Trial Outcomes & Findings for A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density (NCT NCT00515463)

NCT ID: NCT00515463

Last Updated: 2013-10-31

Results Overview

An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 311 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2013-10-31

Participant Flow

Patients who successfully completed Study 20050141 (NCT00330460) were eligible to participate in this study. First Subject Enrolled: 30-May-2007 Last Subject Enrolled: 10-Sep-2007

Participant milestones

Measure	Denosumab - Vial Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.
Overall Study STARTED	155	156
Overall Study Received Study Medication	154	156
Overall Study COMPLETED	141	142
Overall Study NOT COMPLETED	14	14

Reasons for withdrawal

Measure	Denosumab - Vial Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.
Overall Study Physician Decision	4	2
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	3	4
Overall Study Lost to Follow-up	6	5
Overall Study Other	0	1

Baseline Characteristics

A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density

Baseline characteristics by cohort

Measure	Denosumab - Vial n=155 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=156 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.	Total n=311 Participants Total of all reporting groups
Age Continuous	62.5 Years STANDARD_DEVIATION 8.5 • n=93 Participants	62.9 Years STANDARD_DEVIATION 8.9 • n=4 Participants	62.7 Years STANDARD_DEVIATION 8.7 • n=27 Participants
Sex: Female, Male Female	155 Participants n=93 Participants	156 Participants n=4 Participants	311 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized White or Caucasian	124 Participants n=93 Participants	131 Participants n=4 Participants	255 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=93 Participants	1 Participants n=4 Participants	5 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	24 Participants n=93 Participants	18 Participants n=4 Participants	42 Participants n=27 Participants
Race/Ethnicity, Customized Asian	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized Japanese	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Patients who received ≥ 1 dose of investigational product, have a baseline and ≥ 1 post-baseline antibody assessment and did not have binding anti-denosumab antibodies present at baseline, and with evaluable antibody results at 6 months.

An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab.

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=146 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 6	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Patients who received ≥ 1 dose of investigational product, have a baseline and ≥ 1 post-baseline antibody assessment and did not have binding anti-denosumab antibodies present at baseline, and with evaluable antibody results at 12 months.

An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab.

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 12	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12

Population: Patients testing positive for binding antibodies to denosumab.

Samples demonstrating reactivity for binding antibodies to denosumab were to be tested for neutralizing or inhibitory effects in a cell-based bioassay.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry sodium

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Sodium Change From Baseline at Month 1	-0.1 mmol/L Standard Deviation 2.0	0.1 mmol/L Standard Deviation 1.7

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry sodium

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Sodium Change From Baseline at Month 6	-1.2 mmol/L Standard Deviation 2.0	-0.9 mmol/L Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Sodium Change From Baseline at Month 12

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Sodium Change From Baseline at Month 12	-0.9 mmol/L Standard Deviation 2.1	-0.6 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry potassium

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Potassium Change From Baseline at Month 1	0.02 mmol/L Standard Deviation 0.37	0 mmol/L Standard Deviation 0.39

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry potassium

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Potassium Change From Baseline at Month 6	0.01 mmol/L Standard Deviation 0.43	-0.07 mmol/L Standard Deviation 0.40

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry potassium

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Potassium Change From Baseline at Month 12	0.07 mmol/L Standard Deviation 0.40	0.04 mmol/L Standard Deviation 0.40

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry chloride

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Chloride Change From Baseline at Month 1	-0.1 mmol/L Standard Deviation 2.1	0.2 mmol/L Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry chloride

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Chloride Change From Baseline at Month 6	-0.9 mmol/L Standard Deviation 2.3	-0.4 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry chloride

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Chloride Change From Baseline at Month 12	-0.2 mmol/L Standard Deviation 2.1	0 mmol/L Standard Deviation 2.5

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry bicarbonate

Outcome measures

Measure	Denosumab - Vial n=145 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Bicarbonate Change From Baseline at Month 1	-0.3 mmol/L Standard Deviation 2.9	0 mmol/L Standard Deviation 2.9

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry bicarbonate

Outcome measures

Measure	Denosumab - Vial n=141 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Bicarbonate Change From Baseline at Month 6	0.2 mmol/L Standard Deviation 2.7	0.1 mmol/L Standard Deviation 2.9

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry bicarbonate

Outcome measures

Measure	Denosumab - Vial n=138 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Bicarbonate Change From Baseline at Month 12	-0.6 mmol/L Standard Deviation 2.8	-0.1 mmol/L Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry magnesium

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Magnesium Change From Baseline at Month 1	0.001 mmol/L Standard Deviation 0.092	-0.010 mmol/L Standard Deviation 0.080

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry magnesium

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Magnesium Change From Baseline at Month 6	-0.053 mmol/L Standard Deviation 0.073	-0.064 mmol/L Standard Deviation 0.080

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry magnesium

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Magnesium Change From Baseline at Month 12	-0.053 mmol/L Standard Deviation 0.062	-0.055 mmol/L Standard Deviation 0.074

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry blood urea nitrogen

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Blood Urea Nitrogen Change From Baseline at Month 1	0.01 mmol/L Standard Deviation 1.30	-0.04 mmol/L Standard Deviation 1.38

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry blood urea nitrogen

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Blood Urea Nitrogen Change From Baseline at Month 6	0.09 mmol/L Standard Deviation 1.40	0.11 mmol/L Standard Deviation 1.49

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry blood urea nitrogen

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Blood Urea Nitrogen Change From Baseline at Month 12	0.27 mmol/L Standard Deviation 1.44	-0.02 mmol/L Standard Deviation 1.50

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry creatinine

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Creatinine Change From Baseline at Month 1	0.24 umol/L Standard Deviation 8.01	0.12 umol/L Standard Deviation 7.76

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry creatinine

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Creatinine Change From Baseline at Month 6	-0.19 umol/L Standard Deviation 8.52	-1.29 umol/L Standard Deviation 8.23

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry creatinine

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Creatinine Change From Baseline at Month 12	1.40 umol/L Standard Deviation 9.53	0.76 umol/L Standard Deviation 8.28

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry aspartate amino transferase

Outcome measures

Measure	Denosumab - Vial n=146 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Aspartate Amino Transferase Change From Baseline at Month 1	-1.6 U/L Standard Deviation 13.0	0.4 U/L Standard Deviation 4.7

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry aspartate amino transferase

Outcome measures

Measure	Denosumab - Vial n=141 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Aspartate Amino Transferase Change From Baseline at Month 6	-1.6 U/L Standard Deviation 13.9	0.9 U/L Standard Deviation 7.7

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry aspartate amino transferase

Outcome measures

Measure	Denosumab - Vial n=138 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Aspartate Amino Transferase Change From Baseline at Month 12	-1.9 U/L Standard Deviation 13.5	0.2 U/L Standard Deviation 3.9

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry alanine amino transferase

Outcome measures

Measure	Denosumab - Vial n=145 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Alanine Amino Transferase Change From Baseline at Month 1	-3.1 U/L Standard Deviation 25.7	0.5 U/L Standard Deviation 5.5

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry alanine amino transferase

Outcome measures

Measure	Denosumab - Vial n=141 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Alanine Amino Transferase Change From Baseline at Month 6	-1.4 U/L Standard Deviation 27.8	4.2 U/L Standard Deviation 15.2

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry alanine amino transferase

Outcome measures

Measure	Denosumab - Vial n=138 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Alanine Amino Transferase Change From Baseline at Month 12	-2.7 U/L Standard Deviation 28.8	1.5 U/L Standard Deviation 6.3

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry total bilirubin

Outcome measures

Measure	Denosumab - Vial n=146 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Bilirubin Change From Baseline at Month 1	-0.35 umol/L Standard Deviation 2.53	-0.02 umol/L Standard Deviation 2.47

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry total bilirubin

Outcome measures

Measure	Denosumab - Vial n=141 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Bilirubin Change From Baseline at Month 6	-0.30 umol/L Standard Deviation 2.54	-0.20 umol/L Standard Deviation 2.67

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry total bilirubin

Outcome measures

Measure	Denosumab - Vial n=138 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Bilirubin Change From Baseline at Month 12	0.16 umol/L Standard Deviation 2.68	0.64 umol/L Standard Deviation 2.74

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry albumin

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Albumin Change From Baseline at Month 1	-0.46 g/L Standard Deviation 1.68	-0.40 g/L Standard Deviation 2.05

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry albumin

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Albumin Change From Baseline at Month 6	-0.34 g/L Standard Deviation 1.92	-0.51 g/L Standard Deviation 2.19

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry albumin

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Albumin Change From Baseline at Month 12	-0.26 g/L Standard Deviation 1.82	0 g/L Standard Deviation 2.03

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry total protein

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Protein Change From Baseline at Month 1	-0.59 g/L Standard Deviation 2.67	-0.54 g/L Standard Deviation 3.45

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry total protein

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Protein Change From Baseline at Month 6	-0.58 g/L Standard Deviation 3.00	-0.80 g/L Standard Deviation 3.33

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry total protein

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Protein Change From Baseline at Month 12	-1.35 g/L Standard Deviation 2.84	-0.91 g/L Standard Deviation 3.28

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory chemistry glucose

Outcome measures

Measure	Denosumab - Vial n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=149 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Glucose Change From Baseline at Month 1	-0.08 mmol/L Standard Deviation 1.27	0.03 mmol/L Standard Deviation 0.69

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory chemistry glucose

Outcome measures

Measure	Denosumab - Vial n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=144 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Glucose Change From Baseline at Month 6	-0.08 mmol/L Standard Deviation 1.37	0.05 mmol/L Standard Deviation 0.80

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory chemistry glucose

Outcome measures

Measure	Denosumab - Vial n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Glucose Change From Baseline at Month 12	-0.06 mmol/L Standard Deviation 1.27	0.08 mmol/L Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology red blood cells

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Red Blood Cells Change From Baseline at Month 1	0 10^12/L Standard Deviation 0.21	0.02 10^12/L Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology red blood cells

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Red Blood Cells Change From Baseline at Month 6	0.04 10^12/L Standard Deviation 0.22	0.04 10^12/L Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology red blood cells

Outcome measures

Measure	Denosumab - Vial n=137 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Red Blood Cells Change From Baseline at Month 12	-0.01 10^12/L Standard Deviation 0.22	0.02 10^12/L Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology hemoglobin

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Hemoglobin Change From Baseline at Month 1	-0.97 g/L Standard Deviation 6.00	-0.42 g/L Standard Deviation 6.24

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology hemoglobin

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Hemoglobin Change From Baseline at Month 6	0.84 g/L Standard Deviation 5.83	0.96 g/L Standard Deviation 6.34

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology hemoglobin

Outcome measures

Measure	Denosumab - Vial n=137 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Hemoglobin Change From Baseline at Month 12	-1.74 g/L Standard Deviation 6.09	-0.22 g/L Standard Deviation 6.62

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology reticulocytes

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Reticulocytes Change From Baseline at Month 1	3.70 10^9/L Standard Deviation 17.68	1.69 10^9/L Standard Deviation 17.41

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology reticulocytes

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Reticulocytes Change From Baseline at Month 6	19.54 10^9/L Standard Deviation 19.22	15.21 10^9/L Standard Deviation 20.69

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology reticulocytes

Outcome measures

Measure	Denosumab - Vial n=137 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Reticulocytes Change From Baseline at Month 12	19.09 10^9/L Standard Deviation 19.82	15.08 10^9/L Standard Deviation 19.73

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology platelets

Outcome measures

Measure	Denosumab - Vial n=138 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Platelets Change From Baseline at Month 1	5.24 10^9/L Standard Deviation 33.20	2.48 10^9/L Standard Deviation 36.20

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology platelets

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Platelets Change From Baseline at Month 6	28.26 10^9/L Standard Deviation 32.16	21.49 10^9/L Standard Deviation 53.82

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology platelets

Outcome measures

Measure	Denosumab - Vial n=133 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=139 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Platelets Change From Baseline at Month 12	25.19 10^9/L Standard Deviation 42.07	15.60 10^9/L Standard Deviation 41.82

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology white blood cells

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
White Blood Cells Change From Baseline at Month 1	0.23 10^9/L Standard Deviation 1.07	0.01 10^9/L Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology white blood cells

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
White Blood Cells Change From Baseline at Month 6	0.22 10^9/L Standard Deviation 1.38	-0.08 10^9/L Standard Deviation 1.47

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology white blood cells

Outcome measures

Measure	Denosumab - Vial n=137 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
White Blood Cells Change From Baseline at Month 12	0.47 10^9/L Standard Deviation 1.38	0.24 10^9/L Standard Deviation 1.47

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology total neutrophils

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Neutrophils Change From Baseline at Month 1	0.11 10^9/L Standard Deviation 0.85	-0.03 10^9/L Standard Deviation 1.10

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology total neutrophils

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Neutrophils Change From Baseline at Month 6	0.21 10^9/L Standard Deviation 1.23	-0.02 10^9/L Standard Deviation 1.23

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology total neutrophils

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Total Neutrophils Change From Baseline at Month 12	0.38 10^9/L Standard Deviation 1.15	0.12 10^9/L Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology eosinophils

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Eosinophils Change From Baseline at Month 1	-0.002 10^9/L Standard Deviation 0.065	-0.010 10^9/L Standard Deviation 0.059

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology eosinophils

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Eosinophils Change From Baseline at Month 6	0.020 10^9/L Standard Deviation 0.075	0.013 10^9/L Standard Deviation 0.104

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology eosinophils

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Eosinophils Change From Baseline at Month 12	-0.008 10^9/L Standard Deviation 0.071	0.025 10^9/L Standard Deviation 0.436

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology basophils

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Basophils Change From Baseline at Month 1	0.001 10^9/L Standard Deviation 0.025	0 10^9/L Standard Deviation 0.022

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology basophils

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Basophils Change From Baseline at Month 6	0.012 10^9/L Standard Deviation 0.026	0.012 10^9/L Standard Deviation 0.028

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology basophils

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Basophils Change From Baseline at Month 12	0.003 10^9/L Standard Deviation 0.026	0.006 10^9/L Standard Deviation 0.024

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology lymphocytes

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Lymphocytes Change From Baseline at Month 1	0.12 10^9/L Standard Deviation 0.43	0.04 10^9/L Standard Deviation 0.40

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology lymphocytes

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Lymphocytes Change From Baseline at Month 6	0.01 10^9/L Standard Deviation 0.37	-0.06 10^9/L Standard Deviation 0.45

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology lymphocytes

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Lymphocytes Change From Baseline at Month 12	0.08 10^9/L Standard Deviation 0.41	0.06 10^9/L Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 1.

Laboratory hematology monocytes

Outcome measures

Measure	Denosumab - Vial n=143 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=147 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Monocytes Change From Baseline at Month 1	0 10^9/L Standard Deviation 0.12	0.01 10^9/L Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 6.

Laboratory hematology monocytes

Outcome measures

Measure	Denosumab - Vial n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=142 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Monocytes Change From Baseline at Month 6	-0.03 10^9/L Standard Deviation 0.14	-0.03 10^9/L Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received ≥ 1 dose of investigational product with non-missing baseline and non-missing month 12.

Laboratory hematology monocytes

Outcome measures

Measure	Denosumab - Vial n=136 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=140 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Monocytes Change From Baseline at Month 12	0.01 10^9/L Standard Deviation 0.13	0.03 10^9/L Standard Deviation 0.14

SECONDARY outcome

Timeframe: Day 1 to Month 12

Population: Patients who received ≥ 1 dose of investigational product.

Participants with laboratory toxicity grade 3 (severe) or 4 (life-threatening), based on the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.

Outcome measures

Measure	Denosumab - Vial n=154 Participants Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=156 Participants Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe (PFS) on Day 1 and at Month 6.
Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 Number of patients with CTCAE grade 3 or 4	2 Participants	2 Participants
Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 Sodium - Grade 3 below normal (< 130 - 120 mmol/L)	0 Participants	1 Participants
Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 Potassium - Grade 3 above normal (>6.0-7.0 mmol/L)	0 Participants	1 Participants
Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 Magnesium -Grade 3 above normal (>1.23-3.30mmol/L)	2 Participants	0 Participants

Adverse Events

Denosumab - Vial

Serious events: 7 serious events

Other events: 32 other events

Deaths: 0 deaths

Denosumab - Pre-filled Syringe

Serious events: 12 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Denosumab - Vial n=154 participants at risk Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=156 participants at risk Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.
Blood and lymphatic system disorders Anaemia	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Atrial fibrillation	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Cardiac failure congestive	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Ventricular tachycardia	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumonia	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.3% 2/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Breast cancer stage I	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months 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) Endometrial cancer	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months 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) Lipoma	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Lung neoplasm malignant	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Malignant pleural effusion	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Ovarian adenoma	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Pancreatic carcinoma	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months 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) Vaginal cancer	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Transient ischaemic attack	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Uterine prolapse	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.65% 1/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Aortic stenosis	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Temporal arteritis	0.00% 0/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.64% 1/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Other adverse events

Measure	Denosumab - Vial n=154 participants at risk Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.	Denosumab - Pre-filled Syringe n=156 participants at risk Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.
Infections and infestations Sinusitis	3.2% 5/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.1% 8/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Upper respiratory tract infection	3.2% 5/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.4% 10/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 11/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 13/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	5.8% 9/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.1% 11/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.9% 3/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.1% 8/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	3.9% 6/154 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.1% 8/156 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of 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