Trial Outcomes & Findings for Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy (NCT NCT00099268)

Last Updated: 2012-04-23

Results Overview

Dyskinesia was assessed by a blinded rater at each visit. Time to dyskinesia was defined as the visit at which the rater first answered "yes" to the following question: "In your opinion, does this patient have dyskinesia?" Time to dyskinesia was estimated by Kaplan-Meier product limit estimate that takes into consideration patients who did not experience dyskinesia by censoring them at the end of the study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

747 participants

Primary outcome timeframe

Treatment duration for an individual patient varied between a minimum of 134 weeks for those patients recruited last and a maximum of 208 weeks for those patients recruited first

Results posted on

2012-04-23

Participant Flow

Participant milestones

Participant milestones
Measure	Carbidopa/Levodopa/Entacapone Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Overall Study STARTED	374	373
Overall Study Intent-to-Treat	373	372
Overall Study COMPLETED	282	291
Overall Study NOT COMPLETED	92	82

Reasons for withdrawal

Reasons for withdrawal
Measure	Carbidopa/Levodopa/Entacapone Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Overall Study Withdrawal by Subject	46	28
Overall Study Adverse Event	19	19
Overall Study Protocol Violation	9	8
Overall Study Lost to Follow-up	6	4
Overall Study Lack of Efficacy	5	18
Overall Study Administrative problems	4	4
Overall Study Death	3	1

Baseline Characteristics

Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carbidopa/Levodopa/Entacapone n=373 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=372 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Total n=745 Participants Total of all reporting groups
Age Continuous	60.6 years STANDARD_DEVIATION 8.67 • n=5 Participants	59.8 years STANDARD_DEVIATION 8.20 • n=7 Participants	60.2 years STANDARD_DEVIATION 8.44 • n=5 Participants
Sex: Female, Male Female	128 Participants n=5 Participants	150 Participants n=7 Participants	278 Participants n=5 Participants
Sex: Female, Male Male	245 Participants n=5 Participants	222 Participants n=7 Participants	467 Participants n=5 Participants

PRIMARY outcome

Timeframe: Treatment duration for an individual patient varied between a minimum of 134 weeks for those patients recruited last and a maximum of 208 weeks for those patients recruited first

Population: The intent to treat (ITT) population consisted of all patients randomized who received at least one dose of study drug. Following the ITT principle, patients were analyzed according to the treatment they were assigned at randomization.

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=373 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=372 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Time to First Occurrence of Dyskinesia	90.7 weeks 95% Confidence Interval 47.9 • Interval 65.3 to 104.0	117.1 weeks 95% Confidence Interval 51.5 • Interval 92.1 to 132.6

SECONDARY outcome

Timeframe: Baseline, Week 6 and Week 130

The UPDRS is a standardized assessment scale used to measure the patient's disease state. It was to be completed by a blinded rater. There are 6 parts to the UPDRS. Part II (items 5-17; total score 0-52 units on the scale) measures the patient's activities of daily living and part III (items 18-31; total score 0-56 units on the scale) measures the motor function of the patient. The total score ranges from 0 to 108 units on the scale. A higher score indicates greater disability. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=373 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=372 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score (Parts II and III) Change from baseline to Week 6	21.9 Units on a scale Standard Deviation 11.96	21.8 Units on a scale Standard Deviation 11.24
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score (Parts II and III) Change from baseline to Week 130	23.2 Units on a scale Standard Deviation 13.38	22.8 Units on a scale Standard Deviation 13.21

SECONDARY outcome

Timeframe: Baseline to Week 134

Wearing-off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient as to whether he/she had noticed that the benefits of the study drug were wearing-off.

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=305 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=333 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Occurrence of Wearing-off	139 Participants 45.6	161 Participants 48.3

SECONDARY outcome

Timeframe: Baseline to end of study (134-208 weeks of treatment)

Wearing off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient whether he/she had noticed that the benefits of the study drug wear-off. A motor complications and patient questionnaire card were provided to assist the blinded rater in determining whether a patient had experienced wearing-off.

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=373 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=372 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Time to First Occurrence of Wearing-off	131.7 Weeks Standard Error 3.8	129.5 Weeks Standard Error 3.6

SECONDARY outcome

Timeframe: Baseline to Week 208

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=307 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=318 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Occurrence of Dyskinesia	128 Participants 41.7	103 Participants 32.4

SECONDARY outcome

Timeframe: Baseline to Week 156

The PDQ-39 instrument is used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The total score can range from 39 to 190. A lower score indicates better quality of life. A negative change score indicates an improvement.

Outcome measures

Outcome measures
Measure	Carbidopa/Levodopa/Entacapone n=201 Participants Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=213 Participants Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Change From Baseline in Health-related Quality of Life Assessed Using the 39-item Parkinson's Disease Questionnaire (PDQ-39)	4.1 Units on a scale Standard Deviation 12.06	1.8 Units on a scale Standard Deviation 11.79

Adverse Events

Carbidopa/Levodopa/Entacapone

Serious events: 91 serious events

Other events: 310 other events

Deaths: 0 deaths

Carbidopa/Levodopa

Serious events: 84 serious events

Other events: 291 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Carbidopa/Levodopa/Entacapone n=373 participants at risk Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=371 participants at risk Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Blood and lymphatic system disorders Lymphocytosis	0.27% 1/373	0.00% 0/371
Cardiac disorders Acute myocardial infarction	0.27% 1/373	0.00% 0/371
Cardiac disorders Angina pectoris	0.54% 2/373	1.3% 5/371
Cardiac disorders Angina unstable	0.27% 1/373	0.27% 1/371
Cardiac disorders Aortic valve stenosis	0.00% 0/373	0.27% 1/371
Cardiac disorders Atrial fibrillation	0.54% 2/373	0.27% 1/371
Cardiac disorders Atrial flutter	0.27% 1/373	0.00% 0/371
Cardiac disorders Bradycardia	0.00% 0/373	0.27% 1/371
Cardiac disorders Cardiac arrest	0.27% 1/373	0.00% 0/371
Cardiac disorders Cardiac failure	0.00% 0/373	0.27% 1/371
Cardiac disorders Cardiac failure congestive	0.54% 2/373	0.00% 0/371
Cardiac disorders Cardiac flutter	0.27% 1/373	0.00% 0/371
Cardiac disorders Coronary artery disease	0.54% 2/373	0.54% 2/371
Cardiac disorders Coronary artery stenosis	0.27% 1/373	0.54% 2/371
Cardiac disorders Myocardial infarction	1.3% 5/373	0.00% 0/371
Cardiac disorders Palpitations	0.27% 1/373	0.00% 0/371
Cardiac disorders Supraventricular tachycardia	0.00% 0/373	0.27% 1/371
Cardiac disorders Ventricular tachycardia	0.00% 0/373	0.27% 1/371
Congenital, familial and genetic disorders Muscular dystrophy	0.27% 1/373	0.00% 0/371
Congenital, familial and genetic disorders Vitello-intestinal duct remnant	0.00% 0/373	0.27% 1/371
Ear and labyrinth disorders Vertigo	0.00% 0/373	0.27% 1/371
Eye disorders Chalazion	0.27% 1/373	0.00% 0/371
Eye disorders Eyelid ptosis	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Abdominal adhesions	0.27% 1/373	0.27% 1/371
Gastrointestinal disorders Abdominal discomfort	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Anal fissure	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Colitis ulcerative	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Colonic obstruction	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Constipation	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Diarrhoea	0.54% 2/373	0.00% 0/371
Gastrointestinal disorders Flatulence	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Gastric ulcer perforation	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Gastrooesophageal reflux disease	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Hiatus hernia	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Inguinal hernia	0.80% 3/373	0.54% 2/371
Gastrointestinal disorders Intestinal ischaemia	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Intestinal obstruction	0.54% 2/373	0.00% 0/371
Gastrointestinal disorders Nausea	0.00% 0/373	0.81% 3/371
Gastrointestinal disorders Pancreatitis	0.27% 1/373	0.00% 0/371
Gastrointestinal disorders Peritonitis	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/373	0.27% 1/371
Gastrointestinal disorders Vomiting	0.00% 0/373	0.27% 1/371
General disorders Chest discomfort	0.54% 2/373	0.27% 1/371
General disorders Chest pain	0.00% 0/373	0.54% 2/371
General disorders General physical health deterioration	0.27% 1/373	0.00% 0/371
General disorders Non-cardiac chest pain	0.00% 0/373	0.27% 1/371
General disorders Oedema peripheral	0.00% 0/373	0.27% 1/371
General disorders Orthostatic intolerance	0.00% 0/373	0.27% 1/371
Hepatobiliary disorders Cholelithiasis	0.54% 2/373	0.00% 0/371
Infections and infestations Acute sinusitis	0.00% 0/373	0.27% 1/371
Infections and infestations Appendicitis	0.27% 1/373	0.27% 1/371
Infections and infestations Arthritis bacterial	0.00% 0/373	0.27% 1/371
Infections and infestations Bronchitis	0.27% 1/373	0.27% 1/371
Infections and infestations Bursitis infective	0.27% 1/373	0.00% 0/371
Infections and infestations Campylobacter gastroenteritis	0.27% 1/373	0.00% 0/371
Infections and infestations Erysipelas	0.27% 1/373	0.00% 0/371
Infections and infestations Gastroenteritis	0.27% 1/373	0.27% 1/371
Infections and infestations Gastroenteritis viral	0.00% 0/373	0.27% 1/371
Infections and infestations Herpes zoster	0.27% 1/373	0.00% 0/371
Infections and infestations Lobar pneumonia	0.00% 0/373	0.27% 1/371
Infections and infestations Pneumonia	0.54% 2/373	0.00% 0/371
Infections and infestations Pneumonia pneumococcal	0.27% 1/373	0.00% 0/371
Infections and infestations Postoperative wound infection	0.27% 1/373	0.27% 1/371
Infections and infestations Urinary tract infection	0.27% 1/373	0.00% 0/371
Infections and infestations Viral infection	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Accident at work	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Anaesthetic complication	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Ankle fracture	0.54% 2/373	0.00% 0/371
Injury, poisoning and procedural complications Back injury	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Clavicle fracture	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Drug administration error	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Fall	1.9% 7/373	1.9% 7/371
Injury, poisoning and procedural complications Femoral neck fracture	0.27% 1/373	0.27% 1/371
Injury, poisoning and procedural complications Fractured sacrum	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Hip fracture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Joint sprain	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Limb traumatic amputation	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Medical device complication	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Meniscus lesion	0.54% 2/373	0.27% 1/371
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Pelvic fracture	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Post procedural haemorrhage	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Postoperative fever	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Rib fracture	0.27% 1/373	0.00% 0/371
Injury, poisoning and procedural complications Road traffic accident	0.54% 2/373	0.54% 2/371
Injury, poisoning and procedural complications Scrotal haematoma	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Spinal fracture	0.27% 1/373	0.54% 2/371
Injury, poisoning and procedural complications Stress fracture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Thermal burn	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Traumatic brain injury	0.00% 0/373	0.27% 1/371
Injury, poisoning and procedural complications Wrist fracture	0.54% 2/373	0.00% 0/371
Investigations Weight decreased	0.27% 1/373	0.00% 0/371
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Arthralgia	0.27% 1/373	0.81% 3/371
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/373	0.81% 3/371
Musculoskeletal and connective tissue disorders Bursa calcification	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Compartment syndrome	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.27% 1/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.1% 4/373	1.3% 5/371
Musculoskeletal and connective tissue disorders Intervertebral disc space narrowing	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Mobility decreased	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Osteoarthritis	1.3% 5/373	0.54% 2/371
Musculoskeletal and connective tissue disorders Osteonecrosis	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Pain in extremity	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.27% 1/373	0.27% 1/371
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.27% 1/373	0.00% 0/371
Musculoskeletal and connective tissue disorders Synovial cyst	0.27% 1/373	0.54% 2/371
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.6% 6/373	1.3% 5/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.27% 1/373	0.54% 2/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cartilage neoplasm	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/373	0.54% 2/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal cancer metastatic	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.27% 1/373	0.00% 0/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.4% 9/373	0.54% 2/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.54% 2/373	1.1% 4/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/373	0.27% 1/371
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyosarcoma	0.27% 1/373	0.00% 0/371
Nervous system disorders Amnesia	0.27% 1/373	0.00% 0/371
Nervous system disorders Autonomic nervous system imbalance	0.00% 0/373	0.27% 1/371
Nervous system disorders Balance disorder	0.00% 0/373	0.27% 1/371
Nervous system disorders Carotid artery stenosis	0.00% 0/373	0.27% 1/371
Nervous system disorders Coma	0.00% 0/373	0.27% 1/371
Nervous system disorders Depressed level of consciousness	0.27% 1/373	0.00% 0/371
Nervous system disorders Dystonia	0.27% 1/373	0.00% 0/371
Nervous system disorders Facial palsy	0.27% 1/373	0.27% 1/371
Nervous system disorders Loss of consciousness	0.27% 1/373	0.54% 2/371
Nervous system disorders Parkinson's disease	0.54% 2/373	0.27% 1/371
Nervous system disorders Parkinsonism	0.54% 2/373	0.54% 2/371
Nervous system disorders Restless legs syndrome	0.27% 1/373	0.00% 0/371
Nervous system disorders Ruptured cerebral aneurysm	0.27% 1/373	0.00% 0/371
Nervous system disorders Sciatica	0.54% 2/373	0.00% 0/371
Nervous system disorders Spinal claudication	0.27% 1/373	0.00% 0/371
Nervous system disorders Stupor	0.00% 0/373	0.27% 1/371
Nervous system disorders Subarachnoid haemorrhage	0.27% 1/373	0.54% 2/371
Nervous system disorders Sudden onset of sleep	0.27% 1/373	0.54% 2/371
Nervous system disorders Syncope	0.00% 0/373	0.27% 1/371
Nervous system disorders Transient ischaemic attack	0.00% 0/373	0.27% 1/371
Nervous system disorders Tremor	0.27% 1/373	0.00% 0/371
Psychiatric disorders Delirium	0.27% 1/373	0.00% 0/371
Psychiatric disorders Depression	0.27% 1/373	0.00% 0/371
Psychiatric disorders Disorientation	0.27% 1/373	0.00% 0/371
Psychiatric disorders Hallucination	0.27% 1/373	0.00% 0/371
Psychiatric disorders Hallucination, visual	0.27% 1/373	0.00% 0/371
Psychiatric disorders Hypersexuality	0.27% 1/373	0.00% 0/371
Psychiatric disorders Mental status changes	0.00% 0/373	0.54% 2/371
Psychiatric disorders Rapid eye movements sleep abnormal	0.27% 1/373	0.27% 1/371
Psychiatric disorders Stress	0.27% 1/373	0.00% 0/371
Renal and urinary disorders Urinary fistula	0.27% 1/373	0.00% 0/371
Renal and urinary disorders Urinary retention	0.54% 2/373	0.00% 0/371
Reproductive system and breast disorders Benign prostatic hyperplasia	0.27% 1/373	0.00% 0/371
Reproductive system and breast disorders Ovarian cyst	0.00% 0/373	0.27% 1/371
Reproductive system and breast disorders Prostatitis	0.27% 1/373	0.00% 0/371
Reproductive system and breast disorders Uterine prolapse	0.27% 1/373	0.00% 0/371
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/373	0.27% 1/371
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/373	0.27% 1/371
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/373	0.27% 1/371
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.54% 2/373	0.81% 3/371
Respiratory, thoracic and mediastinal disorders Pharyngeal hypoaesthesia	0.27% 1/373	0.00% 0/371
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.27% 1/373	0.00% 0/371
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.27% 1/373	0.00% 0/371
Skin and subcutaneous tissue disorders Precancerous skin lesion	0.27% 1/373	0.00% 0/371
Vascular disorders Aortic aneurysm	0.00% 0/373	0.27% 1/371
Vascular disorders Circulatory collapse	0.00% 0/373	0.54% 2/371
Vascular disorders Deep vein thrombosis	0.27% 1/373	0.00% 0/371
Vascular disorders Orthostatic hypotension	0.27% 1/373	0.54% 2/371
Vascular disorders Peripheral ischaemia	0.27% 1/373	0.00% 0/371
Vascular disorders Phlebitis superficial	0.27% 1/373	0.00% 0/371
Vascular disorders Subclavian artery stenosis	0.27% 1/373	0.00% 0/371
Vascular disorders Thrombosis	0.27% 1/373	0.27% 1/371
Vascular disorders Varicose vein	0.00% 0/373	0.27% 1/371

Other adverse events

Other adverse events
Measure	Carbidopa/Levodopa/Entacapone n=373 participants at risk Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.	Carbidopa/Levodopa n=371 participants at risk Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks.
Gastrointestinal disorders Constipation	13.4% 50/373	11.9% 44/371
Gastrointestinal disorders Diarrhoea	17.4% 65/373	7.5% 28/371
Gastrointestinal disorders Dry mouth	5.1% 19/373	3.5% 13/371
Gastrointestinal disorders Dyspepsia	3.8% 14/373	5.4% 20/371
Gastrointestinal disorders Nausea	30.6% 114/373	18.9% 70/371
Gastrointestinal disorders Vomiting	5.9% 22/373	2.4% 9/371
General disorders Fatigue	10.7% 40/373	11.3% 42/371
General disorders Oedema peripheral	7.2% 27/373	9.2% 34/371
Infections and infestations Bronchitis	5.4% 20/373	5.4% 20/371
Infections and infestations Nasopharyngitis	9.1% 34/373	11.6% 43/371
Infections and infestations Upper respiratory tract infection	5.1% 19/373	4.6% 17/371
Infections and infestations Urinary tract infection	5.4% 20/373	6.5% 24/371
Injury, poisoning and procedural complications Fall	7.5% 28/373	9.7% 36/371
Musculoskeletal and connective tissue disorders Arthralgia	10.2% 38/373	11.6% 43/371
Musculoskeletal and connective tissue disorders Back pain	12.6% 47/373	14.3% 53/371
Musculoskeletal and connective tissue disorders Muscle spasms	5.4% 20/373	5.7% 21/371
Musculoskeletal and connective tissue disorders Pain in extremity	9.9% 37/373	8.6% 32/371
Nervous system disorders Dizziness	15.8% 59/373	12.4% 46/371
Nervous system disorders Dyskinesia	5.6% 21/373	2.7% 10/371
Nervous system disorders Headache	9.9% 37/373	7.0% 26/371
Nervous system disorders Somnolence	9.9% 37/373	7.5% 28/371
Nervous system disorders Tremor	2.9% 11/373	7.0% 26/371
Psychiatric disorders Abnormal dreams	6.7% 25/373	4.6% 17/371
Psychiatric disorders Anxiety	9.9% 37/373	7.3% 27/371
Psychiatric disorders Depression	15.3% 57/373	13.7% 51/371
Psychiatric disorders Insomnia	12.6% 47/373	14.3% 53/371
Skin and subcutaneous tissue disorders Rash	3.5% 13/373	5.1% 19/371
Vascular disorders Hypertension	5.1% 19/373	7.3% 27/371
Vascular disorders Orthostatic hypotension	5.1% 19/373	3.0% 11/371

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER