Trial Outcomes & Findings for Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease (NCT NCT02006121)

NCT ID: NCT02006121

Last Updated: 2019-07-08

Results Overview

The least squares mean reduction (improvement) in OFF time as reported by the patient using the Hauser Parkinson's disease home diary. Patients categorised their motor symptoms into OFF, ON with dyskinesia, ON without troublesome dyskinesia or sleeping using half hour blocks over 24 hours. Daily OFF time was computed from the average of valid motor diaries from the two days preceding each visit. Correct diary completion was evaluated during screening and observed by the investigator to ensure patients could categorise their motor symptoms correctly. A diary was considered valid if no more than 4 half-hour periods were either absent or duplicated. There were no invalid diaries at Baseline or Week 12.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 107 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2019-07-08

Participant Flow

Blinded treatment was administered over 12 weeks after which patients could choose to enrol in a 12-month open-label phase. Early switching to the open-label phase was permitted for lack of efficacy in the double-blind phase.

Participant milestones

Measure	Apomorphine Hydrochloride Apo-go® Apomorphine hydrochloride 5 mg/ml solution in 10 mL pre-filled syringes for continuous infusion during the waking day using a Cane CRONO APO-Go® infusion pump. Hourly flow rate adjusted in increments of 0.5-1.0 mg/hour/day during titration to reach the patient's individualized required dose in a range of 3-8 mg/hour for 14-18 hours per day. Concomitant medications were reduced/discontinued in the following order: dopamine agonists, MAO-B inhibitors, COMT inhibitors, levodopa dose then frequency.	Placebo Blinded Placebo: saline infusion; Open Label, placebo switched to apomorphine infusion. Blinded phase: Sodium chloride 9 mg/ml continuous infusion during the waking day using a Cane CRONO APO-Go® infusion pump. Hourly flow rate adjusted in increments of 0.5-1.0 mg/hour/day during titration to reach the patient's individualized required dose in a range of 3-8 mg/hour for 14-18 hours per day. Concomitant medications were reduced/discontinued in the following order: dopamine agonists, MAO-B inhibitors, COMT inhibitors, levodopa dose then frequency. Open Label phase: as per apomorphine arm
Double Blind Phase STARTED	54	53
Double Blind Phase COMPLETED	42	29
Double Blind Phase NOT COMPLETED	12	24
Open Label Phase STARTED	84	0
Open Label Phase COMPLETED	59	0
Open Label Phase NOT COMPLETED	25	0

Reasons for withdrawal

Measure	Apomorphine Hydrochloride Apo-go® Apomorphine hydrochloride 5 mg/ml solution in 10 mL pre-filled syringes for continuous infusion during the waking day using a Cane CRONO APO-Go® infusion pump. Hourly flow rate adjusted in increments of 0.5-1.0 mg/hour/day during titration to reach the patient's individualized required dose in a range of 3-8 mg/hour for 14-18 hours per day. Concomitant medications were reduced/discontinued in the following order: dopamine agonists, MAO-B inhibitors, COMT inhibitors, levodopa dose then frequency.	Placebo Blinded Placebo: saline infusion; Open Label, placebo switched to apomorphine infusion. Blinded phase: Sodium chloride 9 mg/ml continuous infusion during the waking day using a Cane CRONO APO-Go® infusion pump. Hourly flow rate adjusted in increments of 0.5-1.0 mg/hour/day during titration to reach the patient's individualized required dose in a range of 3-8 mg/hour for 14-18 hours per day. Concomitant medications were reduced/discontinued in the following order: dopamine agonists, MAO-B inhibitors, COMT inhibitors, levodopa dose then frequency. Open Label phase: as per apomorphine arm
Double Blind Phase Adverse Event	6	0
Double Blind Phase Lack of Efficacy	1	16
Double Blind Phase Withdrawal by Subject	3	4
Double Blind Phase Non-compliance with study drug	1	3
Double Blind Phase Minimum infusion rate poorly tolerated	1	0
Double Blind Phase Inconvenience of infusion system	0	1
Open Label Phase Adverse Event	15	0
Open Label Phase Lack of Efficacy	2	0
Open Label Phase Protocol Violation	2	0
Open Label Phase Withdrawal by Subject	3	0
Open Label Phase Non-compliance with study drug	3	0

Baseline Characteristics

Clinical Trial of Apomorphine Subcutaneous Infusion in Patients With Advanced Parkinson's Disease

Baseline characteristics by cohort

Measure	Apomorphine Hydrochloride n=53 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=52 Participants Placebo: saline infusion Sodium chloride 9 mg/ml	Total n=105 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Age, Continuous	63.58 years STANDARD_DEVIATION 9.32 • n=5 Participants	63.00 years STANDARD_DEVIATION 8.32 • n=7 Participants	63.29 years STANDARD_DEVIATION 8.80 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	32 Participants n=7 Participants	66 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: All randomised patients excluding those who had major protocol deviations who received at least one dose of trial medication during the course of the trial and for whom any post-baseline efficacy assessment is available.

The least squares mean reduction (improvement) in OFF time as reported by the patient using the Hauser Parkinson's disease home diary. Patients categorised their motor symptoms into OFF, ON with dyskinesia, ON without troublesome dyskinesia or sleeping using half hour blocks over 24 hours. Daily OFF time was computed from the average of valid motor diaries from the two days preceding each visit. Correct diary completion was evaluated during screening and observed by the investigator to ensure patients could categorise their motor symptoms correctly. A diary was considered valid if no more than 4 half-hour periods were either absent or duplicated. There were no invalid diaries at Baseline or Week 12.

Outcome measures

Measure	Apomorphine Hydrochloride n=53 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=52 Participants Placebo: saline infusion Sodium chloride 9 mg/ml
Mean Change in Daily OFF Time From Baseline (Start of Blinded Treatment) to the End of Double-blind Phase (Visit 10) Based on Patient Diaries Using MMRM mITT Population	-2.61 Hours Interval -3.43 to -1.8	-0.75 Hours Interval -1.66 to 0.16

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All randomised patients excluding those who had major protocol deviations who received at least one dose of trial medication during the course of the trial and for whom any post-baseline efficacy assessment is available.

The least squares mean change in "ON time without troublesome dyskinesia" as reported by the patient using the Hauser Parkinson's disease home diary. Each half hour of the day categorised as OFF, ON with dyskinesia, ON without troublesome dyskinesia or asleep. "ON time without troublesome dyskinesia" measures good ON time for a Parkinson's disease patient.

Outcome measures

Measure	Apomorphine Hydrochloride n=53 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=52 Participants Placebo: saline infusion Sodium chloride 9 mg/ml
Mean Change in Daily Time Spent "ON Without Troublesome Dyskinesia" From Baseline to the End of the Double-blind Phase (Visit 10), Based on Patient Diaries Using MMRM mITT Population	2.90 Hours Interval 2.07 to 3.73	0.85 Hours Interval -0.09 to 1.78

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All randomised patients excluding those who had major protocol deviations who received at least one dose of trial medication during the course of the trial and for whom any post-baseline efficacy assessment is available and who completed the PGIC questionnaire

PGIC is a self-administered questionnaire measuring personal general state of health on a 7-point rating scale. The 7 ordinal categories from which patients must choose are 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse. Results are presented as the % of patients who reported at least minimal improvement in general health status at week 12 compared to Baseline. A Wilcoxon range sum test was performed to test for treatment differences from baseline to end of 12 weeks' treatment period.

Outcome measures

Measure	Apomorphine Hydrochloride n=43 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=34 Participants Placebo: saline infusion Sodium chloride 9 mg/ml
Patient Global Impression of Change (PGIC), Using the mITT Population	79.1 % of participants	23.5 % of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients who received at least one dose of randomized study medication and had at least one post-baseline observation for the primary endpoint

The least squares mean change in oral levodopa dose from Baseline to Visit 10 (week 12) was calculated excluding 3 centres who declined to participate in collecting the necessary details of PRN use of levodopa.

Outcome measures

Measure	Apomorphine Hydrochloride n=41 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=32 Participants Placebo: saline infusion Sodium chloride 9 mg/ml
Mean Change in Oral Levodopa Dose From Baseline to Visit 10 Using MMRM for the mITT Population	-242.09 mg Interval -346.58 to -137.61	-76.46 mg Interval -185.17 to 32.25

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All randomized patients treated at least once with study medication and who had at least one post-baseline observation for the primary endpoint

Levodopa equivalent dose is an indication of the burden of medication taken to control symptoms of Parkinson's disease with all medications other than levodopa itself being converted to a calculated levodopa dose using the methodology published by Tomlinson et al, 2010. The computation of LED excludes the study drug.

Outcome measures

Measure	Apomorphine Hydrochloride n=49 Participants Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=48 Participants Placebo: saline infusion Sodium chloride 9 mg/ml
Mean Change in Levodopa Equivalent Dose From Baseline to Visit 10 (Week 12) Using MMRM in the mITT Population	-502.02 mg Interval -626.45 to -377.6	-150.87 mg Interval -280.14 to -21.59

Adverse Events

Apomorphine Hydrochloride

Serious events: 23 serious events

Other events: 94 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Apomorphine Hydrochloride n=98 participants at risk Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=53 participants at risk Placebo: saline infusion Sodium chloride 9 mg/ml
Psychiatric disorders Confusional state	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Depression	0.00% 0/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Blood and lymphatic system disorders Lymphopenia	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Cardiac disorders Myocardial infarction	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Colitis	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Infusion site cellulitis	2.0% 2/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Investigations Eosinophil count decreased	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Investigations Haematocrit decreased	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Blood and lymphatic system disorders Blood disorder	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Investigations Haemoglobin decreased	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Investigations Red blood cell count decreased	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Vascular disorders Hypotension	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Constipation	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Diarrhoea	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Umbilical hernia	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Chest pain	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Infusion site extravasation	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Cardiac disorders Angina pectoris	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Hepatobiliary disorders Cholelithiasis	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Injury, poisoning and procedural complications Fall	2.0% 2/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Injury, poisoning and procedural complications Forearm fracture	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Injury, poisoning and procedural complications Lower limb fracture	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Injury, poisoning and procedural complications Radius fracture	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Musculoskeletal and connective tissue disorders Pathological fracture	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Lower respiratory tract infection	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Pneumonia	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Urosepsis	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Neuroleptic malignant syndrome	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Parkinson's disease	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Carotid artery stenosis	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders On Off phenomenon	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Radicular syndrome	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Delirium	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Product Issues Device difficult to use	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Paranoia	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Renal and urinary disorders Urinary retention	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Surgical and medical procedures Deep brain stimulation	1.0% 1/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.

Other adverse events

Measure	Apomorphine Hydrochloride n=98 participants at risk Apo-go® Apomorphine hydrochloride 5 mg/ml solution for infusion in pre-filled syringe	Placebo n=53 participants at risk Placebo: saline infusion Sodium chloride 9 mg/ml
General disorders Infusion site nodule	46.9% 46/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Infusion site erythema	15.3% 15/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Infusion site haematoma	8.2% 8/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	9.4% 5/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Fatigue	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Oedema peripheral	7.1% 7/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
General disorders Infusion site pruritus	5.1% 5/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Somnolence	19.4% 19/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Headache	10.2% 10/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Dyskinesia	14.3% 14/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Nervous system disorders Dizziness	11.2% 11/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Nausea	20.4% 20/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	9.4% 5/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Vomiting	8.2% 8/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Gastrointestinal disorders Dyspepsia	5.1% 5/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Insomnia	13.3% 13/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Hallucination, visual	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	3.8% 2/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Sleep disorder	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Psychiatric disorders Hallucination	5.1% 5/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Nasopharyngitis	7.1% 7/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	5.7% 3/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Infections and infestations Urinary tract infection	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Musculoskeletal and connective tissue disorders Back pain	7.1% 7/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Vascular disorders Orthostatic hypotension	6.1% 6/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	1.9% 1/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Blood and lymphatic system disorders Eosinophilia	5.1% 5/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.
Investigations Electrocardiogram QT prolonged	5.1% 5/98 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.	0.00% 0/53 • Adverse Events were collected during the double-blind and open label phases of the study. 98 patients were exposed to at least one dose of apomorphine with a cumulative person time of 4081 weeks of exposure. The range of exposure to apomorphine was 37-464 days (mean 397 days). In addition, 53 patients (44 of whom went onto apomorphine in the open label phase) were exposed to placebo treatment in the double blind phase with a maximum 12 weeks of exposure.

Additional Information

Medical Director

Britannia Pharmaceuticals

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Email: reception@britannia-pharm.com

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