Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Denosumab (AMG 162) in Japanese Postmenopausal Women

NCT03822078 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 20030164
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective was to evaluate the safety and tolerability of denosumab (AMG 162) after a single subcutaneous administration in Japanese postmenopausal women.

Conditions

Osteoporosis

Keywords

Postmenopausal; Denosumab

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  From day 1 up to 4 months for participants assigned to the 0.03 or 0.1 mg/kg dose cohorts, up to 6 months for participants assigned to the 0.3 mg/kg dose cohort and for up to 9 months for participants assigned to the 1.0 or 3.0 mg/kg dose cohorts

Secondary Outcomes (8)

• Area Under the Serum Concentration Time Curve From Time 0 to Time of Last Quantifiable Serum Concentration (AUC0-t) of Denosumab

  Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts

• Maximum Observed Concentration of Denosumab (Cmax)

  Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts

• Time to Maximum Observed Concentration (Tmax) of Denosumab

  Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts

• Apparent Clearance (CL/F) of Denosumab

  Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts

• Mean Residence Time (MRT) From Time 0 to Time of Last Quantifiable Serum Concentration

  Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants received a single subcutaneous injection of placebo to denosumab on day 1.

Drug: Placebo

Denosumab

EXPERIMENTAL

Participants received a single subcutaneous dose of denosumab on day 1. Doses included 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg.

Biological: Denosumab

Interventions

Placebo DRUG

Administered by subcutaneous injection

Placebo

Denosumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 162, Prolia

Denosumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ambulatory women between the ages of 40 and 64 years, inclusive
• postmenopausal, defined as amenorrheic for at least 24 months
• clinically acceptable physical exam
• clinical laboratory tests (complete blood count \[CBC\], blood chemistries, urinalysis) within normal limits or clinically acceptable to the investigator/sponsor at the time of screening with the exception of aspartate transaminase (AST) and alkaline phosphatase (ALT), which must be \< 1.25 times the upper limit of normal, or gamma-glutamyl transpeptidase (GGT), which must be \< 1.5 times the upper limit of normal
• normal or clinically acceptable electrocardiogram (ECG) (12-lead reporting ventricular rate and PR, QRS, QT, and QTc intervals)
• body mass index between 17 and 27
• willing to sign an approved informed consent form before any study-specific assessments and oral consultations are performed

You may not qualify if:

• administration of medications within 6 months before investigational product administration that are known to effect bone metabolism, including but not limited to the following: calcitonin, parathyroid hormone (or any derivative), supplemental vitamin D (\> 1000 IU/day), glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the date of informed consent were allowed), anabolic steroids, calcitriol and available analogues, diuretics
• administration of the following medications within 12 months before study drug administration: bisphosphonates, fluoride for osteoporosis
• diagnosed with any condition that affects bone metabolism
• greatly differing levels of physical activity compared with the 6 months before investigational product administration or constant levels of intense physical activities
• routine alcohol intake of ≥ 2 drinks/day, on average, within 6 months of investigational product administration
• known sensitivity to any drugs
• positive test results for hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus antigen/antibody, syphilis
• receiving or received any investigational drug (or was currently using an investigational device) within 4 months before receiving investigational product
• donated any amount of blood within 16 weeks, or over 400 mL (Note: not 400 mL but 200 mL, for the subjects who were to be enrolled into cohorts 4 or 5) within 1 year of the start day of screening
• subject had previously entered this study
• any other condition that might have reduced the chance of obtaining data (eg, known poor compliance) required by the protocol or that might have compromised the ability to give truly informed consent

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Kumagai Y, Hasunuma T, Padhi D. A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women. Bone. 2011 Nov;49(5):1101-7. doi: 10.1016/j.bone.2011.08.007. Epub 2011 Aug 12.

  PMID: 21871589 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: September 30, 2003
• Primary Completion: December 24, 2004
• Study Completion: December 24, 2004
• Last Updated: July 24, 2019
• Results First Posted: July 24, 2019

Record last verified: 2019-05