89 (3.4%)	3	0/88 (0%)	0	0/89 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.