Trial Outcomes & Findings for Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates (NCT NCT00104650)

NCT ID: NCT00104650

Last Updated: 2011-01-24

Results Overview

Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) \< 50 nmol/mmol at week 13.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

111 participants

Primary outcome timeframe

13 weeks

Results posted on

2011-01-24

Participant Flow

Participants were enrolled from 2 December 2004 through 30 March 2007

Participant milestones

Participant milestones
Measure	Bisphosphonate IV Q4W Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Treatment Period (25 Weeks) STARTED	37	36	38
Treatment Period (25 Weeks) Received Investigational Product	35	35	38
Treatment Period (25 Weeks) COMPLETED	25	25	28
Treatment Period (25 Weeks) NOT COMPLETED	12	11	10
Follow-up Period STARTED	25	25	28
Follow-up Period COMPLETED	14	12	18
Follow-up Period NOT COMPLETED	11	13	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Bisphosphonate IV Q4W Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Treatment Period (25 Weeks) Physician Decision	0	0	1
Treatment Period (25 Weeks) Withdrawal by Subject	2	1	1
Treatment Period (25 Weeks) Death	7	5	6
Treatment Period (25 Weeks) Disease progression	2	3	2
Treatment Period (25 Weeks) Ineligibility determined	0	1	0
Treatment Period (25 Weeks) Other	1	0	0
Treatment Period (25 Weeks) Protocol deviation	0	1	0
Follow-up Period Physician Decision	1	1	0
Follow-up Period Adverse Event	1	0	1
Follow-up Period Withdrawal by Subject	0	3	3
Follow-up Period Death	6	6	4
Follow-up Period Disease progression	3	1	0
Follow-up Period Lost to Follow-up	0	1	2
Follow-up Period Other	0	1	0

Baseline Characteristics

Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Denosumab 180 mg Q4W n=38 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)	Bisphosphonate IV Q4W n=37 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Total n=111 Participants Total of all reporting groups
Age Continuous	60.6 Years STANDARD_DEVIATION 10.7 • n=5 Participants	61.6 Years STANDARD_DEVIATION 11.7 • n=7 Participants	65.3 Years STANDARD_DEVIATION 12.7 • n=5 Participants	62.5 Years STANDARD_DEVIATION 11.8 • n=4 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	56 Participants n=4 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants
Race/Ethnicity, Customized White or Caucasian	22 Participants n=5 Participants	22 Participants n=7 Participants	19 Participants n=5 Participants	63 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	44 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Type Stratification Factor Breast cancer	16 Participants n=5 Participants	16 Participants n=7 Participants	14 Participants n=5 Participants	46 Participants n=4 Participants
Cancer Type Stratification Factor Prostate cancer	17 Participants n=5 Participants	17 Participants n=7 Participants	16 Participants n=5 Participants	50 Participants n=4 Participants
Cancer Type Stratification Factor Mutiple myeloma	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Cancer Type Stratification Factor Other solid tumor	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Urinary N-telopeptide (uNTx) Level	149.94 nmol/mmol STANDARD_DEVIATION 147.20 • n=5 Participants	149.88 nmol/mmol STANDARD_DEVIATION 176.28 • n=7 Participants	175.15 nmol/mmol STANDARD_DEVIATION 208.87 • n=5 Participants	158.01 nmol/mmol STANDARD_DEVIATION 177.11 • n=4 Participants
Serum C-Telopeptide (CTx)	1.12 ng/mL STANDARD_DEVIATION 1.18 • n=5 Participants	1.40 ng/mL STANDARD_DEVIATION 1.93 • n=7 Participants	1.34 ng/mL STANDARD_DEVIATION 1.27 • n=5 Participants	1.28 ng/mL STANDARD_DEVIATION 1.48 • n=4 Participants

PRIMARY outcome

Timeframe: 13 weeks

Population: All participants who are randomized to the treatment phase, receive at least one dose of treatment phase investigational product, and have treatment phase baseline measurements of uNTx and at least one treatment phase post-baseline measurement of uNTx.

Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) \< 50 nmol/mmol at week 13.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=33 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13	10 Participants	21 Participants	28 Participants

SECONDARY outcome

Timeframe: 25 weeks

Urinary N-telopeptide (uNTX) corrected by creatinine \< 50 nmol/mmol at week 25.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=33 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25	13 Participants	21 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline, week 25

Percent change from baseline to week 25 urinary N-telopeptide (uNTX) calculated using ((week 25 value - baseline value) / baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=23 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=25 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=26 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25	-32.91 Percent change Standard Deviation 65.91	-69.09 Percent change Standard Deviation 29.97	-41.68 Percent change Standard Deviation 118.32

SECONDARY outcome

Timeframe: Day 1, week 25

Kaplan-Meier estimate of the median time from enrollment to the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) up to week 25. For participants whose uNTx does not go below 50 nM BCE/mM creatinine, the time is censored at time of last evaluation of uNTx by week 25.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=33 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol	65 Days Interval 8.0 to 141.0	9 Days Interval 4.0 to 11.0	10 Days Interval 8.0 to 11.0

SECONDARY outcome

Timeframe: Day 1, week 25

Population: Treatment Phase Primary Analysis Subset. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject whose uNTX (corrected by creatinine) less than 50nmol/mmol is presented.

Time from the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) to the 1st occurrence of uNTx above 50 nmol BCE/mmol up to week 25. For participants who remained below 50 nmol BCE/mmol, the time is censored at the time of last evaluation of uNTx up to week 25.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=33 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol	25 Participants	32 Participants	35 Participants

SECONDARY outcome

Timeframe: Baseline, week 25

Percent change from baseline to week 25 in Type I serum C-Telopeptide (CTX), calculated using ((week 25 value - baseline value) / baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=23 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=25 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=26 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Percent Change of Serum CTX From Baseline to Week 25	-40.68 Percent change Standard Deviation 38.93	-76.74 Percent change Standard Deviation 19.74	-68.39 Percent change Standard Deviation 36.15

SECONDARY outcome

Timeframe: Day 1, week 25

Population: All participants exposed to investigational product during the treatment phase. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject who experienced a skeletal related event is presented.

Time from study day 1 to first Skeletal Related Event (SRE), defined as \>1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=35 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=38 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Time to First Skeletal Related Event	6 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1, week 25

Population: All participants exposed to investigational product during the treatment phase.

Skeletal Related Event (SRE), defined as \>1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=35 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=38 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Skeletal Related Events	6 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1, week 25

Occurrence of hypercalcemia at grade 3 or 4 according to CTCAE v3 criteria

Outcome measures

Outcome measures
Measure	Bisphosphonate IV Q4W n=35 Participants Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)	Denosumab 180 mg Q12W n=33 Participants Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)	Denosumab 180 mg Q4W n=36 Participants Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Hypercalcemia	0 Participants	0 Participants	0 Participants

Adverse Events

Bisphosphonate IV Q4W

Serious events: 19 serious events

Other events: 33 other events

Deaths: 0 deaths

Denosumab 180 mg Q12W

Serious events: 16 serious events

Other events: 29 other events

Deaths: 0 deaths

Denosumab 180 mg Q4W

Serious events: 21 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

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 multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Bisphosphonate IV Q4W n=35 participants at risk	Denosumab 180 mg Q12W n=35 participants at risk	Denosumab 180 mg Q4W n=38 participants at risk
Blood and lymphatic system disorders Anaemia	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 4/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Bone marrow failure	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Leukopenia	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Neutropenia	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Thrombocytopenia	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.9% 3/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Cardiopulmonary failure	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Pericardial effusion	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Sinus bradycardia	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Eye disorders Diplopia	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal distension	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Ascites	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Constipation	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Stomatitis	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Subileus	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Death	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders General physical health deterioration	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Obstruction	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pain	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Cholangitis acute	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Hepatic failure	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Hepatomegaly	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bronchopneumonia	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Catheter related infection	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Lung infection	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumonia	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumonia bacterial	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Staphylococcal sepsis	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection staphylococcal	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Femoral neck fracture	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Anorexia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Cachexia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Dehydration	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Other adverse events
Measure	Bisphosphonate IV Q4W n=35 participants at risk	Denosumab 180 mg Q12W n=35 participants at risk	Denosumab 180 mg Q4W n=38 participants at risk
Blood and lymphatic system disorders Anaemia	20.0% 7/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.4% 7/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Neutropenia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Thrombocytopenia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.9% 3/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Angina pectoris	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Sinus tachycardia	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Ear and labyrinth disorders Vertigo	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Eye disorders Conjunctivitis	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal pain	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Constipation	17.1% 6/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.0% 7/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.4% 7/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.2% 5/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastritis	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	20.0% 7/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	22.9% 8/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	23.7% 9/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Stomatitis	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.9% 3/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	17.1% 6/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Asthenia	20.0% 7/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	22.9% 8/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.4% 7/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chills	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.2% 5/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Mucosal inflammation	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Oedema peripheral	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	15.8% 6/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.2% 5/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bronchitis	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Influenza	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pharyngitis	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Upper respiratory tract infection	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.2% 5/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Weight decreased	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Anorexia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 4/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Decreased appetite	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.9% 3/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypocalcaemia	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 4/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 4/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.5% 4/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Bone pain	25.7% 9/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	34.3% 12/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	21.1% 8/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Muscle spasms	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.9% 3/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Muscular weakness	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.9% 1/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.4% 4/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.6% 1/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Myalgia	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	8.6% 3/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.3% 5/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.3% 2/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	5.7% 2/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/35 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/38 • 25 weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.