An Extension of Istradefylline in North American Parkinson's Disease Patients Who Have Completed Study 6002-INT-001

• Sponsor: Kyowa Kirin, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00199381
• Collaborator: (none)
• Enrollment: 504
• Location: 1
• Arm: 1
• Duration (Months): 36
• Patients Per Site Per Month: 14

Study Details

Study Description

Brief Summary

This is an, open-label, long-term safety extension for patients in North America who have completed the prior istradefylline study 6002-INT-001.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Istradefylline	Phase 3

Detailed Description

Patients with Parkinson's disease with motor complications on levodopa therapy who completed the prior double-blind study 6002-INT-001 are eligible to enter into this long-term open safety study with a starting istradefylline dose of 20 or 40mg per day.

Study Design

• Study Type: Interventional
• Actual Enrollment: 504 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Multicenter Study of the Continued Safety of Istradefylline (KW-6002) In Subjects With Parkinson's Disease Who Have Recently Completed One Year of Treatment With Istradefylline.
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm Treatment with oral istradefylline (KW-6002) 20 or 40 mg once daily.	Drug: Istradefylline; Oral istradefylline (KW-6002) 20 or 40 mg once daily.; Other Names: KW-6002

Outcome Measures

Primary Outcome Measures

1. Safety as Measured by Adverse Events [Every 2 months up to 32 months]

   Investigation of the long-term tolerability and safety of istradefylline

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Completion of study 6002-INT-001

• Not of childbearing potential

Exclusion Criteria:

• Cancer within 5 years of enrollment

• ALT/AST levels > 2.5 times ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kyowa Pharmaceutical Inc.	Princeton	New Jersey	United States	08540

Sponsors and Collaborators

• Kyowa Kirin, Inc.

Investigators

• Study Director: Neil Sussman, MD, Kyowa Kirin, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00199381
• Other Study ID Numbers: 6002-US-025
• First Posted: Sep 20, 2005
• Last Update Posted: Nov 21, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by , ,: Parkinson's Disease; levodopa; end of dose wearing off; OFF time
• Additional relevant MeSH terms: Parkinson Disease; Istradefylline

Study Results

Participant Flow

Recruitment Details	73 study centers in the US and Canada recruited subjects from the initiation date (28 October 2005). Patients who had previously participated in Study 6002-INT-001 were eligible to participate in this follow-on safety study,and hence had been taking istradefylline for at least a year.
Pre-assignment Detail	Subjects completing 6002-INT-001 immediately before entering the study had an interruption of study drug of 30 days or less. Qualifying subjects with an interruption of more than 30 days had their baseline visit after laboratory tests results were reviewed by the Investigator.

Arm/Group Title	Single Arm
Arm/Group Description	Treatment with oral istradefylline (KW-6002) 20 or 40 mg once daily.
Period Title: Overall Study
STARTED	504
COMPLETED	0
NOT COMPLETED	504

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	Treatment with oral istradefylline (KW-6002) 20 or 40 mg once daily.
Overall Participants	503
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	244 48.5%
>=65 years	259 51.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (8.98)
Sex: Female, Male (Count of Participants)
Female	155 30.8%
Male	348 69.2%
Region of Enrollment (participants) [Number]
United States	401 79.7%
Canada	102 20.3%

Outcome Measures

1. Primary Outcome

Title	Safety as Measured by Adverse Events
Description	Investigation of the long-term tolerability and safety of istradefylline
Time Frame	Every 2 months up to 32 months

Outcome Measure Data

Analysis Population Description

Safety analysis set - all subjects who took at least one dose of study drug. 1 subject of the 504 enrolled did not take study drug and is not included in the safety analysis set.

Arm/Group Title	Single Arm
Arm/Group Description	Treatment with oral istradefylline (KW-6002) 20 or 40 mg once daily.
Measure Participants	503
Number [participants]	477 94.8%

Adverse Events

Time Frame	Dosing to end of treatment.
Arm/Group Title	Single Arm
Arm/Group Description	Treatment with oral istradefylline (KW-6002) 20 or 40 mg once daily.
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	201/503 (40%)
Blood and lymphatic system disorders
Anaemia	2/503 (0.4%)	4
Cardiac disorders
Myocardial infarction	6/503 (1.2%)	6
Coronary artery disease	5/503 (1%)	5
Atrial fibrillation	3/503 (0.6%)	3
Cardiac failure congestive	3/503 (0.6%)	4
Acute myocardial infarction	1/503 (0.2%)	1
Angina pectoris	1/503 (0.2%)	1
Atrioventricular block	1/503 (0.2%)	1
Atrioventricular block complete	1/503 (0.2%)	1
Bradycardia	1/503 (0.2%)	1
Cardiac arrest	1/503 (0.2%)	1
Cardio-respiratory arrest	1/503 (0.2%)	1
Cardiomegaly	1/503 (0.2%)	1
Sinus arrest	1/503 (0.2%)	1
Ventricular tachycardia	1/503 (0.2%)	1
Ear and labyrinth disorders
Vertigo	2/503 (0.4%)	2
Eye disorders
Retinal detachment	1/503 (0.2%)	1
Gastrointestinal disorders
Abdominal hernia	2/503 (0.4%)	2
Constipation	2/503 (0.4%)	3
Diarrhoea	2/503 (0.4%)	2
Inguinal hernia	2/503 (0.4%)	2
Intestinal obstruction	2/503 (0.4%)	2
Abdominal pain upper	1/503 (0.2%)	1
Abdominal strangulated hernia	1/503 (0.2%)	1
Coeliac disease	1/503 (0.2%)	1
Colonic polyp	1/503 (0.2%)	1
Diverticulum	1/503 (0.2%)	1
Dysphagia	1/503 (0.2%)	1
Gastrointestinal haemorrhage	1/503 (0.2%)	1
Ileus	1/503 (0.2%)	2
Mallory-Weiss syndrome	1/503 (0.2%)	1
Nausea	1/503 (0.2%)	1
Upper gastrointestinal haemorrhage	1/503 (0.2%)	1
General disorders
Asthenia	3/503 (0.6%)	3
Chest pain	2/503 (0.4%)	2
Pyrexia	2/503 (0.4%)	2
Death	1/503 (0.2%)	1
Drug interaction	1/503 (0.2%)	1
Gait abnormal	1/503 (0.2%)	1
Generalised oedema	1/503 (0.2%)	1
Injection site haemorrhage	1/503 (0.2%)	1
Non-cardiac chest pain	1/503 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	1/503 (0.2%)	1
Gangrenous cholecystitis	1/503 (0.2%)	1
Infections and infestations
Pneumonia	8/503 (1.6%)	8
Cellulitis	4/503 (0.8%)	4
Urinary tract infection	4/503 (0.8%)	5
Postoperative infection	2/503 (0.4%)	2
Urosepsis	2/503 (0.4%)	2
Abscess jaw	1/503 (0.2%)	1
Abscess limb	1/503 (0.2%)	1
Bronchitis	1/503 (0.2%)	1
Bronchopneumonia	1/503 (0.2%)	1
Diverticultis	1/503 (0.2%)	1
Gastroenteritis	1/503 (0.2%)	1
Infected skin ulcer	1/503 (0.2%)	1
Infection	1/503 (0.2%)	1
Labyrinthitis	1/503 (0.2%)	1
Lobar pneumonia	1/503 (0.2%)	1
Localised infection	1/503 (0.2%)	1
Pneumonia staphylococcal	1/503 (0.2%)	1
Sepsis	1/503 (0.2%)	1
Staphylococcal sepsis	1/503 (0.2%)	1
Viral infection	1/503 (0.2%)	1
Injury, poisoning and procedural complications
Accident	9/503 (1.8%)	9
Hip fracture	8/503 (1.6%)	8
Femoral neck fracture	3/503 (0.6%)	3
Cervical vertebral fracture	2/503 (0.4%)	2
Clavicle fracture	2/503 (0.4%)	2
Accidental overdose	1/503 (0.2%)	1
Acetabulum fracture	1/503 (0.2%)	1
Ankle fracture	1/503 (0.2%)	1
Caustic injury	1/503 (0.2%)	1
Closed head injury	1/503 (0.2%)	1
Comminuted fracture	1/503 (0.2%)	1
Concussion	1/503 (0.2%)	1
Facial bones fracture	1/503 (0.2%)	1
Humerus fracture	1/503 (0.2%)	1
Injury	1/503 (0.2%)	1
Joint dislocation	1/503 (0.2%)	1
Ligament injury	1/503 (0.2%)	1
Muscle rupture	1/503 (0.2%)	1
Patella fracture	1/503 (0.2%)	1
Pneumothorax traumatic	1/503 (0.2%)	1
Postoperative ileus	1/503 (0.2%)	1
Rib fracture	1/503 (0.2%)	1
Skin laceration	1/503 (0.2%)	1
Tendon rupture	1/503 (0.2%)	1
Wound dehiscence	1/503 (0.2%)	1
Investigations
Weight decreased	1/503 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	2/503 (0.4%)	3
Musculoskeletal and connective tissue disorders
Localised osteoarthritis	6/503 (1.2%)	6
Osteoarthritis	6/503 (1.2%)	6
Cervical spinal stenosis	5/503 (1%)	5
Spinal column stenosis	5/503 (1%)	7
Arthralgia	3/503 (0.6%)	3
Intervertebral disc protrusion	3/503 (0.6%)	4
Spondylosis	3/503 (0.6%)	3
Bursitis	2/503 (0.4%)	2
Lumbar spinal stenosis	2/503 (0.4%)	2
Arthritis	1/503 (0.2%)	1
Kyphoscoliosis	1/503 (0.2%)	1
Muscle spasms	1/503 (0.2%)	1
Neck pain	1/503 (0.2%)	1
Pain in extemity	1/503 (0.2%)	2
Rhabdomyolysis	1/503 (0.2%)	1
Rotator cuff syndrome	1/503 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	4/503 (0.8%)	4
Squamous cell carcinoma of skin	3/503 (0.6%)	3
Bladder cancer	1/503 (0.2%)	1
Cyst	1/503 (0.2%)	1
Oesophageal carcinoma	1/503 (0.2%)	1
Nervous system disorders
Parkinson's disease	51/503 (10.1%)	55
Syncope	8/503 (1.6%)	8
Cerebrovascular accident	4/503 (0.8%)	4
Transient ischaemic attack	4/503 (0.8%)	4
Convulsion	3/503 (0.6%)	3
Lightheadedness	2/503 (0.4%)	2
Somnolence	2/503 (0.4%)	2
Spinal cord compression	2/503 (0.4%)	3
Cerebral infarction	1/503 (0.2%)	1
Cervical myelopathy	1/503 (0.2%)	1
Cervicobrachial syndrome	1/503 (0.2%)	1
Dementia	1/503 (0.2%)	1
Dizziness	1/503 (0.2%)	1
Dyskinesia	1/503 (0.2%)	1
Haemorrhage intracranial	1/503 (0.2%)	1
Headache	1/503 (0.2%)	1
Hypoaesthesia	1/503 (0.2%)	1
Ischaemic stroke	1/503 (0.2%)	1
Metabolic encephalopathy	1/503 (0.2%)	2
Myasthenia gravis	1/503 (0.2%)	1
Myelopathy	1/503 (0.2%)	1
Paraparesis	1/503 (0.2%)	1
Radiculitis lumbosacral	1/503 (0.2%)	1
Tremor	1/503 (0.2%)	1
Psychiatric disorders
Confusional state	10/503 (2%)	11
Psychotic disorder	5/503 (1%)	5
Delirium	4/503 (0.8%)	4
Hallucination	3/503 (0.6%)	3
Agitation	1/503 (0.2%)	1
Delusion	1/503 (0.2%)	1
Depression	1/503 (0.2%)	1
Hallucination, visual	1/503 (0.2%)	1
Markedly reduced dietary intake	1/503 (0.2%)	1
Renal and urinary disorders
Haematuria	1/503 (0.2%)	1
Pollakiuria	1/503 (0.2%)	1
Renal failure acute	1/503 (0.2%)	1
Renal insufficiency	1/503 (0.2%)	1
Urinary retention	1/503 (0.2%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	4/503 (0.8%)	4
Colpocele	1/503 (0.2%)	1
Dysmenorrhoea	1/503 (0.2%)	1
Prostatic disorder	1/503 (0.2%)	1
Urogenital prolapse	1/503 (0.2%)	2
Uterine prolapse	1/503 (0.2%)	1
Uterovaginal prolapse	1/503 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	4/503 (0.8%)	4
Dyspnoea	3/503 (0.6%)	4
Pneumonia aspiration	3/503 (0.6%)	3
Respiratory failure	3/503 (0.6%)	3
Respiratory distress	2/503 (0.4%)	2
Acute respiratory distress snydrome	1/503 (0.2%)	1
Dyspnoea exertional	1/503 (0.2%)	1
Pulmonary oedema	1/503 (0.2%)	1
Surgical and medical procedures
Cardiac pacemaker revision	1/503 (0.2%)	1
Medical device removal	1/503 (0.2%)	1
Vascular disorders
Deep vein thrombosis	2/503 (0.4%)	2
Hypotension	2/503 (0.4%)	2
Vascular pseudoaneurysm	2/503 (0.4%)	2
Hypertension	1/503 (0.2%)	1
Malignant hypertension	1/503 (0.2%)	1
Orthostatic hypotension	1/503 (0.2%)	1
Peripheral vascular disorder	1/503 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	276/503 (54.9%)
Cardiac disorders
Oedema peripheral	41/503 (8.2%)
Gastrointestinal disorders
Constipation	49/503 (9.7%)
General disorders
Nausea	27/503 (5.4%)
Asthenia	29/503 (5.8%)
Fatigue	25/503 (5%)
Infections and infestations
Nasopharyngitis	29/503 (5.8%)
Upper respiratory tract infection	36/503 (7.2%)
Urinary tract infection	47/503 (9.3%)
Injury, poisoning and procedural complications
Accident	102/503 (20.3%)
Investigations
Weight decreased	35/503 (7%)
Musculoskeletal and connective tissue disorders
Arthralgia	63/503 (12.5%)
Back pain	46/503 (9.1%)
Pain in extremity	36/503 (7.2%)
Nervous system disorders
Parkinson's disease	151/503 (30%)
Balance disorder	38/503 (7.6%)
Dyskinesia	136/503 (27%)
Freezing phenomenon	32/503 (6.4%)
Lightheadedness	33/503 (6.6%)
Headache	26/503 (5.2%)
Tremor	35/503 (7%)
Psychiatric disorders
Anxiety	40/503 (8%)
Confusional state	29/503 (5.8%)
Depression	54/503 (10.7%)
Hallucination	69/503 (13.7%)
Insomnia	49/503 (9.7%)

Limitations/Caveats

The Sponsor decided to terminate the study early (not for safety reasons); as a result 323 subjects discontinued early. Mean duration of therapy was 18.7 months (0.4 to 31.4 months); median duration was 21.0 months. Total exposure 767 subject years.

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.