A Single-dose Study Evaluating Romosozumab (AMG 785) in Healthy Postmenopausal Japanese and Non-Japanese Women

A Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Postmenopausal Japanese Women

The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.

Study Overview

• Status: Completed
• Conditions: Osteopenia
• Intervention / Treatment: Drug: Placebo; Drug: Romosozumab

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Japanese subjects must be first (4 grandparents, biologic parents and subject born in Japan), second (4 grandparents and biological parents born in Japan) or third (4 grandparents born in Japan) generation Japanese
• Body mass index ≤ 25 kg/m², inclusive at screening
• Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy) as documented in medical history (verified with an operative note, if available)

Exclusion Criteria:

• Osteoporosis, as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck ≤ -2.5
• History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis;
• Diagnosed with any condition that will affect bone metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Romosozumab; Japanese women in cohorts 1, 2, and 4 will receive a single dose of 1, 3, or 5 mg/kg romosozumab. Non-Japanese women in cohort 3 will receive a single dose of 3 mg/kg romosozumab.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; EVENITY™
PLACEBO_COMPARATOR: Placebo; Participants will receive a single dose of placebo.	Drug: Placebo; Administered by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	A serious adverse event (SAE) is defined as an adverse event that; is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product.	Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments.
Number of Participants Who Developed Anti-romosozumab Binding Antibodies	Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.	Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo)
Serum Calcium Levels		Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Serum Intact Parathyroid Hormone (iPTH) Levels		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Maximum Percent Change From Baseline in Serum C-telopeptide (CTX)		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Percent Change From Baseline in Sclerostin		Baseline and days 12, 29, 43, 57, 71, and 85
Time to Maximum Observed Concentration of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Maximum Observed Concentration of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Apparent Clearance (CL/F) of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 3, 2010
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: April 8, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (ESTIMATE): April 9, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Japanese; Phase 1; Amgen; Postmenopausal
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: 20090378