Trial Outcomes & Findings for Phase 3 Study of SNF472 for Calciphylaxis (NCT NCT04195906)

NCT ID: NCT04195906

Last Updated: 2024-02-20

Results Overview

The Bates Jensen Wound Assessment Tool (BWAT) CUA score ranges from a minimum score of 8 (best) to a maximum score of 40 (worst). BWAT-CUA= Bates-Jensen Wound Assessment Tool-Calcific Uremic Arteriolopathy

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

71 participants

Primary outcome timeframe

from Baseline to Week 12

Results posted on

2024-02-20

Participant Flow

A total of 148 participants were screened in 48 sites in 5 countries; 77 participants were not enrolled because they were screen failures (did not meet eligibility criteria). A total of 71 participants were randomized in the study to receive SNF472 or placebo.

Participant milestones

Participant milestones
Measure	SNF472 (Double-blind Period + Open-label) Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks. Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.	Placebo (Double-blind Period) + SNF472 (Open-label) Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care. Dose: Matching placebo (saline) diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.
Part 1 STARTED	37	34
Part 1 COMPLETED	34	26
Part 1 NOT COMPLETED	3	8
Part 2 STARTED	34	26
Part 2 COMPLETED	32	19
Part 2 NOT COMPLETED	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	SNF472 (Double-blind Period + Open-label) Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks. Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.	Placebo (Double-blind Period) + SNF472 (Open-label) Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care. Dose: Matching placebo (saline) diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.
Part 1 Adverse Event	3	7
Part 1 Withdrawal by Subject	0	1
Part 2 Adverse Event	1	1
Part 2 Withdrawal by Subject	0	3
Part 2 Other	1	3

Baseline Characteristics

Phase 3 Study of SNF472 for Calciphylaxis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SNF472 n=37 Participants Part 1 (double-blind period): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks. Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.	Placebo n=34 Participants Part 1 (double-blind period) Participants received placebo for 12 weeks in addition to their background care. Dose: Matching placebo (saline) diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks. Part 2 (Open-label): Participants received SNF472 for 12 weeks in addition to their background care. Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks.	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Age, Continuous	57.7 years STANDARD_DEVIATION 12.14 • n=5 Participants	57.2 years STANDARD_DEVIATION 11.30 • n=7 Participants	57.5 years STANDARD_DEVIATION 11.66 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	31 Participants n=7 Participants	62 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Europe	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment North America	32 participants n=5 Participants	32 participants n=7 Participants	64 participants n=5 Participants

PRIMARY outcome

Timeframe: from Baseline to Week 12

Population: Modified Intent-to-treat Population (mITT) population: defined as all enrolled subjects who were randomized, received at least one dose of study drug, and had at least one post-randomization efficacy evaluation.

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Absolute Change in the BWAT - CUA Score for the Primary Lesion	-5.3 score on a scale Standard Deviation 5.18	-6.0 score on a scale Standard Deviation 6.17

PRIMARY outcome

Timeframe: from Baseline to Week 12

The Pain Visual Analog Scale (VAS) score ranges from a minimum score of 0 (no pain) to 100 (worst possible pain).

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Absolute Change in Pain Visual Analog Score	-19.5 score on a scale Standard Deviation 26.89	-32.2 score on a scale Standard Deviation 38.53

SECONDARY outcome

Timeframe: from Baseline to Week 12

The Wound Quality of Life scale is a validated self-assessment tool that has been shown to be feasible for assessing health-related quality of life in patients with chronic wounds. Lower scores are associated with a better quality of life as reported by the patient. The score is computed by averaging the 17 items on impairments assessed on a scale of 0 to 4 for the preceding 7 days. A global score can only be computed if at least 75% of the items have been answered, i.e., at least 13 in 17 items are valid. All the available items' scores were added up and divided by 17. In case of missing assessments for any one of the 17 items, the median of the scores for a particular item within the associated randomized treatment group was used for the imputation purposes. As the absolute change from baseline is reported, a higher negative value is associated with a higher improvement of quality of life.

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Absolute Change in the Wound-Quality of Life Score	-0.67 score on a scale Standard Deviation 0.798	-0.74 score on a scale Standard Deviation 1.175

SECONDARY outcome

Timeframe: from Baseline to Week 12

The Bates Jensen Wound Assessment Tool (BWAT) score ranges from a minimum score of 9 (best) to a maximum score of 65 (worst) score.

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Absolute Change in the BWAT Total Score for the Primary Lesion	-11.0 score on a scale Standard Deviation 9.85	-11.7 score on a scale Standard Deviation 12.23

SECONDARY outcome

Timeframe: at Week 12

A qualitative assessment (Worsened, Equal to, or Improved Relative to Baseline) was assigned

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Qualitative Wound Image Evaluation for the Primary Lesion Worsened	6 Participants	7 Participants
Qualitative Wound Image Evaluation for the Primary Lesion Equal	0 Participants	1 Participants
Qualitative Wound Image Evaluation for the Primary Lesion Improved	23 Participants	18 Participants
Qualitative Wound Image Evaluation for the Primary Lesion Missing	8 Participants	8 Participants

SECONDARY outcome

Timeframe: from Baseline to Week 12

Change from baseline in opioid use MME = Morphine Milligram Equivalents The calculation of the pre-specified list of opioids was based on the formula: strength per unit × (number of units/days supply) × MME conversion factor = MME/day, as specified in the opioid MME conversion guide (CMS, 2017). The maintenance opioid dose was defined as the average daily opioid dose in MME during the 7-day period prior to Screening Visit 2. To assess the extent to which opioid use may have differed between randomized treatment groups over time, the change from baseline in daily average MME value was analyzed.

Outcome measures

Outcome measures
Measure	SNF472 n=37 Participants Participants who received SNF472 for 12 weeks in addition to their background care during the double-blind period (Part 1). Dose: 7 mg/kg SNF472 diluted in 100 mL physiological saline. Experimental: SNF472: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions for 12 weeks	Placebo n=34 Participants Participants who received placebo for 12 weeks in addition to their background care during the double-blind period (Part 1). Matching placebo (saline) diluted in 100 mL physiological saline. Placebo Comparator: Placebo: Administered 3 times weekly by intravenous infusion through the hemodialysis machine in conjunction with the subject's hemodialysis sessions fo 12 weeks
Rate of Change in Opioid Use as Measured in Morphine Milligram Equivalents (MME)	0.46 MME/week Standard Error 0.461	-0.11 MME/week Standard Error 0.499

Adverse Events

SNF472 - Safety Analysis Population (Part 1)

Serious events: 13 serious events

Other events: 27 other events

Deaths: 1 deaths

Placebo - Safety Analysis Population (Part 1)

Serious events: 17 serious events

Other events: 21 other events

Deaths: 6 deaths

SNF472 Open Label - Safety Analysis Population (Part 2)

Serious events: 18 serious events

Other events: 33 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Peter Szecsödy

Sanifit Therapeutics S. A.

Phone: +41588529079

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	SNF472 - Safety Analysis Population (Part 1) n=38 participants at risk Participants who received SNF472 treatment during part 1 (Double-blind Period). The number of participants in the safety set differs from the previous figures provided in the Participant Flow section, as 1 participant associated to placebo arm, by mistake, actually received a few infusions with SNF472. As a consequence, this participant is counted within the SNF472 Safety Analysis Population (making it 38 subjects instead of 37).	Placebo - Safety Analysis Population (Part 1) n=33 participants at risk Participants who received placebo during part 1 (Double-blind Period).	SNF472 Open Label - Safety Analysis Population (Part 2) n=60 participants at risk Participants who received SNF472 treatment during part 2 (Open-label)
Metabolism and nutrition disorders Calciphylaxis	21.1% 8/38 • Number of events 9 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	24.2% 8/33 • Number of events 9 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.7% 4/60 • Number of events 8 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Infections and infestations Cellulitis	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Musculoskeletal and connective tissue disorders Pain in extremity	10.5% 4/38 • Number of events 4 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	8.3% 5/60 • Number of events 5 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Nervous system disorders Headache	7.9% 3/38 • Number of events 3 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	9.1% 3/33 • Number of events 5 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Gastrointestinal disorders Nausea	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	12.1% 4/33 • Number of events 4 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	5.0% 3/60 • Number of events 3 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Gastrointestinal disorders Vomiting	13.2% 5/38 • Number of events 6 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.3% 2/60 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Musculoskeletal and connective tissue disorders Arthralgia	13.2% 5/38 • Number of events 6 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Injury, poisoning and procedural complications Fall	7.9% 3/38 • Number of events 3 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	8.3% 5/60 • Number of events 5 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Cardiac disorders Atrial fibrillation	5.3% 2/38 • Number of events 5 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Infections and infestations COVID-19	2.6% 1/38 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Metabolism and nutrition disorders Hypervolemia	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Blood and lymphatic system disorders Anaemia	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.3% 2/60 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Gastrointestinal disorders Diarrhoea	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	8.3% 5/60 • Number of events 5 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
General disorders Pyrexia	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	1.7% 1/60 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Musculoskeletal and connective tissue disorders Back pain	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.3% 2/60 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Metabolism and nutrition disorders Hyperkalaemia	2.6% 1/38 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.0% 1/33 • Number of events 1 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.7% 4/60 • Number of events 4 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Vascular disorders Hypertension	0.00% 0/38 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	5.0% 3/60 • Number of events 3 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Metabolism and nutrition disorders Hypokalaemia	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Musculoskeletal and connective tissue disorders Muscular weakness	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/38 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/38 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Injury, poisoning and procedural complications Vascular access malfunction	0.00% 0/38 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	3.3% 2/60 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Cardiac disorders Ventricular tachycardia	0.00% 0/38 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
Metabolism and nutrition disorders Decreased appetite	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/33 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	0.00% 0/60 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.
General disorders Pain	5.3% 2/38 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	6.1% 2/33 • Number of events 2 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.	5.0% 3/60 • Number of events 4 • Part 1: 12-week double-blind, randomized, placebo-controlled treatment period Part 2: 12-week open-label treatment period after completion of part 1 period.