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

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ClinicalTrials.gov Identifier: NCT03822078
Recruitment Status : Completed
First Posted : January 30, 2019
Results First Posted : July 24, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Sequential Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Osteoporosis
Interventions Drug: Placebo
Biological: Denosumab
Enrollment 45
Recruitment Details This study was conducted at one clinical center in Japan.
Pre-assignment Details The study consisted of 5 dose cohorts of 8 participants. Within each dose cohort 6 participants were randomly assigned to receive denosumab and 2 participants to receive placebo.
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description Participants received a single subcutaneous injection of placebo to denosumab on day 1. Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Period Title: Overall Study
Started 12 6 6 8 7 6
Received Study Drug 10 6 6 6 6 6
Completed 10 6 6 6 6 6
Not Completed 2 0 0 2 1 0
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg Total
Hide Arm/Group Description Participants received a single subcutaneous injection of placebo to denosumab on day 1. Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. Total of all reporting groups
Overall Number of Baseline Participants 12 6 6 8 7 6 45
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 6 participants 6 participants 8 participants 7 participants 6 participants 45 participants
59.83  (2.86) 59.67  (2.34) 59.50  (3.39) 58.88  (3.80) 56.43  (3.95) 58.67  (2.34) 58.91  (3.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 6 participants 6 participants 8 participants 7 participants 6 participants 45 participants
Female
12
 100.0%
6
 100.0%
6
 100.0%
8
 100.0%
7
 100.0%
6
 100.0%
45
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 6 participants 6 participants 8 participants 7 participants 6 participants 45 participants
Japanese
12
 100.0%
6
 100.0%
6
 100.0%
8
 100.0%
7
 100.0%
6
 100.0%
45
 100.0%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of placebo to denosumab on day 1.
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
6
  60.0%
2
  33.3%
3
  50.0%
5
  83.3%
6
 100.0%
5
  83.3%
Serious adverse events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Treatment-related adverse events
4
  40.0%
0
   0.0%
1
  16.7%
3
  50.0%
4
  66.7%
4
  66.7%
Discontinuation due to adverse events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Deaths on study
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Area Under the Serum Concentration Time Curve From Time 0 to Time of Last Quantifiable Serum Concentration (AUC0-t) of Denosumab
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received denosumab
Arm/Group Title Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: μg*day/mL
2.06  (0.53) 15.2  (6.7) 84.3  (20.1) 481  (131) 1790  (650)
3.Secondary Outcome
Title Maximum Observed Concentration of Denosumab (Cmax)
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
99.6  (25.8) 492  (166) 1910  (658) 8690  (2170) 27400  (7880)
4.Secondary Outcome
Title Time to Maximum Observed Concentration (Tmax) of Denosumab
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received denosumab
Arm/Group Title Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 6 6 6 6 6
Median (Full Range)
Unit of Measure: days
7.0
(7 to 10)
12.0
(7 to 21)
14.0
(7 to 21)
14.0
(10 to 21)
14.0
(14 to 42)
5.Secondary Outcome
Title Apparent Clearance (CL/F) of Denosumab
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received denosumab
Arm/Group Title Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: mL/day/kg
15.3  (4.2) 8.31  (4.97) 3.72  (0.89) 2.20  (0.56) 1.85  (0.58)
6.Secondary Outcome
Title Mean Residence Time (MRT) From Time 0 to Time of Last Quantifiable Serum Concentration
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received denosumab
Arm/Group Title Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: days
15.5  (4.7) 22.5  (3.9) 33.6  (5.8) 42.6  (7.0) 51.4  (5.8)
7.Secondary Outcome
Title Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr)
Hide Description [Not Specified]
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).
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants with available data at each time point
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of placebo to denosumab on day 1.
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Error)
Unit of Measure: percent change
Day 2 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
12  (11) 6  (4) -25  (8) -22  (11) -40  (7) -64  (4)
Day 3 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
19  (5) -6  (7) -30  (5) -40  (11) -51  (8) -60  (3)
Day 4 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
7  (6) -18  (9) -37  (16) -48  (11) -55  (6) -62  (5)
Day 5 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
23  (10) -12  (12) -44  (5) -51  (8) -53  (8) -66  (6)
Day 6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
9  (7) -1  (18) -53  (8) -62  (7) -59  (6) -72  (4)
Day 8 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
16  (7) -12  (13) -55  (7) -64  (5) -57  (7) -64  (10)
Day 11 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3  (8) -36  (5) -67  (5) -65  (7) -69  (6) -79  (3)
Day 15 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
4  (3) -51  (4) -68  (4) -71  (5) -71  (5) -77  (5)
Day 22 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1  (5) -41  (4) -71  (6) -70  (7) -70  (5) -82  (3)
Day 29 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1  (5) -39  (5) -68  (3) -67  (6) -64  (7) -77  (4)
Day 43 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1  (5) -33  (6) -67  (4) -68  (7) -69  (8) -81  (4)
Day 57 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0  (8) -14  (3) -59  (6) -64  (8) -56  (10) -79  (6)
Day 71 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-5  (7) -23  (6) -48  (10) -65  (6) -68  (5) -82  (3)
Day 85 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
8  (7) 4  (8) -48  (12) -58  (9) -68  (4) -83  (4)
Day 99 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1  (6) 4  (6) -37  (15) -64  (5) -72  (4) -77  (10)
Day 113 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-5  (6) 3  (4) -30  (15) -53  (10) -77  (3) -84  (2)
Day 141 Number Analyzed 6 participants 0 participants 0 participants 6 participants 6 participants 6 participants
-7  (9) -51  (5) -62  (5) -81  (3)
Day 169 Number Analyzed 6 participants 0 participants 6 participants 6 participants 6 participants 6 participants
-15  (6) 6  (14) -41  (11) -48  (9) -78  (5)
Day 197 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
-3  (5) -47  (8) -79  (4)
Day 225 Number Analyzed 5 participants 0 participants 1 participants 5 participants 6 participants 6 participants
-7  (11) 42.0 -30  (4) -20  (17) -70  (4)
Day 253 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
-13  (10) -25  (14) -62  (5)
Day 281 Number Analyzed 0 participants 0 participants 0 participants 4 participants 0 participants 0 participants
-13  (8)
Day 309 Number Analyzed 0 participants 0 participants 0 participants 0 participants 4 participants 6 participants
-19  (13) -23  (12)
8.Secondary Outcome
Title Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP)
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants with available data at each time point
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of placebo to denosumab on day 1.
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Error)
Unit of Measure: percent change
Day 8 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.4  (2.8) -6.9  (5.9) 16.6  (4.7) 7.1  (2.0) -0.5  (5.1) 3.1  (6.4)
Day 15 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-2.1  (1.4) 1.1  (3.1) 8.6  (2.0) 13.2  (2.0) 5.6  (5.9) 11.5  (7.8)
Day 22 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1.1  (2.8) 12.7  (3.1) 5.8  (2.3) 7.8  (3.8) 7.0  (5.3) 9.7  (5.8)
Day 29 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
5.3  (2.9) 8.9  (3.6) 11.0  (3.5) -0.7  (2.8) 5.8  (4.2) -0.4  (4.5)
Day 43 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3.6  (3.1) -2.3  (2.8) -7.6  (4.3) -20.3  (3.2) -10.2  (4.0) -14.7  (2.6)
Day 57 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
2.7  (1.6) -5.9  (5.1) -19.2  (2.8) -33.1  (3.1) -21.0  (4.9) -24.0  (2.6)
Day 71 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.9  (3.0) -5.5  (4.8) -29.0  (5.7) -41.0  (2.2) -36.1  (5.2) -33.9  (4.7)
Day 85 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1.3  (2.2) -7.9  (6.3) -27.2  (6.1) -47.7  (3.2) -42.1  (4.2) -43.9  (1.9)
Day 99 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1.7  (3.2) -13.1  (3.3) -33.4  (5.5) -49.4  (3.0) -44.0  (5.5) -47.5  (2.7)
Day 113 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3.1  (2.3) -0.5  (7.1) -32.6  (5.4) -54.2  (2.6) -49.7  (5.1) -51.4  (2.6)
Day 141 Number Analyzed 6 participants 0 participants 0 participants 6 participants 6 participants 6 participants
-0.2  (4.9) -57.2  (2.6) -50.7  (6.9) -52.9  (3.8)
Day 169 Number Analyzed 6 participants 0 participants 6 participants 6 participants 6 participants 6 participants
3.1  (4.3) -33.9  (7.8) -52.9  (2.5) -50.1  (4.6) -53.7  (2.9)
Day 197 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
8.6  (5.8) -43.9  (8.6) -52.5  (2.7)
Day 225 Number Analyzed 5 participants 0 participants 1 participants 5 participants 6 participants 6 participants
4.6  (3.0) 19.5 -37.1  (4.4) -35.1  (8.5) -48.4  (3.6)
Day 253 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
11.7  (6.5) -31.9  (9.7) -44.0  (4.1)
Day 281 Number Analyzed 0 participants 0 participants 0 participants 4 participants 0 participants 0 participants
-10.7  (6.1)
Day 309 Number Analyzed 0 participants 0 participants 0 participants 0 participants 4 participants 6 participants
-21.0  (14.7) -26.8  (4.8)
9.Secondary Outcome
Title Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants with available data at each time point
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg
Hide Arm/Group Description:
Participants received a single subcutaneous injection of placebo to denosumab on day 1.
Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1.
Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Error)
Unit of Measure: percent change
Day 2 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
6.9  (8.7) 2.4  (13.0) 10.1  (14.1) 44.0  (13.0) 40.9  (19.5) 129.0  (25.2)
Day 3 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.2  (6.1) 28.9  (9.7) 15.0  (18.8) 71.7  (15.8) 60.7  (21.7) 146.1  (46.0)
Day 5 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-3.9  (6.0) 47.6  (12.2) 51.8  (17.9) 114.2  (27.2) 103.1  (41.8) 262.1  (61.9)
Day 8 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.7  (8.9) 37.7  (20.4) 76.9  (20.7) 182.4  (40.2) 163.7  (38.4) 353.6  (92.4)
Day 15 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
11.2  (8.9) 91.5  (8.2) 117.3  (33.4) 146.4  (29.0) 109.4  (36.3) 203.2  (27.2)
Day 29 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
5.1  (7.7) 97.2  (23.8) 110.9  (40.7) 99.2  (16.8) 70.4  (28.3) 215.2  (79.4)
Day 57 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
5.3  (8.3) 64.6  (18.4) 120.5  (35.5) 98.0  (17.9) 90.9  (20.8) 177.0  (36.8)
Day 85 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
17.1  (10.2) 11.9  (9.6) 36.6  (24.5) 76.9  (20.2) 64.4  (18.4) 170.5  (40.8)
Day 99 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
5.6  (7.4) 19.9  (10.5) 46.4  (31.1) 79.6  (13.9) 44.0  (10.9) 178.5  (93.3)
Day 113 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1.2  (10.2) 3.9  (15.4) 29.5  (32.8) 38.5  (13.5) 46.5  (10.5) 155.7  (44.5)
Day 141 Number Analyzed 6 participants 0 participants 0 participants 6 participants 6 participants 6 participants
-3.8  (13.9) 16.9  (11.1) 22.8  (16.6) 175.4  (81.3)
Day 169 Number Analyzed 6 participants 0 participants 6 participants 6 participants 6 participants 6 participants
-7.9  (5.3) -16.7  (10.6) 19.7  (8.2) 21.9  (16.1) 90.2  (27.6)
Day 197 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
-14.9  (5.4) 17.0  (9.8) 100.7  (42.1)
Day 225 Number Analyzed 5 participants 0 participants 1 participants 5 participants 6 participants 6 participants
-5.1  (14.1) 15.9 -30.9  (5.0) 6.2  (12.3) 151.4  (83.5)
Day 253 Number Analyzed 4 participants 0 participants 0 participants 0 participants 6 participants 6 participants
8.5  (12.6) 10.9  (18.1) 70.8  (31.5)
Day 281 Number Analyzed 0 participants 0 participants 0 participants 4 participants 0 participants 0 participants
-26.1  (9.4)
Day 309 Number Analyzed 0 participants 0 participants 0 participants 0 participants 4 participants 6 participants
16.6  (24.9) 33.8  (11.9)
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.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg Denosumab Total
Hide Arm/Group Description Participants received a single subcutaneous injection of placebo to denosumab on day 1. Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. All participants received a single subcutaneous injection of denosumab on day 1.
All-Cause Mortality
Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg Denosumab Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg Denosumab Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/30 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Denosumab 0.03 mg/kg Denosumab 0.1 mg/kg Denosumab 0.3 mg/kg Denosumab 1.0 mg/kg Denosumab 3.0 mg/kg Denosumab Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/10 (60.00%)   2/6 (33.33%)   3/6 (50.00%)   5/6 (83.33%)   6/6 (100.00%)   5/6 (83.33%)   21/30 (70.00%) 
Cardiac disorders               
ATRIAL FIBRILLATION  1  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
Ear and labyrinth disorders               
SENSATION OF BLOCK IN EAR  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
TINNITUS  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
Eye disorders               
BLEPHAROSPASM  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
CONJUNCTIVAL HAEMORRHAGE  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
CONJUNCTIVITIS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
Gastrointestinal disorders               
ABDOMINAL PAIN  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
CHEILITIS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
DIARRHOEA  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/30 (3.33%) 
GASTRITIS  1  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
GINGIVAL BLEEDING  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
LIP BLISTER  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
STOMACH DISCOMFORT  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
STOMATITIS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
General disorders               
CHEST DISCOMFORT  1  0/10 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  2/30 (6.67%) 
CHEST PAIN  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
FATIGUE  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/30 (3.33%) 
INJECTION SITE ERYTHEMA  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
INJECTION SITE HAEMORRHAGE  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
INJECTION SITE PAIN  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  3/30 (10.00%) 
MALAISE  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
Immune system disorders               
SEASONAL ALLERGY  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
Infections and infestations               
BRONCHITIS ACUTE  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/30 (3.33%) 
HERPES ZOSTER  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
NASOPHARYNGITIS  1  3/10 (30.00%)  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  5/6 (83.33%)  1/6 (16.67%)  9/30 (30.00%) 
PERIODONTAL INFECTION  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
Injury, poisoning and procedural complications               
BLISTER  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
CONTUSION  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
THERMAL BURN  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  2/30 (6.67%) 
Investigations               
HEPATIC ENZYME INCREASED  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
Musculoskeletal and connective tissue disorders               
ARTHRALGIA  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
BACK PAIN  1  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
MUSCLE FATIGUE  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/30 (3.33%) 
MYALGIA  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
PERIARTHRITIS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
SPONDYLOSIS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
Nervous system disorders               
DIZZINESS  1  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
HEADACHE  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/30 (6.67%) 
HYPOAESTHESIA  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
Respiratory, thoracic and mediastinal disorders               
RHINITIS ALLERGIC  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
RHINORRHOEA  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  3/30 (10.00%) 
Skin and subcutaneous tissue disorders               
DERMATITIS  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
DERMATITIS CONTACT  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/30 (3.33%) 
ECZEMA  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  2/30 (6.67%) 
HAEMORRHAGE SUBCUTANEOUS  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/30 (3.33%) 
PRURITUS  1  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/30 (0.00%) 
RASH  1  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/30 (3.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 7.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
EMail: medinfo@amgen.com
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03822078     History of Changes
Other Study ID Numbers: 20030164
First Submitted: January 28, 2019
First Posted: January 30, 2019
Results First Submitted: May 21, 2019
Results First Posted: July 24, 2019
Last Update Posted: July 24, 2019