Trial Outcomes & Findings for Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis (NCT NCT03598036)

Results Overview

Complete remission OR Partial remission

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

24 weeks

Results posted on

2021-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	Voclosporin Cohort 1 Cohort 1: Maximum dose of 3 capsules voclosporin (23.7 mg total) twice daily	Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2 Cohort 2: When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily. The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily.
Overall Study STARTED	5	0
Overall Study Week 1: 7.9 mg Twice Daily	5	0
Overall Study Week 2: 15.9 mg Twice Daily	5	0
Overall Study Weeks 3 - 24: 23.7 mg Twice Daily	5	0
Overall Study COMPLETED	4	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Voclosporin Cohort 1 Cohort 1: Maximum dose of 3 capsules voclosporin (23.7 mg total) twice daily	Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2 Cohort 2: When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily. The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 24 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected

Complete remission OR Partial remission

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 8 and 12

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Complete remission or partial remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 8, 12, and 24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Complete remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 8, 12, and 24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Reduction of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 8, 12, and 24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Partial remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Complete OR partial remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Complete remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Partial remission of proteinuria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

50% reduction in Urine Protein Creatinine Ratio (UPCR) from baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Duration of reduced Urine Protein Creatinine Ratio (UPCR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2,4,8,12,18,24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Change from baseline in Urine Protein Creatinine Ratio (UPCR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2,4,8,12,18,24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Utilizing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24 to Week 26

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Increase in Estimated Glomerular Filtration Rate (eGFR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24 and Week 26

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Change in Urine Protein Creatinine Ratio (UPCR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24 and Week 26

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Change in estimated Glomerular Filtration Rate (eGFR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2,4,8,12,18,24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Change from baseline in serum creatinine, serum albumin and estimate Glomerular Filtration Rate (eGFR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Mean change in Patient Reported Outcome Measurement Information System (PROMIS) measures

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Change from baseline in Kidney Disease Quality of Life-Short Form (KDQOL-SF)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Incidence and number of treatment-emergent adverse events

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 weeks

Population: Due to difficulties enrolling appropriate Focal Segmental Glomerulosclerosis (FSGS) patients, Aurinia terminated the clinical trial early. Focal Segmental Glomerulosclerosis (FSGS) is a rare disease with an estimated 40,000 adult patients in the USA. Only five subjects were enrolled into the clinical trial. The primary and secondary endpoints were not assessed due to insufficient data collected.

Descriptive analyses of changes in histopathology will be evaluated in post treatment renal biopsies in a subset of patients

Outcome measures

Outcome data not reported

Adverse Events

Voclosporin Cohort 1: Week 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Voclosporin Cohort 1: Week 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Voclosporin Cohort 1: Weeks 3-24

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Voclosporin Cohort 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Voclosporin Cohort 1: Week 1 n=5 participants at risk Cohort 1: Week 1 7.9 mg twice daily	Voclosporin Cohort 1: Week 2 n=5 participants at risk Cohort 1: Week 2 15.9 mg twice daily	Voclosporin Cohort 1: Weeks 3-24 n=5 participants at risk Cohort 1: Weeks 3-24 23.7 mg twice daily	Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2 Cohort 2: When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily. The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Renal and urinary disorders Acute Kidney Injury	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2

Other adverse events

Additional Information

Clinical Trial Support

Aurinia Pharmaceuticals Inc.

Phone: 1 (250) 744-2487

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Voclosporin Cohort 1 n=5 Participants Cohort 1: Maximum dose of 3 capsules voclosporin (23.7 mg total) twice daily	Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2 Cohort 2: When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily. The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily.	Total n=5 Participants Total of all reporting groups
Age, Continuous	36.2 years STANDARD_DEVIATION 20.71 • n=5 Participants	—	36.2 years STANDARD_DEVIATION 20.71 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	—	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	—	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	—	3 participants n=5 Participants
Region of Enrollment Dominican Republic	2 participants n=5 Participants	—	2 participants n=5 Participants

Measure	Voclosporin Cohort 1: Week 1 n=5 participants at risk Cohort 1: Week 1 7.9 mg twice daily	Voclosporin Cohort 1: Week 2 n=5 participants at risk Cohort 1: Week 2 15.9 mg twice daily	Voclosporin Cohort 1: Weeks 3-24 n=5 participants at risk Cohort 1: Weeks 3-24 23.7 mg twice daily	Voclosporin Cohort 2 Trial ended prematurely before any patients were enrolled into Cohort 2 Cohort 2: When Cohort 1 have completed 12 weeks of treatment with voclosporin, the top line efficacy and safety data will be analyzed to determine the dose level for Cohort 2. The selected dose may be higher or lower than 23.7 mg twice daily. The maximum dose possible for Cohort 2 will be 39.5 mg (5 capsules) twice daily.
Investigations Blood creatine phosphokinase increased	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	40.0% 2/5 • Number of events 2 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Investigations Glomerular filtration rate decreased	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	60.0% 3/5 • Number of events 3 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Nervous system disorders Headache	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	40.0% 2/5 • Number of events 2 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Nervous system disorders Dizziness	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Nervous system disorders Paraesthesia	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Nervous system disorders Tremor	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Gastrointestinal disorders Gingival bleeding	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Gastrointestinal disorders Vomiting	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
General disorders Pyrexia	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 2 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
General disorders Oedema Peripheral	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Infections and infestations Influenza	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Infections and infestations Viral upper respiratory tract infection	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Vascular disorders Hypertension	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Vascular disorders Hypotension	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Endocrine disorders Cushingoid	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Eye disorders Ocular discomfort	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Psychiatric disorders Insomnia	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Renal and urinary disorders Haematuria	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	0.00% 0/5 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	20.0% 1/5 • Number of events 1 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2	— 0/0 • Day 1 to Week 26 Trial ended prematurely before any patients were enrolled into Cohort 2