A Study To Evaluate The Safety And Efficacy Of IPX066 In Advanced Parkinson's Disease (ADVANCE-PD).

• Sponsor: Impax Laboratories, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00974974
• Collaborator: (none)
• Enrollment: 471
• Locations: 73
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a study to evaluate the safety and efficacy of IPX066 in advanced Parkinson's disease.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: IPX066; Drug: IR CD-LD	Phase 3

Detailed Description

A randomized, double-blind, active-control, parallel-group 13-week comparison of IPX066 versus regular carbidopa-levodopa (CD-LD). Prior to randomization, subjects on a stable regular LD regimen will enter a 3-week dose-adjustment period for IR CD-LD, followed by a 6-week dose-conversion period to IPX066.

Study Design

• Study Type: Interventional
• Actual Enrollment: 471 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Study To Evaluate The Safety And Efficacy Of IPX066 In Advanced Parkinson's Disease
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IPX066 Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Drug: IPX066; extended-release carbidopa-levodopa capsules; Other Names: ER CD-LD ; Drug: IR CD-LD; immediate-release carbidopa-levodopa tablets; Other Names: immediate-release carbidopa-levodopa
Active Comparator: IR CD-LD Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).	Drug: IPX066; extended-release carbidopa-levodopa capsules; Other Names: ER CD-LD ; Drug: IR CD-LD; immediate-release carbidopa-levodopa tablets; Other Names: immediate-release carbidopa-levodopa

Outcome Measures

Primary Outcome Measures

1. Percentage of "Off" Time During Waking Hours at End of Study [22 weeks]

   Percentage of "off" time during waking hours at end of study is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."

Secondary Outcome Measures

1. "Off" Time [22 weeks]

   "Off" time hours is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."

2. "On" Time Without Troublesome Dyskinesia [22 weeks]

   "On" time without troublesome dyskinesiais measured by using the Parkinson's disease diary. "On" time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living."

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 PD.

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

3. Currently being treated with IR LD (CD-LD or benserazide-LD) and on a stable regimen of IR LD for at least 4 weeks and:

• Requiring a total daily IR LD dose of at least 400 mg

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

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 or planning to take during participation in the clinical study: any controlled-release LD product, additional CD (e.g., Lodosyn®) or benserazide (e.g. Serazide®), catechol-O-methyl transferase inhibitors (e.g., entacapone and tolcapone), nonselective MAO inhibitors, apomorphine, and antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder.

5. Allergic to Yellow Dye #5 (tartrazine).

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. A 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 and/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	Investigator 17	Birmingham	Alabama	United States	35233
2	Investigator 49	Phoenix	Arizona	United States	85013
3	Investigator 7	Little Rock	Arkansas	United States	72205
4	Investigator 3	La Jolla	California	United States	92037
5	Investigator 31	Sunnyvale	California	United States	94085
6	Investigator 6	Torrance	California	United States	90502
7	Investigator 51	Aurora	Colorado	United States	80045
8	Investigator 10	New Haven	Connecticut	United States	06510
9	Investigator 64	Bradenton	Florida	United States	34205
10	Investigator 61	Hollywood	Florida	United States	33021
11	Investigator 5	Ocala	Florida	United States	34471
12	Investigator 15	Port Charlotte	Florida	United States	33980
13	Investigator 8	Port Charlotte	Florida	United States	33980
14	Investigator 4	Saint Petersburg	Florida	United States	33713
15	Investigator 46	Augusta	Georgia	United States	30912
16	Investigator 38	Boise	Idaho	United States	83702
17	Investigator 19	Chicago	Illinois	United States	60611
18	Investigator 40	Chicago	Illinois	United States	60612
19	Investigator 39	Des Moines	Iowa	United States	50309
20	Investigator 29	Kansas City	Kansas	United States	66160
21	Investigator 1	Bingham Farms	Michigan	United States	48025
22	Investigator 21	New Brunswick	New Jersey	United States	08901
23	Investigator 25	Albany	New York	United States	12208
24	Investigator 8	Commack	New York	United States	11725
25	Investigator 12	New York	New York	United States	10032
26	Investigator 11	Durham	North Carolina	United States	27707
27	Investigator 9	Raleigh	North Carolina	United States	27607
28	Investigator 20	Cincinnati	Ohio	United States	45219
29	Investigator 42	Toledo	Ohio	United States	43614
30	Investigator 60	Tulsa	Oklahoma	United States	74137
31	Investigator 14	Charleston	South Carolina	United States	29401
32	Investigator 16	Dallas	Texas	United States	75390-9016
33	Investigator 13	Houston	Texas	United States	77030-2744
34	Investigator 65	Tacoma	Washington	United States	98405
35	Investigator 2	Milwaukee	Wisconsin	United States	53233
36	Investigator 24	London	Ontario	Canada	N6A 5A5
37	Investigator 18	Ottawa	Ontario	Canada	K1G 4G3
38	Investigator 26	Quebec		Canada	G1R 3X5
39	Investigator 32	Strasbourg Cedex	Alsace	France	67091
40	Investigator 22	Dijon	Bourgogne	France	21000
41	Investigator 58	Paris	Ile-de-france	France	75013
42	Investigator 33	Toulouse	Midi-pyrenees	France	31059
43	Investigator 52	Lille	NORD Pas-de-calais	France	59037
44	Investigator 30	Sachsen	Dresden	Germany	1307
45	Investigator 27	Westerstede	Niedersachsen	Germany	26655
46	Investigator 23	Berlin		Germany	10437
47	Investigator 72	Berlin		Germany	12163
48	Investigator 28	Berlin		Germany	13088
49	Investigator 67	Berlin		Germany	13353
50	Investigator 48	Bydgoszcz	Kujawsko-pomorskie	Poland	85-796
51	Investigator 59	Lublin	Lubelskie	Poland	20-718
52	Investigator 37	Kraków	Malopolskie	Poland	31-530
53	Investigator 36	Warszawa	Mazowieckie	Poland	02-777
54	Investigator 35	Mosina	Wielkopoloskie	Poland	62-050
55	Investigator 54	Szczecin	Zachodniopomorskie	Poland	70-215
56	Investigator 34	Katowice		Poland	40-546
57	Investigator 69	Târgu-Mureş	Mures	Romania	540136
58	Investigator 68	Brasov		Romania	500283
59	Investigator 62	Bucuresti		Romania	20125
60	Investigator 63	Târgu Mureş		Romania	540136
61	Investigator 43	Terrassa	Barcelona	Spain	8221
62	Investigator 70	Barcelona		Spain	8028
63	Investigator 57	Barcelona		Spain	8036
64	Investigator 45	Barcelona		Spain	8190
65	Investigator 50	Madrid		Spain	28006
66	Investigator 53	Madrid		Spain	28922
67	Investigator 55	Dnepropetrovsk	Dnipropetrovsk	Ukraine	49005
68	Investigator 56	Vinnitsa	Vinnytsya	Ukraine	21005
69	Investigator 47	Zaporozhye	Zaporizhzhya	Ukraine	69600
70	Investigator 71	Donetsk		Ukraine	83003
71	Investigator 44	Kharkiv		Ukraine	61068
72	Investigator 66	Odessa		Ukraine	65117
73	Investigator 41	Zaporozhye		Ukraine	69035

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: NCT00974974
• Other Study ID Numbers: IPX066-B09-02
• First Posted: Sep 11, 2009
• Last Update Posted: Aug 11, 2020
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Impax Laboratories, LLC: Parkinson's Disease
• Additional relevant MeSH terms: Parkinson Disease; Levodopa; Carbidopa; Carbidopa, levodopa drug combination

Study Results

Participant Flow

Recruitment Details	Study period was form September 29, 2009 to January 19, 2011.
Pre-assignment Detail	Prior to randomization, subjects needed to complete a 3-week dose adjustment of IR CD-LD followed by 6-week dose conversion to IPX066.

Arm/Group Title	IPX066	IR CD-LD (Active Comparator)
Arm/Group Description	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).
Period Title: IR CD-LD Dose Adjustment
STARTED	0	471
COMPLETED	0	450
NOT COMPLETED	0	21
Period Title: IR CD-LD Dose Adjustment
STARTED	450	0
COMPLETED	393	0
NOT COMPLETED	57	0
Period Title: IR CD-LD Dose Adjustment
STARTED	201	192
COMPLETED	186	182
NOT COMPLETED	15	10

Baseline Characteristics

Arm/Group Title	IPX066	Carbidopa-Levodopa	Total
Arm/Group Description	Investigational product IPX066	Immediate-release carbidopa and levodopa	Total of all reporting groups
Overall Participants	201	192	393
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (10.0)	63.4 (8.8)	63.2 (9.4)
Sex: Female, Male (Count of Participants)
Female	72 35.8%	67 34.9%	139 35.4%
Male	129 64.2%	125 65.1%	254 64.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 1.5%	8 4.2%	11 2.8%
Not Hispanic or Latino	192 95.5%	182 94.8%	374 95.2%
Unknown or Not Reported	6 3%	2 1%	8 2%
Race/Ethnicity, Customized (participants) [Number]
White	196 97.5%	186 96.9%	382 97.2%
Black or African American	2 1%	1 0.5%	3 0.8%
Asian	1 0.5%	1 0.5%	2 0.5%
American Indian or Alaskan Native	0 0%	2 1%	2 0.5%
Other	1 0.5%	2 1%	3 0.8%
Unknown	1 0.5%	0 0%	1 0.3%
Region of Enrollment (participants) [Number]
Canada	10 5%	8 4.2%	18 4.6%
Romania	3 1.5%	4 2.1%	7 1.8%
United States	98 48.8%	93 48.4%	191 48.6%
Ukraine	37 18.4%	38 19.8%	75 19.1%
Poland	34 16.9%	33 17.2%	67 17%
France	2 1%	1 0.5%	3 0.8%
Germany	12 6%	11 5.7%	23 5.9%
Spain	5 2.5%	4 2.1%	9 2.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of "Off" Time During Waking Hours at End of Study
Description	Percentage of "off" time during waking hours at end of study is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."
Time Frame	22 weeks

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	IPX066	IR CD-LD (Active Comparator)
Arm/Group Description	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).
Measure Participants	201	192
Mean (Standard Deviation) [percentage]	23.82 (14.91)	29.79 (15.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IR CD-LD (Active Comparator)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	"Off" Time
Description	"Off" time hours is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."
Time Frame	22 weeks

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	IPX066	IR CD-LD (Active Comparator)
Arm/Group Description	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).
Measure Participants	201	192
Mean (Standard Deviation) [hours]	3.87 (2.46)	4.88 (2.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IR CD-LD (Active Comparator)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	"On" Time Without Troublesome Dyskinesia
Description	"On" time without troublesome dyskinesiais measured by using the Parkinson's disease diary. "On" time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living."
Time Frame	22 weeks

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	IPX066	IR CD-LD (Active Comparator)
Arm/Group Description	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).
Measure Participants	201	192
Mean (Standard Deviation) [hours]	11.84 (2.96)	10.91 (2.82)

Adverse Events

Time Frame	22 weeks
Arm/Group Title	IPX066		Carbidopa-Levodopa
Arm/Group Description	Investigational product IPX066		Immediate-release carbidopa and levodopa
All Cause Mortality
	IPX066		Carbidopa-Levodopa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IPX066		Carbidopa-Levodopa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/201 (5.5%)		5/192 (2.6%)
Cardiac disorders
Acute Myocardial Infarction	1/201 (0.5%)		0/192 (0%)
Atrial Fibrillation	0/201 (0%)		1/192 (0.5%)
Gastrointestinal disorders
Small Intestinal Obstruction	1/201 (0.5%)		0/192 (0%)
Volvulus	1/201 (0.5%)		0/192 (0%)
General disorders
Chest Pain	0/201 (0%)		1/192 (0.5%)
Non-cardiac Chest Pain	1/201 (0.5%)		0/192 (0%)
Infections and infestations
Osteomyelitis	0/201 (0%)		1/192 (0.5%)
Pneumonia	0/201 (0%)		1/192 (0.5%)
Injury, poisoning and procedural complications
Subdural Hematoma	0/201 (0%)		1/192 (0.5%)
Musculoskeletal and connective tissue disorders
Arthritis	1/201 (0.5%)		0/192 (0%)
Intervertebral Disc Degeneration	0/201 (0%)		1/192 (0.5%)
Spondylolisthesis	1/201 (0.5%)		0/192 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic Lymphocytic Leukaemia	1/201 (0.5%)		0/192 (0%)
Neuroendocrine Carcinoma of the Skin	1/201 (0.5%)		0/192 (0%)
Nervous system disorders
Cerebral Infarction	1/201 (0.5%)		0/192 (0%)
Transient Ischaemic Attack	1/201 (0.5%)		0/192 (0%)
Psychiatric disorders
Acute Psychosis	1/201 (0.5%)		0/192 (0%)
Anxiety	1/201 (0.5%)		0/192 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	0/201 (0%)		1/192 (0.5%)
Surgical and medical procedures
Toe Amputation	0/201 (0%)		1/192 (0.5%)
Vascular disorders
Deep Vein Thrombosis	1/201 (0.5%)		0/192 (0%)
Other (Not Including Serious) Adverse Events
	IPX066		Carbidopa-Levodopa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/201 (28.4%)		50/192 (26%)
Gastrointestinal disorders
nausea	6/201 (3%)		3/192 (1.6%)
Diarrhoea	4/201 (2%)		1/192 (0.5%)
Constipation	2/201 (1%)		2/192 (1%)
Vomiting	1/201 (0.5%)		4/192 (2.1%)
General disorders
Oedema Peripheral	4/201 (2%)		4/192 (2.1%)
Gait Disturbance	0/201 (0%)		3/192 (1.6%)
Infections and infestations
Upper Respiratory Tract Infection	4/201 (2%)		4/192 (2.1%)
Urinary Tract Infection	4/201 (2%)		4/192 (2.1%)
Bronchitis	3/201 (1.5%)		2/192 (1%)
Nasopharyngitis	1/201 (0.5%)		3/192 (1.6%)
Injury, poisoning and procedural complications
Fall	6/201 (3%)		4/192 (2.1%)
Arthropod Bite	0/201 (0%)		2/192 (1%)
Skin Laceration	0/201 (0%)		2/192 (1%)
Investigations
Weight Decreased	4/201 (2%)		0/192 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	3/201 (1.5%)		4/192 (2.1%)
Arthralgia	2/201 (1%)		4/192 (2.1%)
Muscle Spasms	1/201 (0.5%)		3/192 (1.6%)
Nervous system disorders
Dizziness	5/201 (2.5%)		2/192 (1%)
Dyskinesia	5/201 (2.5%)		2/192 (1%)
Headache	2/201 (1%)		3/192 (1.6%)
On and Off Phenomenon	2/201 (1%)		2/192 (1%)
Psychiatric disorders
Insomnia	7/201 (3.5%)		2/192 (1%)
Sleep Disorder	4/201 (2%)		4/192 (2.1%)
Anxiety	2/201 (1%)		3/192 (1.6%)
Depression	1/201 (0.5%)		5/192 (2.6%)
Skin and subcutaneous tissue disorders
Rash	0/201 (0%)		3/192 (1.6%)
Vascular disorders
Orthostatic Hypotension	2/201 (1%)		2/192 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publication of the results of the Study conducted at the Site shall not be made before the first multi-site publication by Sponsor.