Trial Outcomes & Findings for Efficacy and Safety of SPARC0921 in Subjects With Spasticity (NCT NCT01457352)

Last Updated: 2019-06-18

Results Overview

Percentage of subjects who had treatment failure Clinical Global Impression of Change of ≥ 5 and at least one movement with ≥ 1 unit increase in modified Ashworth score from baseline. The modified Ashworth scale is a 6-point scale as follows: Minimum score of 0 (better outcome) = no increase in tone Maximum score of 4 (worst outcome) = affected part(s) rigid inflexion or extension. The clinician (other than the one performing the Modified Ashworth Scale assessment) rated his/her overall (global) impression of change in spasticity using the 7-point scale shown below: Minimum score of 1 (better outcome) = very much improved Maximum score of 7 (very much worse) = very much worse

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

392 participants

Primary outcome timeframe

Week 22

Results posted on

2019-06-18

Participant Flow

The study was conducted in part 1, 2, and 3: Part 1: 392 subjects Part 2: 376 subjects (SPARC0921), one death occurred in Part 2 of the study. Part 3: 296 subjects (SPARC0921 or Placebo0921) Efficacy results are presented for Part 3 and safety results are presented for Part 2 and Part 3 of the study as per the objectives of the study.

Participant milestones

Participant milestones
Measure	SPARC0921 once, twice, thrice, or four times daily for one week	Placebo Placebo formulation
Period 1 STARTED	392	0
Period 1 COMPLETED	376	0
Period 1 NOT COMPLETED	16	0
Period 2 STARTED	376	0
Period 2 COMPLETED	296	0
Period 2 NOT COMPLETED	80	0
Period 3 STARTED	147	149
Period 3 Randomization	147	149
Period 3 COMPLETED	146	144
Period 3 NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	SPARC0921 once, twice, thrice, or four times daily for one week	Placebo Placebo formulation
Period 1 Adverse Event	2	0
Period 1 Withdrawal by Subject	2	0
Period 1 Physician Decision	2	0
Period 1 MS related disease progression	1	0
Period 1 Withdrawn	1	0
Period 1 withdrew per sponsor	1	0
Period 1 Protocol Violation	4	0
Period 1 Did not meet eligibility criteria	3	0
Period 2 Withdrawal by Subject	23	0
Period 2 Adverse Event	22	0
Period 2 no analysis	10	0
Period 2 Lack of Efficacy	8	0
Period 2 Protocol Violation	4	0
Period 2 Sponsor's withdrawal	7	0
Period 2 Lost to Follow-up	1	0
Period 2 dose change	1	0
Period 2 Physician Decision	1	0
Period 2 Did not meet eligibility criteria	3	0
Period 3 Adverse Event	1	1
Period 3 Withdrawal by Subject	0	2
Period 3 incorrect treatment	0	1
Period 3 Sponsor's withdrawal	0	1

Baseline Characteristics

Efficacy and Safety of SPARC0921 in Subjects With Spasticity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SPARC0921 n=147 Participants SPARC0921 Subjects who received SPARC0921 Dose Regimen I at Visit 1: 392 Received SPARC0921 Dose Regimen II at Visit 2 (Safety Population): 376 Randomized at Visit 7 to receive Dose Regimen III: 147	Placebo0921 n=146 Participants Placebo0921 Randomized at Visit 7: 149	Total n=293 Participants Total of all reporting groups
Age, Continuous	48.8 years STANDARD_DEVIATION 10.39 • n=5 Participants	51.0 years STANDARD_DEVIATION 9.39 • n=7 Participants	49.9 years STANDARD_DEVIATION 9.95 • n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	99 Participants n=7 Participants	204 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	47 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	137 Participants n=5 Participants	136 Participants n=7 Participants	273 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	19 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) White	131 Participants n=5 Participants	122 Participants n=7 Participants	253 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 22

Population: Intent to treat population: SPARC0921, N=147 and and Placebo, N=146

Outcome measures

Outcome measures
Measure	SPARC0921 n=147 Participants SPARC0921	Placebo0921 n=146 Participants Placebo0921
Treatment Failure Rate	36.1 percentage of subjects	43.2 percentage of subjects

SECONDARY outcome

Timeframe: Week 22

Population: Intent to treat population: SPARC0921, N=147 and Placebo0921, N=146

The subject was asked "Overall, how would you rate the severity of your spasticity over the past 24 hours?" The 7-point scale for Subject's global impression of severity assessment is as follows: minimum score of 1 = normal, no spasticity maximum score of 7 (worst outcome)= worst spasticity imaginable

Outcome measures

Outcome measures
Measure	SPARC0921 n=147 Participants SPARC0921	Placebo0921 n=146 Participants Placebo0921
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Normal, no spasticity	19.7 percentage of subjects	10.3 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Borderline spasticity	6.8 percentage of subjects	13 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Mild spasticity	26.5 percentage of subjects	20.5 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Moderate spasticity	27.9 percentage of subjects	33.6 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Marked spasticity	15.0 percentage of subjects	14.4 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Severe spasticity	4.1 percentage of subjects	6.2 percentage of subjects
Severity of Spasticity Assessed by Subject Global Impression Severity Scale Worst spasticity imaginable	0 percentage of subjects	2.1 percentage of subjects

Adverse Events

SPARC0921- Part 3

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo0921 - Part 3

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

SPARC 0921 - Part 2

Serious events: 12 serious events

Other events: 226 other events

Deaths: 1 deaths

Run-in Part 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SPARC0921- Part 3 n=147 participants at risk SPARC0921 in randomized phase	Placebo0921 - Part 3 n=149 participants at risk Placebo0921 in randomized phase	SPARC 0921 - Part 2 n=376 participants at risk Open label	Run-in Part 1 n=392 participants at risk Open label run-in period
Injury, poisoning and procedural complications Hip fracture	0.68% 1/147 • Number of events 1 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Metabolism and nutrition disorders Hypokalaemia	0.68% 1/147 • Number of events 1 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders Syncope	0.68% 1/147 • Number of events 1 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Cardiac disorders Acute myocardial infarction	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
General disorders death	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Infections and infestations Urinary tract infection	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.53% 2/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders Encephalopathy	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Psychiatric disorders Delirium	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Psychiatric disorders Psychotic disorder	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Vascular disorders Deep vein thrombosis	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.27% 1/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.

Other adverse events

Additional Information

SPARC

Sun Pharma Advanced Research Company Limited

Phone: 912266455645

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	SPARC0921- Part 3 n=147 participants at risk SPARC0921 in randomized phase	Placebo0921 - Part 3 n=149 participants at risk Placebo0921 in randomized phase	SPARC 0921 - Part 2 n=376 participants at risk Open label	Run-in Part 1 n=392 participants at risk Open label run-in period
Nervous system disorders Muscle spasticity	9.5% 14/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	10.1% 15/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	7.2% 27/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders Headache	4.1% 6/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 4/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.7% 14/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Infections and infestations Urinary tract infection	2.0% 3/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	4.0% 6/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.2% 12/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Musculoskeletal and connective tissue disorders Muscle spasm	1.4% 2/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 4/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.2% 12/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Investigations Blood pressure increased	0.68% 1/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 4/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	1.3% 5/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
General disorders Fatigue	2.7% 4/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	6.4% 24/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Infections and infestations Nasopharyngitis	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 4/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.5% 13/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Psychiatric disorders Insomnia	0.68% 1/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.0% 3/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.4% 9/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Gastrointestinal disorders Nausea	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	5.9% 22/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders somnolence	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	5.6% 21/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders multiple sclerosis relapse	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.2% 12/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders dizziness	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 10/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Nervous system disorders Tremor	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	1.6% 6/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Gastrointestinal disorders vomitting	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.4% 9/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Infections and infestations sinusitis	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	3.2% 12/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.9% 11/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
General disorders Oedema peripheral	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	2.7% 10/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
General disorders Asthenia	0.00% 0/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.00% 0/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	1.6% 6/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Gastrointestinal disorders Diarrhoea	1.4% 2/147 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	1.3% 2/149 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	1.6% 6/376 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.	0.26% 1/392 • Week 22 Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.