A First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01059435
• Collaborator: (none)
• Enrollment: 74
• Arms: 2
• Actual Duration (Months): 6.7

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the safety and tolerability of romosozumab following single dose subcutaneous (SC) or intravenous (IV) administration in healthy men and postmenopausal women.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Ascending Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women
• Actual Study Start Date: Dec 13, 2006
• Actual Primary Completion Date: Jul 6, 2007
• Actual Study Completion Date: Jul 6, 2007

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.	Drug: Placebo; Administered subcutaneously or intravenously
Experimental: Romosozumab Participants were randomized to receive a single dose of romosozumab administered by subcutaneous or intravenous injection. The starting dose was 0.1 mg/kg, with sequential escalation up to 10 mg/kg.	Drug: Romosozumab; Administered subcutaneously or intravenously; Other Names: AMG 785 EVENITY™

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Adverse events were collected from the first dose of treatment up until day 29 for the 0.1 mg/kg and 0.3 mg/kg SC treatment groups, up to 57 days for the 1 mg/kg and 3 mg/kg IV/SC groups and for up to 85 days for the 5 mg/kg and 10 mg/kg SC/IV groups.]

   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 Anti-romosozumab Antibodies [Day 29 (all participants), day 57 (1, 3, 5, and 10 mg/kg treatment groups only) and at day 85 (5 and 10 mg/kg teatment groups only).]

   Binding anti-romosozumab antibody titers were assessed using a validated electrochemiluninescence (ECL) immunoassay. The limit of detection for this assay was 3.91 ng/mL of anti-romosozumab antibody in neat serum. Samples found to be positive for binding antibodies were further tested using a validated bioassay to determine if the antibodies were able to neutralize the activity of romosozumab. The limit of detection for this assay was ≥ 0.75 μg/mL.

Secondary Outcome Measures

1. Maximum Observed Concentration (Cmax) of Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

2. Time to Maximum Observed Concentration (Tmax) of Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

3. Initial Concentration Following IV Administration (C0) of Romosozumab [Day 1 at the end of infusion]

4. Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

5. Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

6. Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

   The plateau (beta, β) phase half-life (t½,β) was calculated from the natural log of 2 divided by the beta phase rate constant (λβ). λβ for a subject was estimated by linear regression of at least 3 contiguous time points that followed the Cmax and constituted a distinct phase that preceded the terminal phase.

7. Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

   The terminal (gamma, γ) phase half-life (t½,γ) was calculated from the natural log of 2 divided by the terminal rate constant (λz).

8. Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

   Defined as the maximum value postdose.

9. Time to Maximum Effect of P1NP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

   Defined as the time to maximum value postdose.

10. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

11. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab,]

12. Maximum Effect for Serum C-telopeptide (sCTX) [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the minimum value postdose.

13. Time to Maximum Effect of sCTX [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the time to minimum value postdose.

14. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

15. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

16. Maximum Effect for Osteocalcin [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the maximum value postdose.

17. Time to Maximum Effect of Osteocalcin [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the time to maximum value postdose.

18. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

19. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

20. Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the maximum value postdose.

21. Time to Maximum Effect of BSAP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the time to maximum value postdose.

22. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

23. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

24. Maximum Effect for Intact Parathyroid Hormone (iPTH) [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the maximum value postdose.

25. Time to Maximum Effect of iPTH [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

    Defined as the time to maximum value postdose.

26. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

27. Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH [Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.]

28. Percent Change From Baseline in Sclerostin [Baseline and days 15, 29, 43, 57, 71, and 85]

29. Serum Calcium Over Time [Dday 1 predose and at 4, 6, 8, 10, and 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85]

30. Ionized Calcium Over Time [Day 1 predose and at 4, 6, 8, 10, 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 59 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males or female between 45 to 59 years of age, inclusive

• Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy)

• Males must agree to use a condom during sexual intercourse with female partners who are of reproductive potential and to have their female partners use an additional effective means of contraception or to abstain from sexual intercourse for the duration of the study

• Has no history or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

Exclusion Criteria:

• Diagnosed with any condition that will affect bone metabolism

• Administration of the following medications within 6 months before study drug administration:

• Hormone replacement therapy [Infrequent use of estrogen vaginal creams (< 3 times per week) is allowed.]

• Calcitonin

• Parathyroid hormone (or any derivative)

• Supplemental Vitamin D > 1,000 IU/day

• Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)

• Anabolic steroids

• Calcitriol, and available analogues

• Administration of the following medications within 12 months before study drug administration:

• Bisphosphonates

• Fluoride for osteoporosis

• Administration of herbal medications within 2 weeks or 5 half-lives (whichever is longer) before study drug administration

• Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration

• Routine alcohol intake of > 2 drinks per day, on average, within 6 months of study drug administration

• Known sensitivity to mammalian-derived drug preparations

• Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome (AIDS)

• Any organic or psychiatric disorder which may pose a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results

• Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures

• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent

• Has a history of drug or alcohol abuse with the last 12 months and/or a positive urine test result at screening or admission

• Has any clinically significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation

• Has participated in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known

• Weight ≥ 98 kilograms (216 pounds) and/or height ≥ 78 inches

• Has donated or lost 400 milliliters or more of blood or plasma within 8 weeks of study drug administration

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

• Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011 Jan;26(1):19-26. doi: 10.1002/jbmr.173.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01059435
• Other Study ID Numbers: 20060220
• First Posted: Feb 1, 2010
• Last Update Posted: Jul 5, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Amgen: Amgen; First in Human; Postmenopausal; Phase 1
• Additional relevant MeSH terms: Bone Diseases, Metabolic

Study Results

Participant Flow

Recruitment Details	This was a single-center study conducted in the USA. The first participant enrolled on 13 December 2006 and the last participant completed the study on 06 July 2007.
Pre-assignment Detail	Participants were enrolled sequentially into 1 of 6 dose cohorts. Healthy postmenopausal women were randomized to romosozumab or placebo in a 3:1 ratio at 0.1, 0.3, 1 mg/kg SC, 1 mg/kg IV, 3, 5 mg/kg SC, 10 mg/kg SC, or 10 mg/kg IV; healthy men received romosozumab SC or IV, placebo SC or IV in a 3:3:1:1 ratio at doses of 1 mg/kg or 10 mg/kg.

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Period Title: Overall Study
STARTED	14	6	8	9	6	9	6	4	6	6
Received Study Drug	14	6	6	9	6	9	6	4	6	6
COMPLETED	14	6	6	9	6	9	6	4	6	6
NOT COMPLETED	0	0	2	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV	Total
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab	Total of all reporting groups
Overall Participants	14	6	6	9	6	9	6	4	6	6	72
Age (years) [Mean (Standard Deviation) ]
SC Dosing	52.79 (4.17)	53.00 (3.95)	53.33 (3.20)	52.00 (4.64)	55.00 (4.05)	51.89 (2.32)	52.50 (4.32)	NA (NA)	NA (NA)	NA (NA)	52.80 (3.79)
IV Dosing	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	52.50 (4.43)	49.33 (4.63)	51.00 (3.35)	50.75 (4.06)
Sex: Female, Male (Count of Participants)
Female	12 85.7%	6 100%	6 100%	6 66.7%	6 100%	6 66.7%	6 100%	2 50%	3 50%	3 50%	56 77.8%
Male	2 14.3%	0 0%	0 0%	3 33.3%	0 0%	3 33.3%	0 0%	2 50%	3 50%	3 50%	16 22.2%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	2 14.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	2 50%	1 16.7%	0 0%	6 8.3%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 1.4%
Hispanic or Latino	12 85.7%	6 100%	6 100%	9 100%	6 100%	9 100%	5 83.3%	2 50%	4 66.7%	6 100%	65 90.3%

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	Adverse events were collected from the first dose of treatment up until day 29 for the 0.1 mg/kg and 0.3 mg/kg SC treatment groups, up to 57 days for the 1 mg/kg and 3 mg/kg IV/SC groups and for up to 85 days for the 5 mg/kg and 10 mg/kg SC/IV groups.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Any adverse event	9 64.3%	4 66.7%	4 66.7%	1 11.1%	5 83.3%	6 66.7%	5 83.3%	2 50%	1 16.7%	2 33.3%
Serious adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%
Treatment-related adverse events	5 35.7%	4 66.7%	2 33.3%	0 0%	3 50%	4 44.4%	5 83.3%	0 0%	1 16.7%	1 16.7%
Serious treatment-related adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%
Discontinuations due to adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Deaths	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants Who Developed Anti-romosozumab Antibodies
Description	Binding anti-romosozumab antibody titers were assessed using a validated electrochemiluninescence (ECL) immunoassay. The limit of detection for this assay was 3.91 ng/mL of anti-romosozumab antibody in neat serum. Samples found to be positive for binding antibodies were further tested using a validated bioassay to determine if the antibodies were able to neutralize the activity of romosozumab. The limit of detection for this assay was ≥ 0.75 μg/mL.
Time Frame	Day 29 (all participants), day 57 (1, 3, 5, and 10 mg/kg treatment groups only) and at day 85 (5 and 10 mg/kg teatment groups only).

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Binding antibody positive	0 0%	0 0%	0 0%	0 0%	0 0%	2 22.2%	2 33.3%	0 0%	0 0%	2 33.3%
Neutralizing antibody positive	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Romosozumab
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received subcutaneous romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.
Measure Participants	6	6	9	6	9	6
Mean (Standard Deviation) [ng/mL]	375 (182)	1280 (653)	4890 (1780)	21300 (5170)	33500 (8290)	75200 (15900)

4. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Romosozumab
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received subcutaneous romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.
Measure Participants	6	6	9	6	9	6
Median (Full Range) [days]	1.5	2.5	3	5	5	4.5

5. Secondary Outcome

Title	Initial Concentration Following IV Administration (C0) of Romosozumab
Time Frame	Day 1 at the end of infusion

Outcome Measure Data

Analysis Population Description

All treated participants who received intravenously administered romosozumab

Arm/Group Title	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	6	6
Mean (Standard Deviation) [ng/mL]	24900 (4670)	132000 (13700)

6. Secondary Outcome

Title	Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	6	6	9	6	9	6	6	6
Mean (Standard Deviation) [µg*hr/mL]	78.5 (22.6)	288 (144)	1480 (605)	8170 (1810)	16900 (4350)	43400 (8550)	3020 (989)	24400 (4400)

7. Secondary Outcome

Title	Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	6	6	9	6	9	6	6	6
Mean (Standard Deviation) [mL/hr/kg]	1.39 (0.489)	1.35 (0.841)	0.873 (0.647)	0.383 (0.0901)	0.319 (0.0998)	0.236 (0.0370)	0.362 (0.117)	0.210 (0.0361)

8. Secondary Outcome

Title	Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab
Description	The plateau (beta, β) phase half-life (t½,β) was calculated from the natural log of 2 divided by the beta phase rate constant (λβ). λβ for a subject was estimated by linear regression of at least 3 contiguous time points that followed the Cmax and constituted a distinct phase that preceded the terminal phase.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received 3, 5, or 10 mg/kg romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	0	0	0	6	9	6	0	6
Mean (Standard Deviation) [days]	11.1 (3.70)	12.9 (3.14)	18.0 (3.54)	10.6 (1.70)

9. Secondary Outcome

Title	Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab
Description	The terminal (gamma, γ) phase half-life (t½,γ) was calculated from the natural log of 2 divided by the terminal rate constant (λz).
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants who received romosozumab

Arm/Group Title	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	6	6	9	6	9	6	6	6
Mean (Standard Deviation) [days]	5.20 (1.36)	5.13 (0.640)	5.50 (0.322)	6.68 (0.961)	5.81 (0.874)	5.88 (1.60)	4.49 (0.974)	4.93 (0.639)

10. Secondary Outcome

Title	Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)
Description	Defined as the maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [ng/mL]	69.8 (32.0)	57.7 (22.8)	60.9 (14.4)	60.7 (10.8)	100.8 (49.6)	125.1 (44.2)	141.4 (24.8)	77.0 (35.3)	76.3 (19.8)	173.4 (43.3)

11. Secondary Outcome

Title	Time to Maximum Effect of P1NP
Description	Defined as the time to maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Median (Full Range) [days]	39.5	11.0	4.5	15.0	22.0	22.0	25.5	43.0	15.0	18.5

12. Secondary Outcome

Title	Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/mL]	1529 (633)	1431 (548)	1564 (377)	1473 (304)	2300 (1099)	2780 (1007)	2986 (306)	1714 (782)	1794 (434)	3940 (944)

13. Secondary Outcome

Title	Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab,

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/mL]	3234 (1462)	1431 (548)	1564 (377)	2782 (513)	3962 (1702)	6759 (2434)	7846 (1264)	4487 (2352)	3138 (723)	8976 (2531)

14. Secondary Outcome

Title	Maximum Effect for Serum C-telopeptide (sCTX)
Description	Defined as the minimum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [ng/mL]	0.3 (0.2)	0.4 (0.2)	0.3 (0.1)	0.3 (0.1)	0.4 (0.1)	0.2 (0.1)	0.2 (0.1)	0.3 (0.2)	0.2 (0.1)	0.2 (0.1)

15. Secondary Outcome

Title	Time to Maximum Effect of sCTX
Description	Defined as the time to minimum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Median (Full Range) [days]	1.0	1.0	1.0	1.0	1.0	8.0	6.0	18.5	1.0	1.0

16. Secondary Outcome

Title	Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/mL]	20 (8)	21 (6)	18 (5)	15 (6)	14 (3)	11 (4)	8 (3)	21 (8)	13 (3)	12 (5)

17. Secondary Outcome

Title	Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/mL]	37 (18)	21 (6)	18 (5)	30 (13)	29 (7)	41 (18)	40 (15)	44 (20)	26 (6)	44 (13)

18. Secondary Outcome

Title	Maximum Effect for Osteocalcin
Description	Defined as the maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [µg/L]	28.9 (8.1)	25.6 (8.0)	25.8 (4.8)	26.6 (5.5)	36.9 (10.9)	39.0 (12.7)	53.9 (10.5)	35.9 (13.9)	28.8 (7.7)	53.5 (12.8)

19. Secondary Outcome

Title	Time to Maximum Effect of Osteocalcin
Description	Defined as the time to maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Median (Full Range) [days]	29.0	15.0	18.5	22.0	22.0	29.0	36.0	34.0	22.0	32.5

20. Secondary Outcome

Title	Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*µg/L]	617 (209)	611 (191)	658 (153)	570 (139)	753 (234)	757 (225)	881 (162)	759 (286)	559 (73)	973 (212)

21. Secondary Outcome

Title	Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*µg/L]	1259 (505)	611 (191)	658 (153)	1129 (256)	1487 (453)	2470 (827)	2964 (563)	1897 (519)	1132 (131)	2988 (460)

22. Secondary Outcome

Title	Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP)
Description	Defined as the maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [µg/L]	21.0 (5.7)	18.0 (6.7)	17.2 (3.2)	17.7 (4.7)	26.1 (7.8)	24.6 (8.6)	29.9 (8.2)	19.6 (3.7)	15.9 (4.5)	36.4 (15.9)

23. Secondary Outcome

Title	Time to Maximum Effect of BSAP
Description	Defined as the time to maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Median (Full Range) [days]	36.0	16.5	13.0	15.0	22.0	22.0	22.0	46.5	13.5	29.0

24. Secondary Outcome

Title	Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*µg/L]	462 (157)	460 (172)	460 (127)	422 (100)	588 (152)	540 (210)	639 (176)	448 (73)	376 (102)	780 (325)

25. Secondary Outcome

Title	Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*µg/L]	958 (428)	460 (172)	460 (127)	815 (190)	1120 (303)	1496 (527)	1860 (508)	1138 (191)	731 (177)	2033 (780)

26. Secondary Outcome

Title	Maximum Effect for Intact Parathyroid Hormone (iPTH)
Description	Defined as the maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [ng/L]	43.3 (12.6)	38.7 (11.9)	54.5 (13.1)	49.9 (20.5)	62.8 (10.9)	66.0 (20.0)	76.3 (15.7)	64.8 (27.8)	52.7 (20.1)	59.7 (14.9)

27. Secondary Outcome

Title	Time to Maximum Effect of iPTH
Description	Defined as the time to maximum value postdose.
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Median (Full Range) [days]	11.0	11.0	25.5	22.0	22.0	22.0	15.0	25.5	11.0	18.5

28. Secondary Outcome

Title	Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/L]	817 (295)	823 (202)	1234 (341)	1002 (405)	1270 (198)	1240 (342)	1422 (411)	1235 (488)	1074 (406)	1239 (267)

29. Secondary Outcome

Title	Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH
Time Frame	Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Mean (Standard Deviation) [days*ng/L]	1592 (689)	823 (202)	1234 (341)	1971 (850)	2523 (406)	3483 (1057)	4195 (1144)	3100 (1077)	2072 (749)	3515 (1127)

30. Secondary Outcome

Title	Percent Change From Baseline in Sclerostin
Time Frame	Baseline and days 15, 29, 43, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed on days 71 and 85.

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Day 15	53.2 (54.3)	465.5 (49.9)	835.1 (130.4)	2123.8 (377.6)	7965.9 (792.9)	12375.7 (1375.4)	17774.8 (2444.0)	6.7 (11.4)	3776.0 (461.5)	14230.0 (2428.1)
Day 29	-8.4 (7.0)	129.0 (33.3)	183.0 (19.6)	717.4 (92.4)	5140.2 (373.7)	9763.2 (1252.8)	18870.9 (2707.3)	-4.3 (8.7)	816.7 (222.3)	11715.5 (2177.0)
Day 43	-9.8 (14.1)	223.2 (18.1)	1988.3 (339.9)	4968.7 (714.7)	13902.7 (2381.9)	4.9 (8.7)	196.1 (48.7)	4576.0 (1086.7)
Day 57	-3.7 (8.6)	83.4 (14.5)	810.2 (169.9)	2004.9 (421.5)	6469.6 (1000.3)	15.6 (0.6)	49.9 (17.4)	1430.0 (538.0)
Day 71	86.9 (88.3)	610.4 (151.6)	2080.8 (689.0)	-5.5 (5.4)	426.9 (119.6)
Day 85	11.6 (16.6)	232.1 (49.0)	758.0 (270.1)	0.8 (13.4)	109.8 (30.6)

31. Secondary Outcome

Title	Serum Calcium Over Time
Time Frame	Dday 1 predose and at 4, 6, 8, 10, and 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed after day 57.

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Day 1 Pre-dose	9.49 (0.34)	9.45 (0.38)	9.50 (0.33)	9.48 (0.27)	9.42 (0.25)	9.53 (0.26)	9.38 (0.24)	9.60 (0.22)	9.23 (0.15)	9.37 (0.15)
Day 1 Hour 4	9.46 (0.30)	9.62 (0.19)	9.45 (0.26)	9.38 (0.16)	9.38 (0.15)	9.59 (0.27)	9.35 (0.40)	9.45 (0.21)	9.43 (0.22)	9.40 (0.17)
Day 1 Hour 6	9.49 (0.26)	9.38 (0.22)	9.50 (0.14)	9.47 (0.17)	9.60 (0.24)	9.48 (0.35)	9.25 (0.36)	9.18 (0.13)	9.38 (0.31)	9.40 (0.15)
Day 1 Hour 8	9.38 (0.22)	9.47 (0.29)	9.33 (0.23)	9.29 (0.18)	9.28 (0.12)	9.42 (0.28)	9.27 (0.33)	9.38 (0.21)	9.35 (0.10)	9.22 (0.12)
Day 1 Hour 10	9.53 (0.26)	9.62 (0.31)	9.50 (0.27)	9.40 (0.30)	9.38 (0.19)	9.36 (0.31)	9.28 (0.27)	9.50 (0.22)	9.45 (0.16)	9.42 (0.15)
Day 1 Hour 12	9.53 (0.28)	9.55 (0.27)	9.57 (0.31)	9.49 (0.31)	9.37 (0.34)	9.52 (0.26)	9.27 (0.34)	9.40 (0.24)	9.47 (0.19)	9.45 (0.19)
Day 2	9.46 (0.34)	9.55 (0.21)	9.23 (0.28)	9.39 (0.21)	9.37 (0.33)	9.46 (0.29)	9.23 (0.29)	8.55 (1.77)	9.05 (0.41)	9.28 (0.15)
Day 3	9.30 (0.61)	9.37 (0.29)	9.25 (0.39)	9.20 (0.34)	9.35 (0.14)	9.38 (0.41)	9.18 (0.17)	9.40 (0.24)	9.13 (0.51)	9.27 (0.18)
Day 4	9.49 (0.25)	9.38 (0.27)	9.37 (0.27)	9.18 (0.64)	9.27 (0.12)	9.40 (0.30)	9.13 (0.22)	9.23 (0.50)	8.88 (0.84)	9.18 (0.13)
Day 5	9.42 (0.36)	9.38 (0.21)	9.37 (0.25)	9.38 (0.24)	9.32 (0.25)	9.24 (0.26)	9.15 (0.18)	9.55 (0.17)	9.20 (0.15)	9.12 (0.19)
Day 6	9.56 (0.26)	9.45 (0.29)	9.45 (0.26)	9.51 (0.20)	9.35 (0.10)	9.36 (0.26)	9.18 (0.15)	9.35 (0.24)	9.32 (0.19)	9.23 (0.12)
Day 8	9.41 (0.31)	9.45 (0.20)	9.28 (0.23)	9.36 (0.44)	9.23 (0.10)	9.33 (0.40)	8.93 (0.28)	9.30 (0.22)	9.18 (0.29)	9.20 (0.37)
Day 11	9.32 (0.29)	9.38 (0.33)	9.07 (0.24)	9.39 (0.25)	9.30 (0.39)	9.19 (0.36)	8.70 (0.75)	9.30 (0.22)	9.13 (0.29)	9.18 (0.26)
Day 15	9.39 (0.26)	9.60 (0.17)	9.40 (0.32)	9.26 (0.21)	9.22 (0.19)	9.06 (0.35)	8.97 (0.18)	9.33 (0.22)	9.28 (0.33)	9.00 (0.36)
Day 22	9.35 (0.33)	9.53 (0.45)	9.18 (0.35)	9.33 (0.32)	9.22 (0.17)	9.14 (0.47)	8.90 (0.23)	9.48 (0.13)	9.18 (0.22)	9.08 (0.15)
Day 29	9.49 (0.32)	9.58 (0.22)	9.40 (0.26)	9.44 (0.37)	9.20 (0.27)	9.32 (0.28)	8.95 (0.19)	9.38 (0.13)	9.17 (0.21)	9.15 (0.23)
Day 36	9.40 (0.45)	9.33 (0.26)	9.23 (0.30)	9.00 (0.26)	9.07 (0.26)	9.25 (0.30)	9.18 (0.35)	9.00 (0.30)
Day 43	9.33 (0.39)	9.32 (0.21)	9.37 (0.31)	9.23 (0.36)	8.90 (0.26)	9.28 (0.33)	9.25 (0.25)	9.15 (0.33)
Day 50	9.35 (0.26)	9.30 (0.41)	9.03 (0.21)	9.40 (0.34)	8.98 (0.19)	9.33 (0.33)	9.43 (0.50)	9.07 (0.23)
Day 57	9.46 (0.30)	9.47 (0.36)	9.35 (0.29)	9.18 (0.49)	9.28 (0.17)	9.33 (0.29)	9.25 (0.27)	9.02 (0.21)
Day 64	9.22 (0.15)	9.28 (0.42)	8.90 (0.36)	9.25 (0.07)	9.18 (0.35)
Day 71	9.36 (0.18)	9.47 (0.47)	9.05 (0.36)	9.20 (0.14)	9.20 (0.14)
Day 78	9.30 (0.24)	9.31 (0.32)	9.07 (0.40)	9.20 (0.00)	9.12 (0.34)
Day 85	9.12 (0.08)	9.47 (0.35)	8.82 (0.31)	9.10 (0.28)	9.05 (0.26)

32. Secondary Outcome

Title	Ionized Calcium Over Time
Time Frame	Day 1 predose and at 4, 6, 8, 10, 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed after day 57.

Arm/Group Title	Placebo SC	Romosozumab 0.1 mg/kg SC	Romosozumab 0.3 mg/kg SC	Romosozumab 1.0 mg/kg SC	Romosozumab 3.0 mg/kg SC	Romosozumab 5.0 mg/kg SC	Romosozumab 10.0 mg/kg SC	Placebo IV	Romosozumab 1.0 mg/kg IV	Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.	Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.	Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.	Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.	Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.	Participants received a single intravenous (IV) injection of matching placebo.	Participants received a single intravenous injection of 1.0 mg/kg romosozumab.	Participants received a single intravenous injection of 5.0 mg/kg romosozumab
Measure Participants	14	6	6	9	6	9	6	4	6	6
Day 1 Pre-dose	5.02 (0.20)	4.95 (0.18)	5.02 (0.16)	5.01 (0.18)	4.88 (0.08)	5.07 (0.18)	4.85 (0.10)	5.30 (0.12)	5.18 (0.15)	5.27 (0.15)
Day 1 Hour 4	5.06 (0.20)	5.02 (0.17)	5.10 (0.13)	5.11 (0.24)	5.03 (0.10)	5.12 (0.32)	4.95 (0.08)	5.40 (0.14)	5.35 (0.18)	5.40 (0.09)
Day 1 Hour 6	4.97 (0.19)	4.93 (0.10)	4.98 (0.10)	4.97 (0.21)	4.93 (0.08)	5.06 (0.24)	4.87 (0.12)	5.10 (0.14)	5.28 (0.15)	5.30 (0.09)
Day 1 Hour 8	4.93 (0.14)	4.92 (0.15)	5.00 (0.11)	5.00 (0.21)	4.90 (0.06)	5.04 (0.27)	4.78 (0.12)	5.30 (0.08)	5.28 (0.17)	5.30 (0.09)
Day 1 Hour 10	5.06 (0.20)	5.00 (0.09)	5.05 (0.10)	5.11 (0.19)	4.95 (0.15)	5.07 (0.34)	4.88 (0.12)	5.30 (0.12)	5.32 (0.18)	5.38 (0.15)
Day 1 Hour 12	5.01 (0.18)	4.95 (0.08)	5.00 (0.15)	5.01 (0.20)	4.93 (0.16)	5.03 (0.30)	4.80 (0.11)	5.28 (0.22)	5.25 (0.10)	5.33 (0.08)
Day 2	5.04 (0.20)	5.03 (0.16)	4.92 (0.17)	5.03 (0.17)	4.98 (0.12)	5.04 (0.19)	4.88 (0.15)	5.28 (0.10)	5.08 (0.08)	5.18 (0.10)
Day 3	5.06 (0.19)	5.00 (0.13)	4.97 (0.14)	5.00 (0.14)	4.95 (0.08)	5.12 (0.20)	4.85 (0.05)	5.28 (0.13)	5.17 (0.12)	5.25 (0.14)
Day 4	5.05 (0.17)	4.97 (0.15)	4.85 (0.16)	5.03 (0.10)	4.87 (0.12)	5.11 (0.20)	4.82 (0.08)	5.23 (0.17)	5.20 (0.09)	5.17 (0.14)
Day 5	5.02 (0.18)	4.93 (0.10)	4.88 (0.25)	5.04 (0.12)	4.93 (0.12)	5.04 (0.19)	4.80 (0.06)	5.40 (0.14)	5.18 (0.12)	5.15 (0.14)
Day 6	5.02 (0.16)	4.91 (0.14)	4.97 (0.12)	5.06 (0.11)	4.88 (0.10)	5.02 (0.14)	4.80 (0.06)	5.23 (0.10)	5.23 (0.12)	5.05 (0.10)
Day 8	5.02 (0.17)	4.98 (0.08)	4.92 (0.10)	5.01 (0.24)	4.83 (0.10)	4.89 (0.18)	5.00 (0.14)	5.23 (0.17)	5.17 (0.12)	5.07 (0.19)
Day 11	5.01 (0.14)	5.05 (0.14)	4.93 (0.14)	5.06 (0.17)	4.90 (0.13)	4.92 (0.15)	5.00 (0.11)	5.23 (0.13)	5.20 (0.13)	5.10 (0.20)
Day 15	5.05 (0.16)	5.10 (0.19)	4.92 (0.12)	5.02 (0.16)	4.83 (0.12)	4.98 (0.19)	5.00 (0.06)	5.20 (0.22)	5.25 (0.12)	5.07 (0.12)
Day 22	5.03 (0.17)	5.05 (0.18)	4.82 (0.12)	4.92 (0.16)	4.85 (0.08)	5.08 (0.17)	5.05 (0.08)	5.18 (0.24)	5.12 (0.15)	5.05 (0.21)
Day 29	5.13 (0.17)	5.05 (0.08)	4.92 (0.17)	5.02 (0.20)	4.85 (0.08)	5.22 (0.12)	5.03 (0.16)	5.28 (0.17)	5.22 (0.10)	5.13 (0.20)
Day 36	5.16 (0.17)	4.96 (0.14)	5.07 (0.16)	5.11 (0.18)	4.96 (0.16)	5.28 (0.13)	5.18 (0.10)	5.18 (0.15)
Day 43	5.18 (0.23)	4.99 (0.15)	5.22 (0.13)	5.26 (0.21)	5.02 (0.08)	5.23 (0.17)	5.30 (0.13)	5.18 (0.12)
Day 50	5.21 (0.19)	5.19 (0.16)	5.20 (0.11)	5.16 (0.11)	5.00 (0.13)	5.28 (0.15)	5.32 (0.13)	5.15 (0.14)
Day 57	5.26 (0.14)	5.22 (0.14)	5.22 (0.10)	5.21 (0.15)	5.18 (0.13)	5.33 (0.17)	5.23 (0.08)	5.25 (0.15)
Day 64	5.18 (0.11)	5.22 (0.18)	5.13 (0.14)	5.15 (0.07)	5.17 (0.14)
Day 71	5.18 (0.08)	5.38 (0.16)	5.12 (0.18)	5.30 (0.28)	5.20 (0.13)
Day 78	5.28 (0.08)	5.30 (0.17)	5.15 (0.19)	5.15 (0.07)	5.27 (0.15)
Day 85	5.24 (0.11)	5.36 (0.13)	5.13 (0.22)	5.20 (0.14)	5.23 (0.14)

Adverse Events

Time Frame	Adverse events were collected from the first dose of treatment up until day 29 for the 0.1 mg/kg and 0.3 mg/kg SC treatment groups, up to 57 days for the 1 mg/kg and 3 mg/kg IV/SC groups and for up to 85 days for the 5 mg/kg and 10 mg/kg SC/IV groups.
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 SC		Placebo IV		Romosozumab 0.1 mg/kg SC		Romosozumab 0.3 mg/kg SC		Romosozumab 1.0 mg/kg SC		Romosozumab 10.0 mg/kg SC		Romosozumab 3.0 mg/kg SC		Romosozumab 5.0 mg/kg SC		Romosozumab 1.0 mg/kg IV		Romosozumab 5.0 mg/kg IV
Arm/Group Description	Participants received a single subcutaneous (SC) injection of matching placebo.		Participants received a single intravenous (IV) injection of matching placebo.		Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab.		Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab.		Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab.		Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab.		Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab.		Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab.		Participants received a single intravenous injection of 1.0 mg/kg romosozumab.		Participants received a single intravenous injection of 5.0 mg/kg romosozumab.
All Cause Mortality
	Placebo SC		Placebo IV		Romosozumab 0.1 mg/kg SC		Romosozumab 0.3 mg/kg SC		Romosozumab 1.0 mg/kg SC		Romosozumab 10.0 mg/kg SC		Romosozumab 3.0 mg/kg SC		Romosozumab 5.0 mg/kg SC		Romosozumab 1.0 mg/kg IV		Romosozumab 5.0 mg/kg IV
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo SC		Placebo IV		Romosozumab 0.1 mg/kg SC		Romosozumab 0.3 mg/kg SC		Romosozumab 1.0 mg/kg SC		Romosozumab 10.0 mg/kg SC		Romosozumab 3.0 mg/kg SC		Romosozumab 5.0 mg/kg SC		Romosozumab 1.0 mg/kg IV		Romosozumab 5.0 mg/kg IV
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Hepatobiliary disorders
HEPATITIS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo SC		Placebo IV		Romosozumab 0.1 mg/kg SC		Romosozumab 0.3 mg/kg SC		Romosozumab 1.0 mg/kg SC		Romosozumab 10.0 mg/kg SC		Romosozumab 3.0 mg/kg SC		Romosozumab 5.0 mg/kg SC		Romosozumab 1.0 mg/kg IV		Romosozumab 5.0 mg/kg IV
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/14 (64.3%)		2/4 (50%)		4/6 (66.7%)		4/6 (66.7%)		1/9 (11.1%)		5/6 (83.3%)		5/6 (83.3%)		6/9 (66.7%)		1/6 (16.7%)		2/6 (33.3%)
Blood and lymphatic system disorders
ANAEMIA	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
IRON DEFICIENCY ANAEMIA	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
Endocrine disorders
BASEDOW'S DISEASE	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Eye disorders
BLEPHARITIS	0/14 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
CONJUNCTIVITIS	0/14 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
ABDOMINAL PAIN UPPER	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
APHTHOUS STOMATITIS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
CONSTIPATION	1/14 (7.1%)		1/4 (25%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		2/9 (22.2%)		0/6 (0%)		1/6 (16.7%)
DIARRHOEA	0/14 (0%)		0/4 (0%)		2/6 (33.3%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
DRY MOUTH	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
DYSPEPSIA	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
LIP DRY	0/14 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
NAUSEA	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
ORAL DISCOMFORT	0/14 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
VOMITING	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
General disorders
ASTHENIA	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
AXILLARY PAIN	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
CHEST PAIN	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
INJECTION SITE ERYTHEMA	0/14 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		4/6 (66.7%)		2/6 (33.3%)		2/9 (22.2%)		0/6 (0%)		0/6 (0%)
INJECTION SITE HAEMORRHAGE	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		2/9 (22.2%)		0/6 (0%)		0/6 (0%)
INJECTION SITE REACTION	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
THIRST	0/14 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Infections and infestations
CELLULITIS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
ESCHERICHIA URINARY TRACT INFECTION	0/14 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
GASTROENTERITIS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
HORDEOLUM	0/14 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
NASOPHARYNGITIS	0/14 (0%)		0/4 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
TINEA PEDIS	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
UPPER RESPIRATORY TRACT INFECTION	2/14 (14.3%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
URINARY TRACT INFECTION	0/14 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
DECREASED APPETITE	0/14 (0%)		1/4 (25%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/14 (7.1%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
BACK PAIN	1/14 (7.1%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		2/6 (33.3%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
MUSCLE SPASMS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		2/9 (22.2%)		0/6 (0%)		0/6 (0%)
MUSCULOSKELETAL CHEST PAIN	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
MUSCULOSKELETAL DISCOMFORT	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
MUSCULOSKELETAL PAIN	2/14 (14.3%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
PAIN IN EXTREMITY	0/14 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
DIZZINESS	1/14 (7.1%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
HEADACHE	3/14 (21.4%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		2/6 (33.3%)		0/6 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/6 (0%)
SOMNOLENCE	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
Reproductive system and breast disorders
BREAST TENDERNESS	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		0/6 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/6 (16.7%)		0/6 (0%)
EPISTAXIS	0/14 (0%)		0/4 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
PHARYNGOLARYNGEAL PAIN	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
DERMATITIS	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
DERMATITIS CONTACT	1/14 (7.1%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)
Vascular disorders
HOT FLUSH	0/14 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		1/6 (16.7%)

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.