Trial Outcomes & Findings for Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis (NCT NCT01833754)

Last Updated: 2022-07-22

Results Overview

A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: * fatal * life-threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

From the first dose of study drug up to day 85

Results posted on

2022-07-22

Participant Flow

This study was conducted at 5 centers in the United States. The first participant enrolled on 22 April 2013 and the last participant enrolled on 05 November 2013.

Participant milestones

Participant milestones
Measure	Group 1: Stage 4 Renal Impairment Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Overall Study STARTED	8	8	8
Overall Study COMPLETED	8	8	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Total n=24 Participants Total of all reporting groups
Age, Continuous	66.5 years STANDARD_DEVIATION 8.4 • n=5 Participants	65.1 years STANDARD_DEVIATION 6.7 • n=7 Participants	63.0 years STANDARD_DEVIATION 8.8 • n=5 Participants	64.9 years STANDARD_DEVIATION 7.8 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to day 85

Population: All participants who received study drug

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Number of Participants With Adverse Events Fatal adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events All adverse events	7 Participants	6 Participants	0 Participants
Number of Participants With Adverse Events Serious adverse events	1 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events AEs leading to discontinuation of study drug	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Treatment-related adverse events	5 Participants	6 Participants	0 Participants
Number of Participants With Adverse Events Treatment-related serious adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events TRAEs leading to discontinuation of study drug	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Treatment-related fatal adverse events	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline and day 85

Population: All participants who received study drug

Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Number of Participants Who Developed Anti-Romosozumab Antibodies Binding antibody positive	0 Participants	0 Participants	1 Participants
Number of Participants Who Developed Anti-Romosozumab Antibodies Neutralizing antibody positive	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Population: All participants who received study drug

Albumin-adjusted calcium was derived as: Where serum albumin \< 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 \* \[40 - serum albumin (g/L)\]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Albumin-Adjusted Serum Calcium Concentrations by Visit Baseline	2.452 mmol/L Standard Deviation 0.228	2.379 mmol/L Standard Deviation 0.131	2.340 mmol/L Standard Deviation 0.057
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 8	2.355 mmol/L Standard Deviation 0.187	2.226 mmol/L Standard Deviation 0.205	2.308 mmol/L Standard Deviation 0.072
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 15	2.378 mmol/L Standard Deviation 0.146	2.194 mmol/L Standard Deviation 0.107	2.293 mmol/L Standard Deviation 0.070
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 22	2.329 mmol/L Standard Deviation 0.151	2.074 mmol/L Standard Deviation 0.193	2.311 mmol/L Standard Deviation 0.104
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 29	2.338 mmol/L Standard Deviation 0.162	2.166 mmol/L Standard Deviation 0.258	2.316 mmol/L Standard Deviation 0.062
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 43	2.404 mmol/L Standard Deviation 0.200	2.209 mmol/L Standard Deviation 0.169	2.320 mmol/L Standard Deviation 0.065
Albumin-Adjusted Serum Calcium Concentrations by Visit Day 57	2.406 mmol/L Standard Deviation 0.179	2.284 mmol/L Standard Deviation 0.114	2.319 mmol/L Standard Deviation 0.070
Albumin-Adjusted Serum Calcium Concentrations by Visit End of Study	2.428 mmol/L Standard Deviation 0.201	2.291 mmol/L Standard Deviation 0.264	2.330 mmol/L Standard Deviation 0.065

PRIMARY outcome

Timeframe: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Population: All participants who received study drug and with available data at each time point

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 8	9.192 pmol/L Standard Deviation 3.077	19.812 pmol/L Standard Deviation 16.289	6.776 pmol/L Standard Deviation 3.612
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Baseline	5.014 pmol/L Standard Deviation 1.597	11.765 pmol/L Standard Deviation 12.003	4.682 pmol/L Standard Deviation 3.432
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 15	8.887 pmol/L Standard Deviation 4.743	17.376 pmol/L Standard Deviation 10.108	6.473 pmol/L Standard Deviation 3.880
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 22	10.425 pmol/L Standard Deviation 4.190	29.724 pmol/L Standard Deviation 20.565	6.818 pmol/L Standard Deviation 3.959
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 29	12.495 pmol/L Standard Deviation 5.248	29.857 pmol/L Standard Deviation 20.461	7.348 pmol/L Standard Deviation 3.997
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 43	9.921 pmol/L Standard Deviation 5.906	21.374 pmol/L Standard Deviation 14.184	6.508 pmol/L Standard Deviation 3.289
Intact Parathyroid Hormone (iPTH)Concentrations by Visit Day 57	9.311 pmol/L Standard Deviation 4.571	17.893 pmol/L Standard Deviation 11.196	5.279 pmol/L Standard Deviation 2.215
Intact Parathyroid Hormone (iPTH)Concentrations by Visit End of Study	6.958 pmol/L Standard Deviation 3.812	23.503 pmol/L Standard Deviation 24.339	4.457 pmol/L Standard Deviation 2.506

SECONDARY outcome

Timeframe: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Population: All participants were included in the analysis

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Maximum Observed Serum Concentration (Cmax) of Romosozumab	28.9 µg/mL Standard Deviation 10.8	19.8 µg/mL Standard Deviation 7.3	22.4 µg/mL Standard Deviation 10.3

SECONDARY outcome

Timeframe: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Population: All participants were included in the analysis

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab	5.0 days Full Range 10.8 • Interval 3.0 to 7.0	5.0 days Full Range 7.3 • Interval 3.0 to 7.0	5.0 days Full Range 10.3 • Interval 3.0 to 7.0

SECONDARY outcome

Timeframe: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Population: All participants were included in the analysis

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	637 days*µg/mL Standard Deviation 218	444 days*µg/mL Standard Deviation 154	443 days*µg/mL Standard Deviation 143

SECONDARY outcome

Timeframe: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Population: All participants were included in the analysis

Outcome measures

Outcome measures
Measure	Group 1: Stage 4 Renal Impairment n=8 Participants Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 Participants Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)	642 days*µg/mL Standard Deviation 221	447 days*µg/mL Standard Deviation 154	445 days*µg/mL Standard Deviation 143

Adverse Events

Group 1: Stage 4 Renal Impairment

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Group 2: ESRD Requiring Hemodialysis

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Group 3: Healthy Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1: Stage 4 Renal Impairment n=8 participants at risk Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 participants at risk Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 participants at risk Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Blood and lymphatic system disorders Anaemia	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Mitral valve disease	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group 1: Stage 4 Renal Impairment n=8 participants at risk Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 2: ESRD Requiring Hemodialysis n=8 participants at risk Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Group 3: Healthy Participants n=8 participants at risk Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
Cardiac disorders Atrial fibrillation	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Hyperparathyroidism	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Hyperparathyroidism secondary	50.0% 4/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	25.0% 2/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastritis	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrooesophageal reflux disease	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gingival recession	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Haemorrhoids	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Large intestine polyp	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Injection site pruritus	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Post procedural haematoma	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Wound	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood creatinine increased	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Glomerular filtration rate decreased	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Heart rate increased	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Gout	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 4/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Sciatica	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Wheezing	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 1/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/8 • From the first dose of study drug up to day 85. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.