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

Primary Purpose

Osteoporosis

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Placebo

Denosumab

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Postmenopausal, Denosumab

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)Does not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Denosumab

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events

Secondary Outcome Measures

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

Maximum Observed Concentration of Denosumab (Cmax)

Time to Maximum Observed Concentration (Tmax) of Denosumab

Apparent Clearance (CL/F) of Denosumab

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

Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr)

Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP)

Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

Full Information

NCT ID

NCT03822078

First Posted

January 28, 2019

Last Updated

May 21, 2019

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT03822078

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

September 30, 2003 (Actual)

Primary Completion Date

December 24, 2004 (Actual)

Study Completion Date

December 24, 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoporosis

Keywords

Postmenopausal, Denosumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Denosumab

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered by subcutaneous injection

Intervention Type

Biological

Intervention Name(s)

Denosumab

Other Intervention Name(s)

AMG 162, Prolia

Intervention Description

Administered by subcutaneous injection

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events

Time Frame

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 Outcome Measure Information:

Title

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

Time Frame

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

Title

Maximum Observed Concentration of Denosumab (Cmax)

Time Frame

Title

Time to Maximum Observed Concentration (Tmax) of Denosumab

Time Frame

Title

Apparent Clearance (CL/F) of Denosumab

Time Frame

Title

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

Time Frame

Title

Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr)

Time Frame

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).

Title

Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP)

Time Frame

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)

Title

Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

Time Frame

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)

10. Eligibility

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

21871589

Citation

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.

Results Reference

background

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

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

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