Trial Outcomes & Findings for LEO 90100 Twice Weekly Maintenance Regimen for Psoriasis Vulgaris (NCT NCT02899962)

Last Updated: 2020-08-20

Results Overview

Time to first relapse (at least 'mild' according to the Physician's Global Assessment of disease severity \[PGA\]). The investigator was to grade the severity of psoriasis of the trunk and limbs using Physician's global assessment of disease severity 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

722 participants

Primary outcome timeframe

From Randomisation (Week 4) until first relapse or End of Treatment (Week 56 or early withdrawal)

Results posted on

2020-08-20

Participant Flow

722 subjects were screened of which 650 subjects were assigned to treatment with LEO 90100 open-label phase. Subjects did not progress from screening due to adverse event=1, lost to follow-up=2, other reasons=2, screening failures=52, and withdrawal by subject=15. All 650 subjects were exposed to LEO 90100 during the open-label phase

Participant milestones

Participant milestones
Measure	Open-label LEO 90100 In the open-label phase, LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks.	Maintenance LEO 90100 In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive LEO 90100 twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks.	Maintenance Vehicle In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive vehicle twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks.
Open-label Phase STARTED	650	0	0
Open-label Phase COMPLETED	623	0	0
Open-label Phase NOT COMPLETED	27	0	0
Maintenance Phase STARTED	0	272	273
Maintenance Phase COMPLETED	0	131	120
Maintenance Phase NOT COMPLETED	0	141	153

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label LEO 90100 In the open-label phase, LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks.	Maintenance LEO 90100 In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive LEO 90100 twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks.	Maintenance Vehicle In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive vehicle twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks.
Open-label Phase Adverse Event	2	0	0
Open-label Phase Lost to Follow-up	9	0	0
Open-label Phase Other reasons	9	0	0
Open-label Phase Withdrawal by Subject	7	0	0
Maintenance Phase Adverse Event	0	2	1
Maintenance Phase Death	0	0	1
Maintenance Phase Lack of Efficacy	0	20	16
Maintenance Phase Lost to Follow-up	0	12	14
Maintenance Phase Other reasons	0	9	13
Maintenance Phase Not achieve treatment success after Wk 4	0	3	2
Maintenance Phase Not clear/almost clear after rescue med	0	65	70
Maintenance Phase Withdrawal by Subject	0	30	36

Baseline Characteristics

Data available only from 635 subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LEO 90100 Open-label Phase n=650 Participants LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks.
Age, Continuous	51.8 Years STANDARD_DEVIATION 14.2 • n=650 Participants
Sex: Female, Male Female	226 Participants n=650 Participants
Sex: Female, Male Male	424 Participants n=650 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	75 Participants n=650 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	568 Participants n=650 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=650 Participants
Race/Ethnicity, Customized Race · White	584 Participants n=635 Participants • Data available only from 635 subjects
Race/Ethnicity, Customized Race · Asian	37 Participants n=635 Participants • Data available only from 635 subjects
Race/Ethnicity, Customized Race · Black or African American	9 Participants n=635 Participants • Data available only from 635 subjects
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	4 Participants n=635 Participants • Data available only from 635 subjects
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=635 Participants • Data available only from 635 subjects
Region of Enrollment Canada	163 participants n=650 Participants
Region of Enrollment United States	228 participants n=650 Participants
Region of Enrollment Poland	60 participants n=650 Participants
Region of Enrollment United Kingdom	79 participants n=650 Participants
Region of Enrollment France	61 participants n=650 Participants
Region of Enrollment Germany	59 participants n=650 Participants
PGA Mild	83 Participants n=650 Participants
PGA Moderate	509 Participants n=650 Participants
PGA Severe	58 Participants n=650 Participants

PRIMARY outcome

Timeframe: From Randomisation (Week 4) until first relapse or End of Treatment (Week 56 or early withdrawal)

Population: Full analysis set: included all subjects randomised who had treatment success at randomisation, defined as PGA score of 'clear' or 'almost clear' with at least a 2-grade improvement from baseline

Outcome measures

Outcome measures
Measure	LEO 90100 Aerosol Foam n=256 Participants Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks	LEO 90100 Aerosol Foam Vehicle n=265 Participants Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Time to First Relapse	56 days Interval 34.0 to 59.0	30 days Interval 29.0 to 31.0

SECONDARY outcome

Timeframe: From Randomisation (Week 4) until End of Treatment (Week 56 or early withdrawal)

Remission defined as 'clear' or 'almost clear' according to the PGA. The investigator was to grade using a global assessment of the disease severity of psoriasis of the trunk and limbs using the PGA 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4

Outcome measures

Outcome measures
Measure	LEO 90100 Aerosol Foam n=256 Participants Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks	LEO 90100 Aerosol Foam Vehicle n=265 Participants Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Proportion of Days in Remission During the Maintenance Phase	70.2 Proportion of days Standard Deviation 21.7	60.8 Proportion of days Standard Deviation 20.1

SECONDARY outcome

Timeframe: From Randomisation (Week 4) until End of Treatment (Week 56)

Defined as number of 4-week periods with use of once-daily rescue investigational medicinal product

Outcome measures

Outcome measures
Measure	LEO 90100 Aerosol Foam n=256 Participants Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks	LEO 90100 Aerosol Foam Vehicle n=265 Participants Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Number of Relapses During the Maintenance Phase	2.0 relapses Standard Deviation 1.7	3.1 relapses Standard Deviation 2.2

Adverse Events

LEO 90100 Aerosol Foam Open-label

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

LEO 90100 Aerosol Foam

Serious events: 14 serious events

Other events: 83 other events

Deaths: 0 deaths

LEO 90100 Aerosol Foam Vehicle

Serious events: 11 serious events

Other events: 87 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Disclosure Specialist

LEO Pharma A/S

Phone: +45 44945888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee LEO Pharma acknowledges the investigators' right to publish the entire results of the study, irrespective of outcome. LEO Pharma retains the right to have any publication submitted to LEO Pharma for review. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO Pharma.
Publication restrictions are in place

Restriction type: OTHER

Measure	LEO 90100 Aerosol Foam Open-label n=650 participants at risk Topical application once daily for 4 weeks LEO 90100 aerosol foam open-label	LEO 90100 Aerosol Foam n=272 participants at risk Topical application twice weekly for 52 weeks LEO 90100 aerosol foam: LEO 90100 aerosol foam twice weekly	LEO 90100 Aerosol Foam Vehicle n=273 participants at risk Topical application twice weekly for 52 weeks LEO 90100 aerosol foam vehicle: LEO 90100 aerosol foam vehicle twice weekly
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.15% 1/650 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Injury, poisoning and procedural complications Intentional overdose	0.15% 1/650 • Number of events 2 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 4 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Musculoskeletal and connective tissue disorders Myositis	0.15% 1/650 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Nervous system disorders Cerebrovascular accident	0.15% 1/650 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Cardiac disorders Myocardial ischaemia	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Cardiac disorders Coronary artery occlusion	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Cardiac disorders Acute myocardial infarction	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Cardiac disorders Atrial fibrillation	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Cardiac disorders Mitral valve incompetence	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Vascular disorders Arterial stenosis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.74% 2/272 • Number of events 2 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Vascular disorders Hypertension	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Vascular disorders Venous thrombosis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Infections and infestations Pneumonia	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Infections and infestations Atypical pneumonia	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Infections and infestations Appendicitis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Infections and infestations Endocarditis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Gastrointestinal disorders Alcoholic pancreatitis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Gastrointestinal disorders Colitis	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/272 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/273 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Immune system disorders Drug hypersensitivity	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Ear and labyrinth disorders Vertigo	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
General disorders Chest pain	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/650 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.37% 1/272 • Number of events 1 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded	0.00% 0/273 • 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up All adverse events were reported by the subjects or observed by the investigators were recorded