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

Amgen48 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Postmenopausal Osteopenia

Interventions

RomosozumabDRUG

Administered by subcutaneous injection

PlaceboDRUG

Administered by subcutaneous injection

Eligibility

Sex: ALLMin age: 45 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy males and females between 45 to 80 years of age * Postmenopausal females * Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine \[L1-L4\] or total evaluable vertebrae \[if fewer than L1-L4\] or total hip) * 25-hydroxyvitamin D ≥ 20 ng/mL * Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in) Exclusion Criteria: * Osteoporosis defined by bone mineral density (BMD) T-scores \< -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip * Diagnosed with any condition that would affect bone metabolism * Previous exposure to AMG 785

Outcomes

Primary Outcomes

Number of Participants With Adverse Events

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

Time frame: 169 days

Number of Participants Who Developed Antibodies to Romosozumab

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

Time frame: Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.

Secondary Outcomes

Time to Maximum Observed Concentration (Tmax) of Romosozumab

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

Time frame: Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

Maximum Observed Concentration (Cmax) of Romosozumab

Data from ClinicalTrials.gov

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Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab

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

Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab

Time frame: Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.

Accumulation Ratio (AR) for Romosozumab

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

Percent Change From Baseline in Bone Mineral Density of the Total Spine

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