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

Osteoporosis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 162 Administered Subcutaneously to Japanese Postmenopausal Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03822078
• Other study ID #: 20030164
• Status: Completed
• Phase: Phase 1
• Start date: September 30, 2003
• Est. completion date: December 24, 2004

Study information

• Verified date: May 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 24, 2004
• Est. primary completion date: December 24, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Placebo
Administered by subcutaneous injection

Biological:
• Denosumab
Administered by subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr)		Baseline and day 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only).
Secondary	Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP)		Baseline and day 8, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, and 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only)
Secondary	Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)		Baseline and day 2, 3, 5, 8, 15, 29, 57, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only)

External Links

•   AmgenTrials clinical trials website