A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01825785
• Collaborator: (none)
• Enrollment: 48
• Arms: 2
• Actual Duration (Months): 12.6

Study Details

Study Description

Brief Summary

The primary objective of this study was to assess the safety, tolerability, and immunogenicity potential of romosozumab following multiple subcutaneous (SC) administrations in healthy men and postmenopausal women with low bone mass.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal; Osteopenia	Drug: Romosozumab; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women With Low Bone Mass
• Actual Study Start Date: Nov 14, 2007
• Actual Primary Completion Date: Dec 2, 2008
• Actual Study Completion Date: Dec 2, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W) for 3 months.	Drug: Placebo; Administered by subcutaneous injection
Experimental: Romosozumab Participants were randomized to receive romosozumab administered by subcutaneous injection at doses of 1 mg/kg Q2W, 2 mg/kg Q4W, 2 mg/kg Q2W, or 3 mg/kg Q4W for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [169 days]

   Serious adverse events were any events that were fatal, were life-threatening (placed the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, were congenital anomalies or birth defects, or were other significant medical hazards. Relatedness to investigational product was assessed by the investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?'

2. Number of Participants Who Developed Antibodies to Romosozumab [Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.]

   All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing. Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.

Secondary Outcome Measures

1. Time to Maximum Observed Concentration (Tmax) of Romosozumab [Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.]

   Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.

2. Maximum Observed Concentration (Cmax) of Romosozumab [Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.]

3. Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab [Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.]

   Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)

4. Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab [Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.]

5. Accumulation Ratio (AR) for Romosozumab [Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.]

   The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.

6. Percent Change From Baseline in Bone Mineral Density of the Total Spine [Baseline and days 29, 85, 127, and 169]

   Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.

7. Percent Change From Baseline in Bone Mineral Density at the Total Hip [Baseline and days 29, 85, 127, and 169]

   Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

8. Percent Change From Baseline in Bone Mineral Density at the Femoral Hip [Baseline and days 29, 85, 127, and 169]

   Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

9. Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius [Baseline and days 29, 85, 127, and 169]

   Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

10. Percent Change From Baseline in Bone Mineral Density at the Total Wrist [Baseline and days 29, 85, 127, and 169]

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

11. Percent Change From Baseline in Bone Mineral Density of the Whole Body [Baseline and days 29, 85, 127, and 169]

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

12. Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) [Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169]

13. Percent Change From Baseline in Osteocalcin [Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169]

14. Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) [Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169]

15. Percent Change From Baseline in Serum C-telopeptide (sCTX) [Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169]

16. Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) [Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169]

17. Percent Change From Baseline in Sclerostin [Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169]

18. Change From Baseline in Ionized Calcium [Baseline and day 169 (or earlier for participants who discontinued before day 169)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males and females between 45 to 80 years of age

• Postmenopausal females

• Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine [L1-L4] or total evaluable vertebrae [if fewer than L1-L4] or total hip)

• 25-hydroxyvitamin D ≥ 20 ng/mL

• Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)

Exclusion Criteria:

• Osteoporosis defined by bone mineral density (BMD) T-scores < -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip

• Diagnosed with any condition that would affect bone metabolism

• Previous exposure to AMG 785

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01825785
• Other Study ID Numbers: 20060221
• First Posted: Apr 8, 2013
• Last Update Posted: Jul 5, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Bone Diseases, Metabolic

Study Results

Participant Flow

Recruitment Details	This study was conducted at 4 centers in the United States (US) from 14 November 2007 to 2 December 2008.
Pre-assignment Detail	Participants were enrolled into 1 of 6 cohorts. In each of cohorts 1 to 4, healthy postmenopausal women were randomized in a 3:1 ratio to receive romosozumab or placebo; In each of cohorts 5 and 6, healthy men were randomized in a 3:1 ratio to receive romosozumab or placebo.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Period Title: Overall Study
STARTED	12	6	6	6	6	6	6
COMPLETED	12	6	6	6	4	5	6
NOT COMPLETED	0	0	0	0	2	1	0

Baseline Characteristics

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men	Total
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Total of all reporting groups
Overall Participants	12	6	6	6	6	6	6	48
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (5.6)	56.8 (7.8)	57.3 (6.6)	62.5 (8.0)	54.3 (7.8)	61.2 (9.0)	59.3 (12.7)	58.7 (8.0)
Age, Customized (Count of Participants)
18 to 64 years	11 91.7%	4 66.7%	5 83.3%	4 66.7%	5 83.3%	3 50%	4 66.7%	36 75%
65 to 74 years	1 8.3%	2 33.3%	1 16.7%	1 16.7%	1 16.7%	3 50%	1 16.7%	10 20.8%
≥ 75 years	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 16.7%	2 4.2%
Sex: Female, Male (Count of Participants)
Female	8 66.7%	6 100%	6 100%	6 100%	6 100%	0 0%	0 0%	32 66.7%
Male	4 33.3%	0 0%	0 0%	0 0%	0 0%	6 100%	6 100%	16 33.3%
Race/Ethnicity, Customized (Count of Participants)
White	8 66.7%	4 66.7%	5 83.3%	3 50%	3 50%	3 50%	3 50%	29 60.4%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	1 2.1%
Hispanic or Latino	3 25%	2 33.3%	1 16.7%	3 50%	3 50%	3 50%	2 33.3%	17 35.4%
American Indian or Alaska Native	1 8.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Serious adverse events were any events that were fatal, were life-threatening (placed the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, were congenital anomalies or birth defects, or were other significant medical hazards. Relatedness to investigational product was assessed by the investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?'
Time Frame	169 days

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Any adverse event	10 83.3%	6 100%	6 100%	6 100%	5 83.3%	5 83.3%	5 83.3%
Serious adverse events	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 16.7%
Treatment-related adverse events	6 50%	1 16.7%	1 16.7%	4 66.7%	3 50%	3 50%	2 33.3%
Treatment-related serious adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Discontinuation due to adverse events	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%
Death on study	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants Who Developed Antibodies to Romosozumab
Description	All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing. Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.
Time Frame	Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Binding antibodies	0 0%	2 33.3%	2 33.3%	2 33.3%	3 50%	1 16.7%	3 50%
Neutralizing antibodies	0 0%	1 16.7%	1 16.7%	0 0%	0 0%	0 0%	1 16.7%

3. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Romosozumab
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be adequately estimated.

Arm/Group Title	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	5	6	6	5	5	6
First dose	3.0	3.0	4.5	3.0	3.0	5.0
Last dose	3.0	3.0	3.5	5.0	3.0	3.0

4. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Romosozumab
Time Frame	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be adequately estimated.

Arm/Group Title	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	5	6	6	5	5	6
First dose	6.80 (1.86)	15.7 (4.6)	14.8 (6.0)	24.5 (6.8)	8.06 (1.57)	27.7 (4.2)
Last dose	14.2 (4.3)	16.7 (3.3)	27.8 (8.4)	29.5 (8.7)	13.4 (4.4)	37.1 (8.1)

5. Secondary Outcome

Title	Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab
Description	Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)
Time Frame	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be adequately estimated.

Arm/Group Title	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	5	6	6	5	5	6
First dose	65.5 (15.6)	202 (48)	152 (63)	340 (73)	71.3 (11.8)	434 (81)
Last dose	141 (41)	231 (58)	321 (97)	462 (97)	136 (42)	555 (181)

6. Secondary Outcome

Title	Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab
Time Frame	Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be adequately estimated.

Arm/Group Title	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	5	6	6	5	5	6
Mean (Standard Deviation) [days]	7.02 (3.52)	6.51 (1.37)	9.32 (1.88)	6.84 (1.79)	6.77 (1.92)	6.07 (1.50)

7. Secondary Outcome

Title	Accumulation Ratio (AR) for Romosozumab
Description	The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.
Time Frame	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be adequately estimated.

Arm/Group Title	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	5	6	6	4	5	6
Mean (Standard Deviation) [ratio]	2.15 (0.45)	1.17 (0.26)	2.35 (0.90)	1.35 (0.19)	1.90 (0.49)	1.26 (0.23)

8. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Total Spine
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	-0.046 (0.778)	2.161 (0.177)	0.541 (1.296)	-0.495 (0.930)	-0.257 (0.623)	2.662 (0.804)	-0.660 (1.240)
Day 85	-0.843 (0.829)	3.579 (1.942)	3.881 (1.437)	3.853 (0.543)	3.146 (2.027)	3.135 (1.085)	4.157 (0.714)
Day 127	0.177 (0.907)	4.313 (3.057)	7.219 (1.243)	6.350 (0.732)	5.566 (2.142)	4.462 (1.787)	5.599 (0.756)
Day 169	-0.559 (1.013)	4.769 (1.916)	4.835 (1.116)	5.250 (1.630)	4.980 (2.111)	5.187 (0.825)	6.560 (1.293)

9. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Total Hip
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	-0.552 (0.347)	0.528 (0.617)	-0.768 (0.334)	0.112 (0.940)	-0.318 (1.182)	1.244 (1.368)	-0.902 (0.408)
Day 85	-0.613 (0.529)	1.066 (0.938)	0.639 (0.608)	2.116 (0.477)	2.088 (0.550)	1.134 (0.797)	0.731 (0.621)
Day 127	-0.793 (0.623)	0.702 (1.180)	0.621 (0.940)	2.855 (0.778)	3.996 (1.109)	2.111 (0.486)	1.455 (0.669)
Day 169	-0.511 (0.380)	1.423 (1.047)	0.894 (1.013)	3.176 (1.105)	2.094 (0.751)	1.007 (0.422)	0.370 (0.629)

10. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Femoral Hip
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	-0.394 (0.573)	0.300 (0.813)	-2.172 (1.331)	-0.811 (1.596)	-0.473 (1.987)	0.471 (1.919)	-0.597 (0.839)
Day 85	-1.175 (1.042)	1.360 (1.031)	0.578 (1.285)	-0.123 (1.001)	0.270 (1.176)	1.301 (0.681)	1.956 (1.493)
Day 127	-2.301 (0.745)	1.284 (1.255)	-1.005 (2.609)	1.471 (1.228)	1.332 (2.488)	1.861 (1.208)	0.091 (1.110)
Day 169	-0.447 (0.673)	0.801 (1.208)	-0.672 (1.783)	0.510 (1.103)	2.197 (1.674)	1.665 (1.582)	0.116 (2.003)

11. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	1.676 (0.897)	-0.220 (0.998)	-0.900 (0.733)	-2.052 (1.295)	-2.968 (0.930)	-0.435 (1.078)	-1.185 (1.101)
Day 85	0.609 (0.943)	-0.082 (1.012)	-2.740 (0.770)	0.803 (1.411)	-4.125 (0.421)	-2.504 (1.777)	-0.993 (1.478)
Day 127	0.835 (0.988)	0.680 (1.345)	-1.037 (0.668)	0.633 (1.450)	-4.739 (0.642)	-1.756 (1.158)	-2.263 (1.227)
Day 169	-0.191 (0.753)	0.522 (1.835)	0.240 (1.068)	-0.028 (1.943)	-3.647 (0.924)	-1.836 (1.145)	-1.449 (1.106)

12. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	0.135 (0.529)	-0.552 (1.134)	-0.014 (0.591)	-0.020 (0.944)	-0.438 (1.054)	0.757 (0.698)	0.021 (0.479)
Day 85	0.329 (0.604)	-0.063 (1.269)	-0.754 (0.533)	0.448 (0.549)	-3.621 (1.424)	-0.306 (0.510)	0.160 (0.296)
Day 127	0.236 (0.563)	-1.134 (1.388)	0.493 (0.792)	-0.739 (0.595)	-3.326 (1.895)	-0.914 (0.338)	-1.019 (0.647)
Day 169	0.417 (0.768)	-1.102 (1.834)	-0.928 (0.717)	-0.234 (1.126)	-2.632 (1.466)	-0.378 (0.818)	-0.211 (0.619)

13. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Whole Body
Description	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.
Time Frame	Baseline and days 29, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 29	-0.391 (0.347)	0.493 (0.580)	-1.122 (0.885)	-0.532 (0.188)	0.521 (0.567)	-0.058 (0.387)	-0.611 (0.344)
Day 85	0.103 (0.391)	0.259 (0.642)	-0.324 (0.827)	1.359 (0.276)	-0.151 (0.614)	0.459 (0.271)	0.243 (0.447)
Day 127	0.000 (0.371)	-1.068 (0.357)	-0.486 (0.938)	1.442 (0.862)	0.513 (0.600)	1.919 (0.839)	0.012 (0.562)
Day 169	-0.352 (0.320)	0.180 (1.143)	-0.294 (0.597)	1.284 (0.637)	0.801 (0.523)	1.285 (0.264)	0.218 (0.819)

14. Secondary Outcome

Title	Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)
Time Frame	Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point; data were not collected on days 50, 72, 74, and 76 for Q4W cohorts or on days 58, 60, or 62 for Q2W cohorts.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 2	-4.55 (3.83)	5.90 (4.97)	4.37 (3.98)	1.18 (4.35)	-0.71 (3.94)	8.46 (6.50)	-0.64 (13.43)
Day 4	0.81 (3.92)	14.72 (5.61)	16.32 (6.77)	7.99 (10.60)	9.53 (9.47)	15.32 (7.40)	10.72 (15.27)
Day 6	-5.99 (4.33)	46.69 (7.59)	32.85 (7.41)	23.19 (10.40)	32.18 (4.75)	27.78 (7.72)	33.83 (19.09)
Day 8	-1.65 (5.47)	45.25 (8.02)	37.14 (11.60)	42.17 (3.90)	69.31 (5.50)	47.44 (12.82)	70.63 (24.65)
Day 15	-0.87 (6.06)	58.03 (11.52)	66.12 (14.63)	76.66 (21.28)	103.66 (7.37)	58.81 (12.45)	123.92 (39.13)
Day 22	0.20 (5.41)	82.97 (21.49)	53.76 (19.99)	107.88 (19.52)	117.63 (9.76)	96.08 (13.47)	142.64 (34.70)
Day 29	-0.36 (5.54)	81.45 (20.35)	26.35 (10.41)	118.17 (17.03)	74.50 (16.33)	88.21 (11.96)	115.09 (26.83)
Day 36	5.42 (5.56)	78.03 (21.98)	59.50 (21.56)	140.47 (17.70)	103.87 (22.54)	105.96 (14.87)	147.40 (32.52)
Day 43	2.97 (5.73)	69.94 (20.47)	62.16 (23.95)	93.15 (20.34)	129.43 (21.06)	98.49 (17.18)	139.62 (31.52)
Day 50	-12.20 (5.65)	73.72 (23.57)	128.64 (16.55)	86.45 (14.88)
Day 57	1.74 (5.20)	51.66 (20.71)	3.28 (10.72)	95.15 (21.45)	77.00 (20.31)	76.98 (12.12)	74.16 (19.64)
Day 58	12.47 (6.76)	-7.77 (9.58)	54.04 (16.51)	82.95 (20.45)
Day 60	3.74 (5.80)	0.47 (5.66)	61.32 (17.08)	85.82 (19.44)
Day 62	5.62 (2.62)	11.85 (9.79)	64.38 (8.62)	94.88 (12.29)
Day 64	12.70 (12.29)	49.88 (14.11)	10.92 (11.34)	65.34 (19.45)	89.15 (12.34)	68.67 (11.96)	113.79 (18.18)
Day 71	0.11 (2.87)	51.25 (15.27)	20.01 (13.17)	88.47 (15.08)	64.99 (21.83)	60.58 (14.65)	113.62 (19.09)
Day 72	-2.97 (4.13)	32.99 (14.43)	71.55 (7.88)	63.76 (15.42)
Day 74	-11.52 (6.52)	49.16 (15.59)	89.11 (15.49)	71.99 (11.10)
Day 76	-5.50 (6.48)	45.95 (18.18)	100.22 (18.29)	78.57 (13.74)
Day 78	2.61 (5.24)	51.59 (18.64)	1.29 (11.31)	77.58 (19.98)	49.94 (17.55)	75.17 (23.08)	65.32 (13.57)
Day 85	-2.40 (3.78)	35.64 (11.54)	-3.90 (10.10)	79.77 (20.53)	24.94 (9.30)	54.06 (11.05)	44.44 (22.42)
Day 99	-1.01 (4.04)	3.21 (8.94)	-16.47 (8.68)	31.38 (18.42)	-5.07 (13.01)	14.97 (8.53)	12.17 (16.53)
Day 113	3.39 (5.36)	5.15 (8.34)	-14.06 (8.68)	-4.43 (9.13)	-9.38 (12.06)	-0.83 (9.20)	-7.13 (11.60)
Day 127	5.21 (6.81)	-3.26 (6.94)	-8.76 (9.73)	-9.51 (10.10)	-0.76 (17.80)	-7.63 (7.01)	-5.88 (9.47)
Day 141	4.35 (4.72)	-5.75 (5.62)	-19.84 (7.87)	2.88 (10.84)	22.42 (16.17)	-12.85 (12.79)	-9.24 (8.87)
Day 155	5.71 (4.91)	-5.45 (6.57)	-19.92 (9.17)	-0.73 (8.70)	5.49 (22.07)	1.76 (10.00)	-6.88 (9.24)
Day 169	7.58 (7.52)	4.79 (7.31)	-16.91 (7.34)	1.42 (6.81)	11.67 (11.51)	5.78 (9.42)	-7.07 (10.52)

15. Secondary Outcome

Title	Percent Change From Baseline in Osteocalcin
Time Frame	Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point; data were not collected on days 50, 72, 74, and 76 for Q4W cohorts or on days 58, 60, or 62 for Q2W cohorts.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 2	-0.19 (2.81)	6.61 (2.18)	-7.02 (4.56)	4.95 (4.34)	-4.09 (6.71)	9.53 (3.94)	-4.69 (5.12)
Day 4	-3.07 (2.54)	1.17 (6.38)	-13.51 (1.88)	-21.97 (5.50)	6.66 (6.63)	9.13 (17.95)	-9.27 (2.61)
Day 6	-4.74 (2.91)	-5.55 (6.37)	-14.09 (5.65)	-0.71 (6.79)	11.34 (6.43)	16.14 (13.24)	-2.00 (3.09)
Day 8	-3.68 (3.16)	-7.13 (3.83)	-4.14 (6.29)	22.82 (5.24)	41.85 (29.46)	17.92 (8.35)	-2.77 (4.06)
Day 15	-0.15 (2.34)	23.55 (10.75)	21.18 (6.94)	33.18 (9.05)	70.19 (15.1)	45.22 (13.53)	24.73 (5.35)
Day 22	-4.19 (2.06)	29.99 (8.26)	34.90 (16.55)	57.55 (11.24)	84.14 (12.09)	61.18 (19.45)	64.18 (10.17)
Day 29	0.02 (2.67)	49.44 (16.03)	39.52 (11.33)	81.71 (19.20)	90.08 (7.79)	55.58 (10.40)	79.45 (17.12)
Day 36	3.54 (2.61)	48.91 (10.93)	35.29 (9.36)	76.70 (12.51)	87.21 (16.45)	35.55 (12.53)	68.03 (8.81)
Day 43	1.20 (2.85)	45.46 (12.44)	30.75 (14.39)	77.15 (14.86)	90.14 (17.06)	57.62 (13.39)	82.02 (14.92)
Day 50	0.92 (5.00)	48.63 (13.20)	89.23 (18.31)	52.53 (19.49)
Day 57	4.07 (2.05)	49.28 (10.45)	-0.80 (15.19)	70.82 (16.48)	74.73 (8.81)	69.16 (19.15)	81.16 (16.26)
Day 58	7.56 (5.24)	8.12 (11.58)	75.01 (14.15)	75.70 (20.03)
Day 60	0.77 (5.59)	3.28 (11.15)	61.68 (9.37)	57.90 (19.58)
Day 62	14.12 (3.88)	2.04 (9.84)	67.70 (12.26)	47.72 (17.80)
Day 64	6.99 (4.49)	27.01 (9.96)	0.57 (10.33)	60.91 (11.91)	70.63 (10.99)	50.40 (22.63)	68.64 (16.90)
Day 71	1.87 (3.02)	39.49 (12.97)	27.96 (11.89)	81.01 (20.69)	77.51 (7.93)	51.69 (16.41)	79.70 (19.98)
Day 72	5.04 (5.29)	32.17 (9.97)	95.28 (20.14)	63.00 (13.12)
Day 74	-5.91 (2.36)	31.72 (10.55)	60.58 (13.97)	52.83 (12.14)
Day 76	-4.13 (7.92)	36.41 (9.63)	49.94 (3.93)	60.11 (16.94)
Day 78	-3.86 (3.35)	29.10 (8.42)	12.60 (11.10)	74.99 (13.37)	85.53 (15.09)	56.10 (19.30)	89.23 (23.86)
Day 85	-4.37 (3.11)	41.36 (11.92)	19.11 (9.44)	63.71 (11.99)	77.23 (16.82)	48.66 (12.49)	81.93 (31.34)
Day 99	-4.97 (3.94)	21.81 (7.95)	-9.45 (6.47)	49.49 (16.14)	31.98 (6.31)	33.70 (18.41)	30.28 (26.45)
Day 113	2.57 (4.85)	4.81 (8.41)	-11.70 (6.94)	31.46 (10.14)	20.24 (15.41)	12.25 (12.11)	6.17 (10.83)
Day 127	-0.34 (4.46)	2.79 (13.64)	-13.58 (4.48)	24.45 (15.36)	152.92 (144.30)	5.06 (14.88)	-3.88 (11.30)
Day 141	-3.80 (3.25)	-2.99 (8.22)	-25.33 (10.05)	21.63 (8.86)	17.25 (9.58)	8.58 (9.20)	-4.33 (7.28)
Day 155	-3.51 (4.78)	-6.23 (7.52)	-21.04 (7.35)	7.69 (8.01)	6.85 (14.51)	-7.10 (10.56)	-11.15 (14.79)
Day 169	1.25 (5.30)	-7.12 (7.84)	-20.27 (8.66)	16.81 (12.43)	24.60 (12.75)	2.19 (10.84)	-13.66 (10.56)

16. Secondary Outcome

Title	Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
Time Frame	Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point; data were not collected on days 50, 72, 74, and 76 for Q4W cohorts or on days 58, 60, or 62 for Q2W cohorts.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 2	-0.07 (2.80)	-4.51 (3.09)	-8.52 (3.73)	10.25 (3.50)	2.22 (4.04)	5.82 (2.73)	-0.80 (4.20)
Day 4	2.16 (3.11)	-2.74 (4.96)	-4.52 (7.52)	13.74 (3.39)	1.15 (6.14)	8.29 (6.28)	6.68 (3.66)
Day 6	2.26 (3.85)	11.82 (7.95)	7.76 (3.93)	14.17 (2.52)	12.59 (4.56)	3.64 (6.40)	6.93 (1.29)
Day 8	-3.30 (5.72)	20.02 (10.24)	9.69 (4.75)	21.51 (6.34)	21.87 (9.57)	24.20 (14.92)	20.98 (2.05)
Day 15	-3.26 (3.45)	31.67 (14.36)	31.96 (6.28)	33.68 (8.61)	51.97 (5.28)	15.58 (4.69)	46.38 (8.63)
Day 22	1.23 (3.14)	39.83 (11.04)	37.30 (4.15)	58.45 (14.40)	57.66 (9.91)	27.74 (7.34)	61.39 (14.64)
Day 29	-2.04 (2.94)	56.09 (19.29)	36.50 (8.85)	65.10 (14.72)	61.66 (13.21)	36.74 (10.53)	35.63 (13.78)
Day 36	0.04 (3.62)	54.87 (14.40)	28.89 (7.65)	72.39 (12.18)	63.55 (10.27)	43.48 (7.98)	34.27 (7.92)
Day 43	-1.93 (5.02)	49.26 (14.03)	39.33 (10.46)	68.54 (12.84)	66.74 (10.38)	27.55 (8.68)	52.27 (13.48)
Day 50	-5.81 (4.23)	45.38 (15.81)	68.67 (11.00)	34.97 (10.37)
Day 57	-2.15 (5.99)	41.39 (11.28)	38.07 (11.16)	65.28 (9.34)	47.38 (6.06)	38.47 (12.18)	44.53 (11.57)
Day 58	-2.79 (8.79)	29.12 (12.18)	39.33 (5.29)	44.24 (13.63)
Day 60	-7.26 (5.69)	18.64 (9.41)	38.07 (7.47)	36.75 (11.16)
Day 62	-8.41 (5.03)	24.58 (10.61)	38.52 (7.59)	31.71 (10.53)
Day 64	-8.42 (5.15)	34.60 (12.41)	19.54 (5.71)	77.50 (10.29)	38.38 (7.43)	27.78 (13.26)	45.24 (9.78)
Day 71	-8.14 (4.26)	34.29 (11.32)	16.29 (6.39)	52.77 (7.72)	44.72 (9.30)	25.46 (15.12)	47.47 (9.99)
Day 72	-7.83 (3.96)	32.18 (12.27)	50.19 (10.57)	19.60 (10.46)
Day 74	-11.97 (7.31)	20.46 (15.03)	57.85 (10.91)	15.07 (13.92)
Day 76	-9.30 (5.16)	40.67 (12.44)	51.82 (9.53)	17.91 (12.86)
Day 78	-3.54 (4.26)	33.07 (12.20)	19.74 (6.38)	64.46 (11.16)	43.30 (14.16)	13.37 (7.30)	47.07 (12.38)
Day 85	-1.70 (3.61)	26.01 (12.18)	7.70 (5.59)	69.90 (21.35)	38.27 (4.20)	18.68 (9.63)	42.53 (14.53)
Day 99	-3.35 (4.67)	23.36 (10.68)	-1.91 (3.22)	24.89 (14.52)	5.10 (1.62)	17.55 (17.51)	13.75 (6.54)
Day 113	7.31 (6.57)	10.26 (9.51)	-3.15 (3.85)	14.75 (5.08)	-5.26 (10.20)	-6.58 (3.92)	14.50 (5.38)
Day 127	0.52 (5.26)	-2.73 (7.12)	-2.30 (4.12)	9.62 (6.27)	1.13 (6.36)	-6.54 (7.54)	5.26 (5.75)
Day 141	2.55 (5.44)	-1.68 (6.67)	-5.98 (5.03)	2.90 (7.10)	3.75 (3.96)	-4.71 (4.43)	9.34 (3.25)
Day 155	5.25 (5.28)	-0.82 (6.82)	-4.10 (4.67)	6.15 (4.92)	5.12 (6.77)	-4.11 (3.38)	6.78 (8.32)
Day 169	3.90 (5.22)	-1.37 (6.27)	-5.72 (5.75)	2.33 (4.19)	16.26 (7.56)	-4.76 (5.36)	-0.42 (6.39)

17. Secondary Outcome

Title	Percent Change From Baseline in Serum C-telopeptide (sCTX)
Time Frame	Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point; data were not collected on days 50, 72, 74, and 76 for Q4W cohorts or on days 58, 60, or 62 for Q2W cohorts.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 2	-7.31 (4.30)	12.29 (9.15)	-11.32 (4.22)	8.05 (9.96)	-7.07 (7.36)	-10.15 (10.74)	-6.57 (3.50)
Day 4	-5.51 (5.87)	1.10 (12.49)	-19.03 (9.12)	-26.84 (4.63)	-25.85 (7.05)	-22.01 (3.66)	-34.13 (3.28)
Day 6	-12.60 (5.74)	-8.29 (12.56)	-26.11 (10.32)	-28.04 (7.70)	-36.98 (5.38)	-28.83 (6.44)	-35.78 (3.37)
Day 8	-17.79 (5.06)	-14.65 (11.02)	-31.59 (10.22)	-28.92 (3.05)	-35.93 (3.90)	-42.09 (4.09)	-43.93 (3.44)
Day 15	-18.86 (5.92)	-14.39 (9.41)	-35.11 (8.69)	-35.27 (4.30)	-33.00 (7.65)	-39.34 (2.85)	-48.74 (5.56)
Day 22	-12.98 (6.18)	-4.88 (9.99)	-29.97 (12.42)	-37.34 (3.50)	-22.85 (7.88)	-36.63 (6.67)	-39.21 (4.70)
Day 29	-10.94 (6.87)	0.31 (6.08)	-21.11 (8.86)	-25.43 (6.08)	-21.54 (10.95)	-32.76 (4.85)	-34.53 (8.14)
Day 36	-20.96 (7.87)	4.50 (11.96)	-21.42 (12.02)	-38.33 (2.21)	-29.20 (15.71)	-36.51 (9.31)	-50.32 (4.78)
Day 43	-14.14 (7.40)	3.91 (9.40)	-13.79 (15.06)	-34.04 (3.35)	-20.49 (12.73)	-28.54 (6.07)	-44.64 (7.31)
Day 50	-12.62 (7.98)	-4.78 (11.11)	-26.11 (5.90)	-22.42 (15.96)
Day 57	-17.59 (6.11)	14.35 (10.32)	-4.53 (17.99)	-23.74 (6.45)	-13.47 (15.73)	-25.25 (12.27)	-31.52 (7.89)
Day 58	-20.27 (7.58)	-9.15 (9.82)	-9.63 (15.05)	-28.19 (8.64)
Day 60	-14.95 (10.06)	-8.80 (13.64)	-22.34 (16.06)	-28.04 (11.68)
Day 62	-14.01 (10.87)	-25.09 (10.87)	-21.83 (18.62)	-41.37 (8.69)
Day 64	-10.22 (7.59)	6.59 (16.03)	-20.16 (8.81)	-20.09 (4.55)	-18.72 (14.04)	-20.03 (12.81)	-34.86 (10.25)
Day 71	-15.23 (5.58)	26.63 (14.92)	-14.42 (11.82)	-18.24 (7.26)	-14.03 (13.60)	-11.02 (18.12)	-38.38 (4.37)
Day 72	-19.21 (6.72)	11.70 (13.66)	-17.32 (7.84)	-8.98 (16.64)
Day 74	-6.15 (8.32)	7.40 (11.86)	-16.32 (6.94)	-9.80 (14.64)
Day 76	-19.35 (5.70)	11.70 (9.88)	-17.14 (9.24)	-17.12 (13.70)
Day 78	-18.50 (6.03)	9.18 (11.45)	-14.82 (10.85)	-17.99 (10.44)	11.88 (21.63)	-5.24 (18.22)	-21.66 (11.50)
Day 85	-12.69 (5.84)	14.95 (13.45)	8.97 (10.90)	-13.06 (9.08)	13.77 (22.18)	-16.89 (16.84)	-17.17 (10.09)
Day 99	-20.31 (5.21)	7.45 (8.41)	-15.79 (9.03)	-7.79 (8.64)	-5.14 (17.67)	-13.22 (17.06)	-8.18 (10.80)
Day 113	-15.61 (6.74)	4.66 (11.35)	-18.77 (12.28)	0.18 (13.58)	-7.88 (13.06)	-10.06 (10.22)	-8.20 (12.19)
Day 127	-19.03 (5.79)	-5.63 (13.21)	-12.96 (12.78)	0.46 (10.01)	-4.92 (18.73)	1.68 (14.91)	-16.92 (13.00)
Day 141	-21.10 (6.53)	4.86 (10.74)	-12.11 (14.71)	1.99 (9.89)	13.34 (14.80)	-22.48 (5.32)	-21.35 (9.69)
Day 155	-21.03 (5.72)	-0.02 (8.21)	-3.37 (12.01)	7.94 (6.33)	1.27 (14.71)	-14.43 (12.92)	-15.00 (14.96)
Day 169	-16.59 (6.74)	-1.13 (8.37)	-9.38 (12.56)	-0.92 (15.29)	-0.27 (10.41)	-15.61 (11.74)	-10.10 (9.54)

18. Secondary Outcome

Title	Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
Time Frame	Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point; data were not collected on days 50, 72, 74, and 76 for Q4W cohorts or on days 58, 60, or 62 for Q2W cohorts.

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 2	-5.72 (4.12)	-13.34 (6.82)	-2.09 (12.69)	7.94 (4.48)	-1.06 (5.09)	8.68 (5.69)	-5.04 (8.62)
Day 4	-18.14 (2.42)	0.35 (13.61)	18.59 (17.92)	2.94 (19.63)	1.34 (10.38)	-5.59 (31.57)	-3.14 (14.09)
Day 6	-22.64 (5.59)	-2.67 (8.79)	23.15 (15.52)	8.42 (17.70)	43.89 (18.45)	20.35 (21.69)	-4.22 (11.74)
Day 8	-22.84 (5.19)	-0.20 (6.59)	16.68 (13.79)	-7.82 (8.93)	12.58 (13.18)	-2.24 (9.43)	9.33 (24.92)
Day 15	-8.84 (5.93)	7.31 (12.26)	18.72 (12.98)	-10.00 (7.92)	67.27 (35.74)	-1.40 (14.42)	12.46 (27.05)
Day 22	-9.12 (4.45)	63.58 (41.80)	28.93 (15.69)	0.65 (17.49)	69.17 (22.48)	24.27 (21.16)	48.13 (37.16)
Day 29	-7.45 (6.70)	26.13 (14.71)	41.90 (10.87)	34.10 (25.51)	41.45 (17.60)	23.91 (21.12)	3.68 (19.02)
Day 36	-14.24 (4.63)	25.21 (11.90)	57.32 (15.99)	22.33 (25.29)	54.47 (18.24)	37.99 (26.79)	10.94 (14.70)
Day 43	-14.84 (5.36)	28.17 (11.49)	47.38 (19.72)	23.77 (26.38)	73.55 (22.75)	39.90 (17.90)	37.55 (31.09)
Day 50	-7.02 (9.81)	30.25 (19.47)	34.06 (31.75)	41.77 (27.38)
Day 57	-13.17 (6.57)	66.13 (35.48)	31.59 (25.03)	26.12 (20.92)	26.23 (13.73)	26.14 (26.62)	23.55 (28.82)
Day 58	-10.21 (7.73)	34.80 (16.82)	57.65 (25.32)	24.71 (15.33)
Day 60	-8.41 (9.17)	52.00 (20.18)	72.18 (16.59)	56.06 (31.40)
Day 62	-2.33 (10.30)	48.83 (20.01)	47.94 (18.36)	37.93 (22.34)
Day 64	-6.40 (8.29)	19.81 (11.29)	62.54 (17.33)	30.11 (13.35)	62.07 (18.54)	49.59 (26.25)	64.46 (31.92)
Day 71	-10.38 (3.86)	21.65 (17.69)	40.97 (15.06)	7.80 (17.50)	68.44 (26.27)	11.07 (24.13)	15.84 (12.81)
Day 72	-19.26 (8.34)	32.07 (19.22)	41.99 (35.57)	30.65 (17.43)
Day 74	-9.74 (6.73)	32.25 (25.26)	21.37 (17.25)	71.86 (39.62)
Day 76	-8.27 (6.56)	32.24 (14.18)	2.58 (14.33)	20.58 (20.98)
Day 78	-16.60 (5.70)	21.00 (14.55)	44.03 (11.32)	31.00 (22.68)	56.98 (25.29)	28.62 (13.12)	22.73 (27.28)
Day 85	-3.49 (5.98)	16.48 (11.90)	47.95 (9.94)	-3.99 (13.52)	24.90 (19.86)	33.55 (22.61)	29.25 (25.49)
Day 99	-20.78 (5.77)	20.49 (13.44)	14.08 (7.81)	5.91 (26.94)	12.34 (11.46)	3.12 (12.69)	2.69 (19.10)
Day 113	-7.05 (7.87)	0.16 (12.53)	13.91 (11.95)	-5.87 (11.21)	-10.83 (19.52)	13.19 (18.27)	16.73 (18.23)
Day 127	-12.50 (5.08)	-16.74 (7.08)	3.14 (14.76)	-11.32 (7.81)	-7.07 (6.79)	-2.02 (17.24)	6.96 (13.62)
Day 141	-16.41 (3.26)	-5.85 (9.79)	-8.33 (8.30)	-19.91 (6.71)	-4.19 (6.92)	-16.85 (13.53)	10.80 (18.12)
Day 155	-15.06 (4.78)	1.27 (8.24)	10.09 (11.69)	-15.78 (7.72)	17.62 (9.94)	-3.50 (10.45)	8.76 (16.71)
Day 169	-9.95 (7.25)	-18.84 (7.75)	-10.08 (13.08)	-19.71 (9.00)	30.72 (20.07)	-3.01 (10.49)	15.09 (21.69)

19. Secondary Outcome

Title	Percent Change From Baseline in Sclerostin
Time Frame	Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at baseline and each time point

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Day 15	-5.6 (4.7)	3135.6 (665.6)	5630.4 (478.9)	6087.5 (651.1)	7532.4 (627.8)	2809.3 (241.8)	6816.0 (775.1)
Day 29	-3.6 (5.4)	4068.2 (923.8)	2335.8 (283.2)	7713.1 (997.9)	4993.3 (890.2)	3904.4 (399.2)	4573.0 (614.4)
Day 43	4.4 (8.5)	4669.2 (1119.6)	6229.6 (475.2)	9023.8 (1003.7)	8471.0 (506.6)	4613.9 (486.2)	6486.0 (621.2)
Day 57	0.4 (7.2)	5143.9 (1145.2)	3024.9 (290.7)	8450.2 (545.0)	6137.5 (1319.7)	4450.8 (471.5)	4739.5 (660.2)
Day 71	-1.9 (5.7)	4949.6 (1133.1)	6905.1 (875.7)	10130.3 (1041.3)	9114.5 (812.4)	5405.1 (667.6)	7735.8 (949.8)
Day 85	-2.2 (5.8)	4886.5 (1085.4)	3004.2 (538.5)	10566.4 (1667.4)	5403.5 (1285.7)	5254.5 (588.9)	4873.7 (520.7)
Day 99	-3.5 (6.9)	2496.0 (806.8)	952.8 (362.7)	6748.3 (1165.3)	2124.2 (736.4)	1960.4 (461.1)	2183.7 (520.7)
Day 113	-7.3 (6.5)	883.2 (397.5)	399.4 (175.9)	3556.2 (627.9)	473.3 (129.2)	395.4 (57.0)	804.9 (257.7)
Day 127	0.2 (5.8)	364.9 (185.9)	161.5 (67.9)	1410.2 (273.0)	202.6 (58.2)	242.5 (150.0)	311.3 (117.9)
Day 141	2.1 (7.5)	203.9 (110.6)	84.6 (47.3)	524.3 (109.9)	178.2 (101.5)	74.2 (25.5)	128.2 (61.5)
Day 155	2.6 (9.0)	118.8 (78.9)	57.4 (35.5)	298.6 (67.4)	41.0 (21.8)	88.6 (43.3)	48.3 (36.6)
Day 169	1.9 (9.1)	76.1 (37.7)	40.3 (27.8)	177.3 (37.8)	845.3 (528.9)	713.7 (688.9)	16.8 (20.9)

20. Secondary Outcome

Title	Change From Baseline in Ionized Calcium
Time Frame	Baseline and day 169 (or earlier for participants who discontinued before day 169)

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	Placebo	Romosozumab 1 mg/kg Q2W in Women	Romosozumab 2 mg/kg Q4W in Women	Romosozumab 2 mg/kg Q2W in Women	Romosozumab 3 mg/kg Q4W in Women	Romosozumab 1 mg/kg Q2W in Men	Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.	Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
Measure Participants	12	6	6	6	6	6	6
Mean (Standard Deviation) [mg/dL]	0.05 (0.17)	0.12 (0.10)	0.06 (0.21)	-0.07 (0.18)	-0.05 (0.04)	-0.14 (0.18)	-0.06 (0.14)

Adverse Events

Time Frame	169 days
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Placebo		Romosozumab 1 mg/kg Q2W in Women		Romosozumab 2 mg/kg Q4W in Women		Romosozumab 2 mg/kg Q2W in Women		Romosozumab 3 mg/kg Q4W in Women		Romosozumab 1 mg/kg Q2W in Men		Romosozumab 3 mg/kg Q4W in Men
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W).		Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.		Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.		Participants were randomized to receive 2 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.		Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.		Participants were randomized to receive 1 mg/kg romosozumab by subcutaneous injection once every 2 weeks for 3 months.		Participants were randomized to receive 3 mg/kg romosozumab by subcutaneous injection once every 4 weeks for 3 months.
All Cause Mortality
	Placebo		Romosozumab 1 mg/kg Q2W in Women		Romosozumab 2 mg/kg Q4W in Women		Romosozumab 2 mg/kg Q2W in Women		Romosozumab 3 mg/kg Q4W in Women		Romosozumab 1 mg/kg Q2W in Men		Romosozumab 3 mg/kg Q4W in Men
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Romosozumab 1 mg/kg Q2W in Women		Romosozumab 2 mg/kg Q4W in Women		Romosozumab 2 mg/kg Q2W in Women		Romosozumab 3 mg/kg Q4W in Women		Romosozumab 1 mg/kg Q2W in Men		Romosozumab 3 mg/kg Q4W in Men
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Blood and lymphatic system disorders
HAEMORRHAGIC ANAEMIA	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Cardiac disorders
CORONARY ARTERY DISEASE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Gastrointestinal disorders
HAEMATOCHEZIA	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Romosozumab 1 mg/kg Q2W in Women		Romosozumab 2 mg/kg Q4W in Women		Romosozumab 2 mg/kg Q2W in Women		Romosozumab 3 mg/kg Q4W in Women		Romosozumab 1 mg/kg Q2W in Men		Romosozumab 3 mg/kg Q4W in Men
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		6/6 (100%)		6/6 (100%)		6/6 (100%)		5/6 (83.3%)		5/6 (83.3%)		5/6 (83.3%)
Blood and lymphatic system disorders
ANAEMIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
LYMPHADENOPATHY	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Cardiac disorders
CORONARY ARTERY DISEASE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
PALPITATIONS	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Ear and labyrinth disorders
EAR PAIN	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Eye disorders
CONJUNCTIVAL HYPERAEMIA	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
OCULAR HYPERAEMIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VISION BLURRED	3/12 (25%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/12 (8.3%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
ABDOMINAL PAIN UPPER	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
COLONIC POLYP	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
CONSTIPATION	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DENTAL CARIES	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DIARRHOEA	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
DIVERTICULUM INTESTINAL	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
DYSPEPSIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
FLATULENCE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
GINGIVAL ULCERATION	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HAEMORRHOIDAL HAEMORRHAGE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
LIP ULCERATION	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
NAUSEA	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
SWOLLEN TONGUE	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VOMITING	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
General disorders
ASTHENIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
AXILLARY PAIN	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
CHEST PAIN	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
FATIGUE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
FEELING COLD	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INFLUENZA LIKE ILLNESS	0/12 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE BRUISING	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE DISCOMFORT	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE ERYTHEMA	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE INDURATION	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE IRRITATION	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
INJECTION SITE PAIN	0/12 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
INJECTION SITE REACTION	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
OEDEMA PERIPHERAL	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SENSATION OF FOREIGN BODY	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VENIPUNCTURE SITE SWELLING	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Immune system disorders
HYPERSENSITIVITY	0/12 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SEASONAL ALLERGY	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Infections and infestations
BRONCHITIS	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
FUNGAL SKIN INFECTION	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
GASTROENTERITIS VIRAL	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INFECTED INSECT BITE	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
NASOPHARYNGITIS	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SINUSITIS	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
UPPER RESPIRATORY TRACT INFECTION	1/12 (8.3%)		3/6 (50%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)
URINARY TRACT INFECTION	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
VULVITIS	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
ARTHROPOD BITE	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
BACK INJURY	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CONTUSION	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
FOOT FRACTURE	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
LACERATION	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
LIGAMENT INJURY	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Investigations
BLOOD PRESSURE INCREASED	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
CARDIAC MURMUR	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
HEART RATE INCREASED	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
ANOREXIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HYPOCALCAEMIA	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)
BACK PAIN	2/12 (16.7%)		3/6 (50%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
BURSITIS	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
FIBROMYALGIA	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
JOINT EFFUSION	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
MUSCLE SPASMS	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
MUSCULAR WEAKNESS	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
MUSCULOSKELETAL CHEST PAIN	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
MUSCULOSKELETAL PAIN	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
MYALGIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PAIN IN EXTREMITY	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
SENSATION OF HEAVINESS	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SYNOVIAL CYST	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
TRIGGER FINGER	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SKIN PAPILLOMA	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
DIZZINESS	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DYSGEUSIA	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HEADACHE	4/12 (33.3%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		2/6 (33.3%)		3/6 (50%)		2/6 (33.3%)
LETHARGY	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
MULTIPLE SCLEROSIS	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
RESTLESS LEGS SYNDROME	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SOMNOLENCE	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Psychiatric disorders
ANXIETY	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DEPRESSION	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
INSOMNIA	1/12 (8.3%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Renal and urinary disorders
DYSURIA	0/12 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
POLLAKIURIA	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Reproductive system and breast disorders
VULVOVAGINAL BURNING SENSATION	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VULVOVAGINAL PRURITUS	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
DRY THROAT	1/12 (8.3%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
EPISTAXIS	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
NASAL CONGESTION	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
OROPHARYNGEAL PAIN	2/12 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
RHINITIS ALLERGIC	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
RHINORRHOEA	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
ACTINIC KERATOSIS	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PRURITUS	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
RASH PAPULAR	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Vascular disorders
HAEMATOMA	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HYPERTENSION	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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