Trial Outcomes & Findings for Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease (NCT NCT01230801)

NCT ID: NCT01230801

Last Updated: 2018-06-11

Results Overview

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2018-06-11

Participant Flow

Participant milestones

Measure	BMN 701 5 mg/kg BMN 701 5 mg/kg IV	BMN 701 10 mg/kg BMN 701 10 mg/kg IV	BMN 701 20 mg/kg BMN 701 20 mg/kg IV
Overall Study STARTED	3	3	16
Overall Study COMPLETED	3	3	15
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease

Baseline characteristics by cohort

Measure	BMN 701 5 mg/kg n=3 Participants BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	22 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	51.7 years STANDARD_DEVIATION 6.81 • n=5 Participants	42.3 years STANDARD_DEVIATION 12.90 • n=7 Participants	50.1 years STANDARD_DEVIATION 5.37 • n=5 Participants	49.3 years STANDARD_DEVIATION 7.00 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	16 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Australia	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment France	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Safety Population

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Outcome measures

Measure	BMN 701 5 mg/kg n=3 Participants BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total Total Results
Number of Participants With Adverse Events	3 Participants	3 Participants	15 Participants	—

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.

Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes

Outcome measures

Measure	BMN 701 5 mg/kg n=3 Participants BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Six Minutes Walk Test Baseline	334 meter Standard Deviation 227.12	360 meter Standard Deviation 51.4	354.5 meter Standard Deviation 156.94	352.5 meter Standard Deviation 151.05
Change From Baseline in Six Minutes Walk Test Change from Baseline - Week 6	-2.5 meter Standard Deviation 23.33	-30.3 meter Standard Deviation 56.50	19.8 meter Standard Deviation 35.11	10.5 meter Standard Deviation 40.08
Change From Baseline in Six Minutes Walk Test Change from Baseline - Week 12	31.2 meter Standard Deviation 78.81	-13.7 meter Standard Deviation 8.04	11.1 meter Standard Deviation 42.67	10.4 meter Standard Deviation 45.32
Change From Baseline in Six Minutes Walk Test Change from Baseline - Week 18	43.3 meter Standard Deviation 89.44	-79.0 meter Standard Deviation 104.61	16.4 meter Standard Deviation 55.09	6.6 meter Standard Deviation 73.43
Change From Baseline in Six Minutes Walk Test Change from Baseline - Week 24	36.0 meter Standard Deviation 76.02	-42.7 meter Standard Deviation 12.57	22.3 meter Standard Deviation 54.23	15.3 meter Standard Deviation 56.97

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 week

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.

Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Outcome measures

Measure	BMN 701 5 mg/kg n=3 Participants BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Percent Predicted Upright Forced Vital Capacity Baseline	69.3 percentage of Predicted Upright FVC Standard Deviation 19.73	67.3 percentage of Predicted Upright FVC Standard Deviation 26.58	58.1 percentage of Predicted Upright FVC Standard Deviation 18.42	60.9 percentage of Predicted Upright FVC Standard Deviation 19.21
Change From Baseline in Percent Predicted Upright Forced Vital Capacity Change from Baseline - Week 6	4.0 percentage of Predicted Upright FVC Standard Deviation 4.24	-2.0 percentage of Predicted Upright FVC Standard Deviation 2.65	0.4 percentage of Predicted Upright FVC Standard Deviation 3.3	0.4 percentage of Predicted Upright FVC Standard Deviation 3.46
Change From Baseline in Percent Predicted Upright Forced Vital Capacity Change from Baseline - Week 12	-2.6 percentage of Predicted Upright FVC Standard Deviation 9.5	-3.7 percentage of Predicted Upright FVC Standard Deviation 2.89	1.6 percentage of Predicted Upright FVC Standard Deviation 4.35	0.3 percentage of Predicted Upright FVC Standard Deviation 5.25
Change From Baseline in Percent Predicted Upright Forced Vital Capacity Change from Baseline - Week 18	1.5 percentage of Predicted Upright FVC Standard Deviation 4.09	0.3 percentage of Predicted Upright FVC Standard Deviation 3.06	1.2 percentage of Predicted Upright FVC Standard Deviation 4.49	1.1 percentage of Predicted Upright FVC Standard Deviation 4.1
Change From Baseline in Percent Predicted Upright Forced Vital Capacity Change from Baseline - Week 24	1.0 percentage of Predicted Upright FVC Standard Deviation 2.65	-1.7 percentage of Predicted Upright FVC Standard Deviation 3.06	1.2 percentage of Predicted Upright FVC Standard Deviation 3.89	0.8 percentage of Predicted Upright FVC Standard Deviation 3.65

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 weeks

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.

Change from Baseline in Percent Predicted Supine Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Outcome measures

Measure	BMN 701 5 mg/kg n=3 Participants BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Percent Predicted Supine Forced Vital Capacity Baseline	36.7 percentage of Predicted Supine FVC Standard Deviation 17.95	47.7 percentage of Predicted Supine FVC Standard Deviation 32.58	46.3 percentage of Predicted Supine FVC Standard Deviation 21.93	45 percentage of Predicted Supine FVC Standard Deviation 22.1
Change From Baseline in Percent Predicted Supine Forced Vital Capacity Change from Baseline - Week 6	2.1 percentage of Predicted Supine FVC Standard Deviation 1.2	-1.3 percentage of Predicted Supine FVC Standard Deviation 4.04	-0.8 percentage of Predicted Supine FVC Standard Deviation 4.86	-0.6 percentage of Predicted Supine FVC Standard Deviation 4.44
Change From Baseline in Percent Predicted Supine Forced Vital Capacity Change from Baseline - Week 24	2.0 percentage of Predicted Supine FVC Standard Deviation 3.0	-3.3 percentage of Predicted Supine FVC Standard Deviation 5.51	1.1 percentage of Predicted Supine FVC Standard Deviation 4.42	0.5 percentage of Predicted Supine FVC Standard Deviation 4.53
Change From Baseline in Percent Predicted Supine Forced Vital Capacity Change from Baseline - Week 12	0.3 percentage of Predicted Supine FVC Standard Deviation 4.22	-4.7 percentage of Predicted Supine FVC Standard Deviation 2.89	3.3 percentage of Predicted Supine FVC Standard Deviation 3.87	1.5 percentage of Predicted Supine FVC Standard Deviation 4.7
Change From Baseline in Percent Predicted Supine Forced Vital Capacity Change from Baseline - Week 18	1.3 percentage of Predicted Supine FVC Standard Deviation 1.53	-1.3 percentage of Predicted Supine FVC Standard Deviation 6.66	2.3 percentage of Predicted Supine FVC Standard Deviation 3.14	1.5 percentage of Predicted Supine FVC Standard Deviation 3.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 weeks

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.

Change from Baseline in Percent Predicted Upright Maximum Expiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Outcome measures

Measure	BMN 701 5 mg/kg BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure Change from Baseline - Week 18	—	1.2 percentage of Predicted MEP Standard Deviation 2.06	6.9 percentage of Predicted MEP Standard Deviation 7.21	6.0 percentage of Predicted MEP Standard Deviation 6.94
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure Baseline	—	31.1 percentage of Predicted MEP Standard Deviation 6.64	36.3 percentage of Predicted MEP Standard Deviation 15.46	35.5 percentage of Predicted MEP Standard Deviation 14.42
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure Change from Baseline - Week 6	—	6.8 percentage of Predicted MEP Standard Deviation 4.06	3.2 percentage of Predicted MEP Standard Deviation 5.38	3.8 percentage of Predicted MEP Standard Deviation 5.27
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure Change from Baseline - Week 12	—	1.4 percentage of Predicted MEP Standard Deviation 4.53	2.2 percentage of Predicted MEP Standard Deviation 8.68	2.0 percentage of Predicted MEP Standard Deviation 8.07
Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure Change from Baseline - Week 24	—	2.5 percentage of Predicted MEP Standard Deviation 10.4	5.2 percentage of Predicted MEP Standard Deviation 8.25	4.8 percentage of Predicted MEP Standard Deviation 8.36

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 weeks

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.

Change from Baseline in Percent Predicted Upright Maximum Inspiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Outcome measures

Measure	BMN 701 5 mg/kg BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure Change from baseline at week 12	—	3.4 percentage of Predicted MIP Standard Deviation 6.74	11.4 percentage of Predicted MIP Standard Deviation 10.92	10.1 percentage of Predicted MIP Standard Deviation 10.65
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure Change from baseline at week 18	—	2.9 percentage of Predicted MIP Standard Deviation 11.77	14.5 percentage of Predicted MIP Standard Deviation 14.48	12.6 percentage of Predicted MIP Standard Deviation 14.45
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure Change from baseline at week 24	—	0.7 percentage of Predicted MIP Standard Deviation 6.69	11.1 percentage of Predicted MIP Standard Deviation 8.31	9.5 percentage of Predicted MIP Standard Deviation 8.81
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure Baseline	—	39.5 percentage of Predicted MIP Standard Deviation 21.87	40.5 percentage of Predicted MIP Standard Deviation 25.01	40.3 percentage of Predicted MIP Standard Deviation 23.97
Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure Change from baseline at week 6	—	1.7 percentage of Predicted MIP Standard Deviation 1.46	5.3 percentage of Predicted MIP Standard Deviation 9.8	4.7 percentage of Predicted MIP Standard Deviation 9.06

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 24 weeks

Population: ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg.

Change from Baseline in Upright Maximum Ventilatory Volume. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Outcome measures

Measure	BMN 701 5 mg/kg BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 Participants BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 Participants BMN 701 20 mg/kg IV	Total n=22 Participants Total Results
Change From Baseline in Upright Maximum Ventilatory Volume Baseline	—	76 L/min Standard Deviation 41.04	67.6 L/min Standard Deviation 25.9	68.9 L/min Standard Deviation 27.5
Change From Baseline in Upright Maximum Ventilatory Volume Change from Baseline - Week 6	—	-1.0 L/min Standard Deviation 0.35	1.5 L/min Standard Deviation 11.1	1.1 L/min Standard Deviation 10.18
Change From Baseline in Upright Maximum Ventilatory Volume Change from Baseline - Week 12	—	-1.1 L/min Standard Deviation 2.73	3.8 L/min Standard Deviation 11.64	3.0 L/min Standard Deviation 10.82
Change From Baseline in Upright Maximum Ventilatory Volume Change from Baseline - Week 18	—	-3.9 L/min Standard Deviation 2.86	4.7 L/min Standard Deviation 10.89	3.3 L/min Standard Deviation 10.46
Change From Baseline in Upright Maximum Ventilatory Volume Change from Baseline - Week 24	—	-0.7 L/min Standard Deviation 9.1	2.3 L/min Standard Deviation 10.71	1.8 L/min Standard Deviation 10.28

Adverse Events

BMN 701 5 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

BMN 701 10 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

BMN 701 20 mg/kg

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Total

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	BMN 701 5 mg/kg n=3 participants at risk BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 participants at risk BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 participants at risk BMN 701 20 mg/kg IV	Total n=22 participants at risk Total Results
Immune system disorders Hypersensitivity	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Aggression	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Hypertensive crisis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)

Other adverse events

Measure	BMN 701 5 mg/kg n=3 participants at risk BMN 701 5 mg/kg IV	BMN 701 10 mg/kg n=3 participants at risk BMN 701 10 mg/kg IV	BMN 701 20 mg/kg n=16 participants at risk BMN 701 20 mg/kg IV	Total n=22 participants at risk Total Results
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Laceration	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Procedural pain	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Investigations Body temperature increased	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Investigations Blood glucose decreased	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	100.0% 3/3 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.8% 7/22 • Number of events 11 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Cardiac disorders Bradycardia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Cardiac disorders Bundle branch block right	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Cardiac disorders Palpitations	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Cardiac disorders Sinus tachycardia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Cardiac disorders Tachycardia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	25.0% 4/16 • Number of events 16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	22.7% 5/22 • Number of events 18 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Eye disorders Diplopia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Eye disorders Vision blurred	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Abdominal tenderness	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Constipation	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	25.0% 4/16 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	22.7% 5/22 • Number of events 6 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Dry mouth	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Dysphagia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Epigastric discomfort	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Gastritis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Nausea	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	50.0% 8/16 • Number of events 15 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	36.4% 8/22 • Number of events 15 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Retching	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Tongue discolouration	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.2% 5/16 • Number of events 9 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.8% 7/22 • Number of events 11 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Application site erythema	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Asthenia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Chest discomfort	33.3% 1/3 • Number of events 6 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.2% 5/16 • Number of events 6 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.8% 7/22 • Number of events 14 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Chills	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Fatigue	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Feeling cold	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Feeling hot	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Infusion site discomfort	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Local swelling	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Malaise	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Non-cardiac chest pain	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Oedema peripheral	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Pain	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Pyrexia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Tenderness	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Thirst	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Vaccination site inflammation	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
General disorders Vessel puncture site bruise	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Candida infection	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Laryngitis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Localised infection	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Nasopharyngitis	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Sinusitis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Tooth abscess	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Infections and infestations Urinary tract infection	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Animal bite	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Injury, poisoning and procedural complications Contusion	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	22.7% 5/22 • Number of events 6 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Investigations Cardiac murmur	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Investigations Complement factor decreased	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Investigations Respiratory rate increased	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Hyperphagia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	87.5% 14/16 • Number of events 41 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	63.6% 14/22 • Number of events 41 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Back pain	66.7% 2/3 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 7 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Neck pain	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Disturbance in attention	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Dizziness	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	37.5% 6/16 • Number of events 9 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.8% 7/22 • Number of events 10 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Headache	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	66.7% 2/3 • Number of events 8 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	37.5% 6/16 • Number of events 27 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	40.9% 9/22 • Number of events 37 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Hypoaesthesia	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Lethargy	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Paraesthesia	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Nervous system disorders Tremor	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Anxiety	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Confusional state	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Depression	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Depressive symptom	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Psychiatric disorders Nervousness	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Renal and urinary disorders Haematuria	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	31.2% 5/16 • Number of events 10 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	27.3% 6/22 • Number of events 12 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Hypopnoea	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Eczema	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	25.0% 4/16 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.2% 4/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 4 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 13 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 14 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Flushing	33.3% 1/3 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 6 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Haematoma	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Hot flush	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Hypertension	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	18.8% 3/16 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	13.6% 3/22 • Number of events 5 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Hypotension	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Pallor	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	12.5% 2/16 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	9.1% 2/22 • Number of events 2 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Poor venous access	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	33.3% 1/3 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/16 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Systolic hypertension	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)
Vascular disorders Venous thrombosis	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	0.00% 0/3 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	6.2% 1/16 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)	4.5% 1/22 • Number of events 1 • 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up)

Additional Information

Manager, Clinical Operations

BioMarin Pharmaceutical Inc.

Phone: 415-455-7448

Email: Slava.Titov@bmrn.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60