Long-term Safety Study of Open-label Pramipexole Extended... | NCT00601523

ID	Type	Description	Link
2007-004234-16	EudraCT Number	EudraCT

Status Module

Label	Type	Description	Intervention Names
Pramipexole	Active Comparator	Patient to receive Pramipexole ER 0.375-4.5 mg tabl form daily	Drug: Pramipexole
Placebo	Placebo Comparator	Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events	The aim of this study was to obtain long-term safety and tolerability data on pramipexole ER, in patients who have previously completed a pramipexole double blind study in early PD (248.524 (NCT00479401) or 248.636 (NCT00558025)). Therefore these items were considered as a safety evaluation	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

Secondary Outcomes

Measure	Description	Time Frame
Unified Parkinson's Disease Rating Scale (UPDRS) II+III Total Score: Change From Baseline	UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms	Open Label (OL) baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Completion of the double-blind trial 248.524 or 248.636
Male or female patient with early idiopathic Parkinson´s disease (PD), and with a Modified Hoehn and Yahr stage of I to III.
Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislation).

Exclusion criteria:

Patients prematurely withdrawn from the double-blind trials 248.524 or 248.636.
Atypical parkinsonian syndromes due to drugs,metabolic disorders, encephalitis or degenerative diseases.
Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study.4.History of psychosis, except history of drug induced hallucinations.

5. Clinically significant electrocardiogram (ECG) abnormalities at baseline. 6.Clinically significant hypotension 7.Malignant melanoma or history of previously treated malignant melanoma. 8.Any other clinically significant disease, that could put the patient at risk or could prevent compliance or completion of the study. 9. Pregnancy or breast-feeding.

10. Sexually active female of childbearing potential not using a medically approved method of birth control for at least one month prior to the baseline and throughout the study.11 Serum levels of aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 upper limit of normal (ULN) at baseline 12. Patients with a creatinine clearance < 50 mL/min (estimated by the Cockcroft and Gault formula). 13. Motor complications under levodopa therapy (e.g. on-off phenomena, dyskinesia) at baseline.

14. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit. 15.Any of the following drugs within 4 weeks prior to baseline: methylphenidate, cinnarizine, amphetamines. 16. Flunarizine within 3 months prior to baseline.

17. Known hypersensitivity to pramipexole or its excipients. 18. Drug abuse (including alcohol), according to investigator´s judgement, within 2 years prior to baseline.

19. Participation in investigational drug studies other than trials 248.524 and 248.636 or use of other investigational drug within one month or five times the half-life of the investigational drug prior to baseline.

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
248.633.01004 Boehringer Ingelheim Investigational Site		Sun City	Arizona		United States
248.633.01018 Boehringer Ingelheim Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Patients From 248.524	Pramipexole ER 0.375-4.5 mg. Stratified cohort of patients who had previously completed 248.524 (NCT00479401) and previously received Pramipexole Extended Release (PPX ER), Pramipexole Immediate Release (PPX IR), or Placebo.
FG001	Patients From 248.636

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Unified Parkinson's Disease Rating Scale (UPDRS) II+III Total Score: Change From Baseline

UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

Patients from Full Analysis Set (FAS included all patients who received at least one dose of study medication and had at least one post-baseline efficacy assessment) and who had values for UPDRS II+III at week 80 (patients from 248.524) or at week 72 (patients from 248.636)

Posted

Mean

Standard Deviation

Units of scale

Open Label (OL) baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000290 OG001113

Title

Denominators

Categories

Title	Measurements
	OG0002.2± 9.5 OG0011.5± 7.7

Secondary

Number of Patients With UPDRS II+III Response From OL Baseline at Week 80 (Patients From 248.524) or Week 72 (Patients From 248.636)

A response means an improvement of >=20% from OL baseline. UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

Posted

Number

Patients

OL Baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants

Secondary

UPDRS I Total Score: Change From OL Baseline

UPDRS I ranging from 0 (normal) to 16 (severe), measures Mentation, Behavior and Mood

Patients from FAS and who had values for UPDRS I at week 80 (patients from 248.524) or at week 72 (patients from 248.636)

Posted

Mean

Standard Deviation

Units of scale

OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

UPDRS II Total Score: Change From OL Baseline

UPDRS II ranging from 0 (normal) to 52 (severe), measures activity of daily living.

Patients from FAS and who had values for UPDRS II at week 80 (patients from 248.524) or at week 72 (patients from 248.636)

Posted

Mean

Standard Deviation

Units of scale

OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

UPDRS III Total Score: Change From OL Baseline

UPDRS III ranging from 0 (normal) to 108 (severe) measures motor symptoms

Patients from FAS and who had values for UPDRS III at week 80 (patients from 248.524) or at week 72 (patients from 248.636)

Posted

Mean

Standard Deviation

Units of scale

OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Response in Clinical Global Impression of Improvement (CGI-I)

Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning very much worse. For patients previously treated with Placebo, all patients with at least "much improved" were considered as responders. For patients previously treated with Pramipexole ER or Immediate Release (IR), all patients with no change to very much improved were considered as responders

Patients from FAS and who had values for for CGI-I at week 32 (patients from 248.524) or at week 24 (patients from 248.636)

Posted

Number

Patients

OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Response in Patient Global Impression of Improvement (PGI-I)

Patient rated evaluation of the PD symptoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning very much worse. For patients previously treated with Placebo, all patients with at least "much better" were considered as responders. For patients previously treated with pramipexole (PPX) ER or IR, all patients with no change to very much better were considered as responders

Patients from FAS and who had values for for PGI-I at week 32 (patients from 248.524) or at week 24 (patients from 248.636)

Posted

Number

Patients

OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Parkinson Fatigue Scale (PFS-16) : Change From OL Baseline

PFS-16 ranging from 16 (better perceived health status) to 80 (severe symptoms of the disease) measuring aspects of fatigue that are relevant to patients with PD.

Patients from FAS and who had values for PFS-16 at week 80 (patients from 248.524) or at week 72 (patients from 248.636)

Posted

Mean

Standard Deviation

Units of scale

OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Number of Patients Introducing L-Dopa Medication in OL Trial

Number of patients requiring Levodopa supplementation during the study

Patients from FAS

Posted

Number

Patients

80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

L-Dopa Dose: Change From OL Baseline

Change from open-label baseline in Levodopa dose

Patients from FAS and with L-Dopa at OL baseline and at week 80 (patients from 248.524) or week 72 (patients from 248.636)

Posted

Number

Patients

OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Pramipexole Doses Respectively After 80 Weeks Compared to Pramipexole Doses at Week 8 for Previously 248.524 Patients and After 72 Weeks Compared to Pramipexole Doses at Week 0 for Previously 248.636 Patients

Change from open-label baseline in Levodopa dose over the final 72 weeks of open-label assessment

Patients from Treated Set (defined as all patients who were dispensed study drug and were documented to have at least one dose of investigational treatment) and treated until week 80 (patients from 248.524) or week 72 (patients from 248.636)

Posted

Number

Patients

Week 8 and week 80 (patients from 248.524) or week 0 and week 72 (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Primary

Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events

The aim of this study was to obtain long-term safety and tolerability data on pramipexole ER, in patients who have previously completed a pramipexole double blind study in early PD (248.524 (NCT00479401) or 248.636 (NCT00558025)). Therefore these items were considered as a safety evaluation

Patients from Treated Set (defined as all patients who were dispensed study drug and were documented to have at least one dose of investigational treatment)

Posted

Number

Percentage of participants

80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Patient Preference Regarding Treatment Dosing

Patients were surveyed on their preference for Once Daily dosing versus Three Times Daily dosing

Patients from Full Analysis Set (FAS included all patients who received at least one dose of study medication and had at least one post-baseline efficacy assessment)

Posted

Number

participants

80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Secondary

Patient Rating of Convenience of Treatment Dosing

Patients were surveyed on the convenience of Once Daily dosing versus Three Times Daily dosing

Patients from Full Analysis Set (FAS included all patients who received at least one dose of study medication and had at least one post-baseline efficacy assessment)

Posted

Number

participants

80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

ID	Title	Description
OG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
OG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0011 affected143 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0010 affected143 at risk
Angina pectoris	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Bradycardia	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Cardiac tamponade	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Coronary artery disease	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0010 affected143 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Left ventricular failure	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Myocardial infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected368 at risk EG0011 affected143 at risk
Myocardial rupture	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Enteritis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Drowning	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Malaise	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Hepatitis	Hepatobiliary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Borrelia infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Bronchitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Endocarditis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Herpes zoster	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Pneumonia	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0011 affected143 at risk
Prostatic abscess	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Respiratory tract infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Septic shock	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0003 affected368 at risk EG0015 affected143 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0013 affected143 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0010 affected143 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0011 affected143 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Arthroscopy	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0012 affected143 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Aphasia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Cervical root pain	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Epilepsy	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
On and off phenomenon	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Parkinson's disease	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0012 affected143 at risk
Sciatica	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Confusional state	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Hallucination	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0011 affected143 at risk
Psychotic disorder	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected368 at risk EG0010 affected143 at risk
Sleep attacks	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Hydroureter	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0011 affected143 at risk
Cystocele	Reproductive system and breast disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected368 at risk EG0011 affected143 at risk
Varicose vein	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected368 at risk EG0010 affected143 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG00025 affected368 at risk EG0017 affected143 at risk
Constipation	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG00015 affected368 at risk EG0019 affected143 at risk
Nausea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG00037 affected368 at risk EG00110 affected143 at risk
Oedema peripheral	General disorders	MedDRA (13.0)	Systematic Assessment	EG00045 affected368 at risk EG00115 affected143 at risk
Nasopharyngitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG00029 affected368 at risk EG0018 affected143 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG00020 affected368 at risk EG0011 affected143 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG00040 affected368 at risk EG00113 affected143 at risk
Dizziness	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG00032 affected368 at risk EG0013 affected143 at risk
Parkinson's disease	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0007 affected368 at risk EG00110 affected143 at risk
Somnolence	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG00067 affected368 at risk EG00110 affected143 at risk
Hallucination	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0008 affected368 at risk EG0018 affected143 at risk
Insomnia	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG00019 affected368 at risk EG0016 affected143 at risk

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases

ID	Term
D052160	Benzothiazoles
D013844	Thiazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)
BG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Patients From 248.524	Patients who had previously completed 248.524 (NCT00479401)			53	368	214	368
EG001	Patients From 248.636	Patients who had previously completed 248.636 (NCT00558025)			21	143	62	143