Trial Outcomes & Findings for Efficacy and Safety of 6 Months Treatment With Paricalcitol Injection or Oral in Patients With Secondary Hyperparathyroidism on Dialysis (NCT NCT00537979)

Last Updated: 2011-10-25

Results Overview

Number of participants who achieved at least a 50% reduction in intact parathyroid hormone (iPTH) compared to the baseline level.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

147 participants

Primary outcome timeframe

24 weeks

Results posted on

2011-10-25

Participant Flow

Participants were enrolled into the study at 12 dialysis centers in Mexico. Recruitment began in September 2007 and ended in January 2010. The study population consisted of patients on hemodialysis or peritoneal dialysis with a diagnosis of secondary hyperparathyroidism.

Participant milestones

Participant milestones
Measure	Paricalcitol Injection Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Overall Study STARTED	38	109
Overall Study COMPLETED	32	89
Overall Study NOT COMPLETED	6	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Paricalcitol Injection Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	1	4
Overall Study Lost to Follow-up	1	4
Overall Study Lack of Efficacy	0	1
Overall Study Non-compliance with treatment/procedure	2	2
Overall Study Death	0	3
Overall Study Kidney transplant	0	3
Overall Study Heart failure	0	1

Baseline Characteristics

Efficacy and Safety of 6 Months Treatment With Paricalcitol Injection or Oral in Patients With Secondary Hyperparathyroidism on Dialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paricalcitol Injection n=38 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 Participants Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.	Total n=147 Participants Total of all reporting groups
Age Continuous	43.79 years STANDARD_DEVIATION 16.36 • n=5 Participants	44.89 years STANDARD_DEVIATION 17.91 • n=7 Participants	44.39 years STANDARD_DEVIATION 17.47 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	50 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	59 Participants n=7 Participants	76 Participants n=5 Participants
Region of Enrollment Mexico	38 participants n=5 Participants	109 participants n=7 Participants	147 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: The analysis was intention to treat (ITT). The ITT population was defined as all participants who fulfilled inclusion criteria and received at least one dose of paricalcitol.

Number of participants who achieved at least a 50% reduction in intact parathyroid hormone (iPTH) compared to the baseline level.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=38 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 Participants Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Proportion of Subjects Who Achieve at Least a 50% Reduction in iPTH Compared to Baseline Level	17 participants	57 participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: The analysis was intention to treat (ITT). The ITT population was defined as all participants who fulfilled inclusion criteria and received at least one dose of paricalcitol.

Number of participants with hypercalcemia (calcium levels greater than 11.5 mg/dL), hyperphosphatemia (phosphorus levels greater than 7.0 mg/dL), or calcium x phosphorus product levels greater than 75.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=38 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 Participants Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Analysis of Episodes of Hypercalcemia (> 11.5 mg/dL), Hyperphosphatemia (> 7.0 mg/dL) and Elevations of Calcium x Phosphorus Product (> 75) Hypercalcemia	2 participants	6 participants
Analysis of Episodes of Hypercalcemia (> 11.5 mg/dL), Hyperphosphatemia (> 7.0 mg/dL) and Elevations of Calcium x Phosphorus Product (> 75) Hyperphosphatemia	9 participants	19 participants
Analysis of Episodes of Hypercalcemia (> 11.5 mg/dL), Hyperphosphatemia (> 7.0 mg/dL) and Elevations of Calcium x Phosphorus Product (> 75) Elevated calcium x phosphorus product	3 participants	14 participants

SECONDARY outcome

Timeframe: 24 weeks

Population: The analysis was intention to treat (ITT). The ITT population was defined as all participants who fulfilled inclusion criteria and received at least one dose of paricalcitol.

Number of participants who achieved an intact parathyroid hormone (iPTH) level of less than 300 pg/mL.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=38 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 Participants Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Proportion of Subjects Who Achieve an iPTH <300 pg/mL	16 participants	57 participants

SECONDARY outcome

Timeframe: 24 weeks

Population: The analysis was per protocol. The per-protocol population was defined as all participants who fulfilled inclusion criteria, had intact parathyroid hormone (iPTH) values greater than or equal to 300 pg/mL at baseline, and completed the study with a final iPTH determination. The per-protocol population included 121 participants.

Number of days required to achieve a reduction in intact parathyroid hormone (iPTH) to less than 300 pg/mL, a reduction in iPTH of greater than or equal to 50%, or either a reduction in iPTH to less than 300 pg/mL or a reduction in iPTH of greater than or equal to 50%.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=121 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Time Required to Achieve: (1) a Reduction in iPTH Less Than <300 pg/mL;(2) a 50% Reduction in iPTH Compared to the Baseline Level; and (3) Either a Reduction in iPTH Less Than <300 pg/mL or a 50% Reduction in iPTH Compared to the Baseline Level Time to achieve iPTH less than 300 pg/mL	43.80 days Standard Deviation 41.43	—
Time Required to Achieve: (1) a Reduction in iPTH Less Than <300 pg/mL;(2) a 50% Reduction in iPTH Compared to the Baseline Level; and (3) Either a Reduction in iPTH Less Than <300 pg/mL or a 50% Reduction in iPTH Compared to the Baseline Level Time to achieve 50% or greater reduction in iPTH	48.68 days Standard Deviation 43.30	—
Time Required to Achieve: (1) a Reduction in iPTH Less Than <300 pg/mL;(2) a 50% Reduction in iPTH Compared to the Baseline Level; and (3) Either a Reduction in iPTH Less Than <300 pg/mL or a 50% Reduction in iPTH Compared to the Baseline Level Time to achieve either	40.29 days Standard Deviation 38.13	—

SECONDARY outcome

Timeframe: 24 weeks

Time in days between 2 consecutive visits with a reduction in intact parathyroid hormone (iPTH) of greater than or equal to 50% from the baseline visit.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=121 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Duration of Response to Treatment	65.86 days Standard Deviation 51.39	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Analysis of the differences before and after 24 weeks of treatment in various quality of life measurements for participants on hemodialysis receiving paricalcitol injection and participants on peritoneal dialysis receiving paricalcitol capsules.

Outcome measures

Outcome measures
Measure	Paricalcitol Injection n=32 Participants Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=89 Participants Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Final Score 3	0 Participants	0 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Baseline Score 1	13 Participants	38 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Baseline Score 2	19 Participants	47 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Baseline Score 3	0 Participants	2 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Final Score 1	23 Participants	74 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Final Score 2	7 Participants	14 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Mobility-Final Score 3	0 Participants	0 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Baseline Score 1	21 Participants	64 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Baseline Score 2	11 Participants	21 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Baseline Score 3	0 Participants	2 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Final Score 1	26 Participants	79 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Final Score 2	4 Participants	9 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Personal Care-Final Score 3	0 Participants	0 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Baseline Score 1	17 Participants	35 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Baseline Score 2	15 Participants	50 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Baseline Score 3	0 Participants	3 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Final Score 1	26 Participants	71 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Final Score 2	4 Participants	16 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Daily Activities-Final Score 3	0 Participants	1 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Baseline Score 1	7 Participants	24 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Baseline Score 2	24 Participants	55 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Baseline Score 3	1 Participants	8 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Final Score 1	25 Participants	73 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Final Score 2	5 Participants	15 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Pain/Discomfort-Final Score 3	0 Participants	0 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Baseline Score 1	25 Participants	34 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Baseline Score 2	7 Participants	48 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Baseline Score 3	0 Participants	6 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Final Score 1	26 Participants	73 Participants
Health-related Quality of Life With Paricalcitol Injection or Oral Treatment Anxiety/Depression-Final Score 2	4 Participants	15 Participants

Adverse Events

Paricalcitol Injection

Serious events: 8 serious events

Other events: 25 other events

Deaths: 0 deaths

Paricalcitol Capsules

Serious events: 9 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Paricalcitol Injection n=38 participants at risk Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 participants at risk Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Gastrointestinal disorders Hernia	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Peritonitis	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Pneumonia	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyperphosphataemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Nervous system disorders Headache	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Nervous system disorders Convulsion	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchitis	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Surgical and medical procedures Indwelling catheter management	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Vascular disorders Hypertension	7.9% 3/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Vascular disorders Hypotension	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.

Other adverse events

Additional Information

Global Medical Services

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Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Paricalcitol Injection n=38 participants at risk Paricalcitol (ABT-358 Zemplar) Injection was administered to participants on hemodialysis.	Paricalcitol Capsules n=109 participants at risk Paricalcitol (ABT-358 Zemplar) capsules were administered to participants on peritoneal dialysis.
Blood and lymphatic system disorders Anaemia	7.9% 3/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Blood and lymphatic system disorders Eosinophilia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Cardiac disorders Tachycardia paroxysmal	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Cardiac disorders Extrasystoles	5.3% 2/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Cardiac disorders Supraventricular tachycardia	5.3% 2/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Cardiac disorders Angina pectoris	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Endocrine disorders Hyperparathyroidism	34.2% 13/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	28.4% 31/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Endocrine disorders Hypoparathyroidism	26.3% 10/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	32.1% 35/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Endocrine disorders Hypothyroidism	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Eye disorders Ocular hyperaemia	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Eye disorders Vision blurred	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Diarrhoea	21.1% 8/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Gastritis	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Vomiting	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Gingivitis	7.9% 3/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Gastrointestinal disorders Nausea	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
General disorders Pyrexia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
General disorders Fatigue	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
General disorders Chest pain	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
General disorders Headache	15.8% 6/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Hepatobiliary disorders Hepatitis	13.2% 5/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Upper respiratory tract infection	7.9% 3/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Ear infection	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Catheter site infection	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	4.6% 5/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Peritonitis	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Herpes zoster	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Unevaluable event	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Dengue fever	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Urinary tract infection	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Infections and infestations Onychomycosis	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Injury, poisoning and procedural complications Incisional hernia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Injury, poisoning and procedural complications Phlebitis	18.4% 7/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	21.1% 8/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	33.9% 37/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	7.9% 3/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyperphosphataemia	63.2% 24/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	63.3% 69/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	13.2% 5/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	4.6% 5/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypertriglyceridaemia	10.5% 4/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	3.7% 4/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	13.2% 5/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	9.2% 10/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	5.3% 2/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Oedema	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	10.5% 4/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	1.8% 2/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Joint dislocation	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	2.8% 3/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Nervous system disorders Dizziness	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Psychiatric disorders Insomnia	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Psychiatric disorders Depression	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Psychiatric disorders Anxiety	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.00% 0/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	3.7% 4/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders Acne	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Surgical and medical procedures Indwelling catheter management	0.00% 0/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	0.92% 1/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Vascular disorders Hypertension	10.5% 4/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	6.4% 7/109 • From date of first dose of study drug through 30 days after the last dose of study drug.
Vascular disorders Hypotension	23.7% 9/38 • From date of first dose of study drug through 30 days after the last dose of study drug.	3.7% 4/109 • From date of first dose of study drug through 30 days after the last dose of study drug.