Trial Outcomes & Findings for The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam (NCT NCT01221727)

Last Updated: 2018-08-07

Results Overview

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Results posted on

2018-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	Midazolam With Denosumab 2 mg oral dose of Midazolam on Day 1 and Day 16, 60 mg subcutaneous dose of Denosumab on Day 2	Midazolam Only 2 mg oral dose of Midazolam on Day 1 and Day 16.
Overall Study STARTED	21	9
Overall Study Treated	19	8
Overall Study COMPLETED	18	8
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Midazolam With Denosumab 2 mg oral dose of Midazolam on Day 1 and Day 16, 60 mg subcutaneous dose of Denosumab on Day 2	Midazolam Only 2 mg oral dose of Midazolam on Day 1 and Day 16.
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Midazolam With Denosumab n=19 Participants 2 mg oral dose of Midazolam on Day 1 and Day 16, 60 mg subcutaneous dose of Denosumab on Day 2. Out of 21 subjects enrolled and randomized, 19 subjects received investigation product.	Midazolam Only n=8 Participants 2 mg oral dose of Midazolam on Day 1 and Day 16. Out of 9 subjects enrolled and randomized, 8 subjects received investigation product.	Total n=27 Participants Total of all reporting groups
Age, Continuous	64.42 years STANDARD_DEVIATION 6.16 • n=93 Participants	66.25 years STANDARD_DEVIATION 5.34 • n=4 Participants	64.96 years STANDARD_DEVIATION 5.89 • n=27 Participants
Age, Customized <65 years	7 Participants n=93 Participants	3 Participants n=4 Participants	10 Participants n=27 Participants
Age, Customized >=65 years and <75 years	12 Participants n=93 Participants	4 Participants n=4 Participants	16 Participants n=27 Participants
Age, Customized >=75 years	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Sex: Female, Male Female	19 Participants n=93 Participants	8 Participants n=4 Participants	27 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=93 Participants	4 Participants n=4 Participants	11 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=93 Participants	4 Participants n=4 Participants	16 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	6 Participants n=4 Participants	23 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Population: The analysis set will contain all subjects from Midazolam with Denosumab group for whom the primary endpoint PK parameters (AUC(0-t), AUC(0-inf) and Cmax) can be estimated for both treatment periods.

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 unitless Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only) AUC (0-t)	1.10 unitless Interval 0.94 to 1.29
Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only) AUC (0-inf)	1.12 unitless Interval 0.95 to 1.31

PRIMARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 area Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group AUC (0-t) Subject: Inter-subject	0.19 ng*hr/mL Standard Deviation 0.079
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group AUC (0-t) Residual: Intra-subject	0.07 ng*hr/mL Standard Deviation 0.025
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group AUC (0-inf) Subject: Inter-subject	0.21 ng*hr/mL Standard Deviation 0.085
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group AUC (0-inf) Residual: Intra-subject	0.08 ng*hr/mL Standard Deviation 0.027

PRIMARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 concentration Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group Cmax Subject: Inter-subject	0.15 ng/mL Standard Deviation 0.064
Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group Cmax Residual: Intra-subject	0.07 ng/mL Standard Deviation 0.023

PRIMARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 unitless Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)	1.11 unitless Interval 0.96 to 1.29

SECONDARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Population: The analysis set will contain all subjects from Midazolam only group for whom the primary endpoint PK parameters (AUC(0-t), AUC(0-inf) and Cmax) can be estimated for both treatment periods.

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=8 unitless Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only) AUC (0-t)	0.98 unitless Interval 0.83 to 1.15
Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only) AUC (0-inf)	0.98 unitless Interval 0.84 to 1.15

SECONDARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=8 area Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group AUC (0-t) Subject: Inter-subject	0.27 ng*hr/mL Standard Deviation 0.155
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group AUC (0-t) Residual: Intra-subject	0.03 ng*hr/mL Standard Deviation 0.016
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group AUC (0-inf) Subject: Inter-subject	0.31 ng*hr/mL Standard Deviation 0.175
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group AUC (0-inf) Residual: Intra-subject	0.03 ng*hr/mL Standard Deviation 0.015

SECONDARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=8 concentration Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group Cmax Subject: Inter-subject	0.23 ng/mL Standard Deviation 0.143
Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group Cmax Residual: Intra-subject	0.06 ng/mL Standard Deviation 0.035

SECONDARY outcome

Timeframe: Baseline (day 2 pre-dose) to day 16

Population: Serum Denosumab will be collected for subjects in Midazolam with Denosumab group only. The analysis set will contain subjects in Midazolam with Denosumab group who received denosumab administration and for whom serum Denosumab concentrations are determinable when assessed.

This table summarizes serum Denosumab for Midazolam with Denosumab group. The Lower Limit Of Quantification (LLOQ) is 20 ng/mL. On Day 2 (pre-dose), the true value is below LLOQ, and is treated as 0 in the analysis.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 concentration Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Summary of Serum Denosumab Concentration Day 2 (Pre-dose)	0 ng/mL Standard Deviation NA All the pre-dose concentration measurements are below LLOQ, and were treated as 0 in the analysis. Therefore, the true standard deviation is not able to be calculated.
Summary of Serum Denosumab Concentration Day 16 (0hr)	5820 ng/mL Standard Deviation 1800
Summary of Serum Denosumab Concentration Day 17 (24hr)	5500 ng/mL Standard Deviation 1940

SECONDARY outcome

Timeframe: Baseline (day 2 pre-dose) to day 16

Population: Serum CTX will be collected for Midazolam with Denosumab group only. The PD analysis set will contain subjects in Midazolam with Denosumab group who received denosumab administration and for whom serum CTX concentrations are determinable on when assessed.

This table summarizes serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 concentration Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Summary of Serum C-Telopeptide Concentration Baseline (day 2 pre-dose)	0.4655 ng/mL Inter-Quartile Range 0.0698 • Interval 0.339 to 0.629
Summary of Serum C-Telopeptide Concentration Day 16	0.0606 ng/mL Inter-Quartile Range 0.0030 • Interval 0.0483 to 0.0662
Summary of Serum C-Telopeptide Concentration Change from baseline to Day 16	-0.4079 ng/mL Inter-Quartile Range 0.0702 • Interval -0.5752 to -0.2712

SECONDARY outcome

Timeframe: Baseline (day 2 pre-dose) to day 16

This table summarizes percent change from baseline to day 16 for serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=18 percentage Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration	-87.52 percentage Interval -91.45 to -80.01

SECONDARY outcome

Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.

Outcome measures

Outcome measures
Measure	Midazolam With Denosumab n=8 unitless Subjects received 2 mg oral dose of Midazolam on day 1 (serving as a reference point) and day 16 (serving as a test point), and 60 mg subcutaneous dose of Denosumab on day 2
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)	1.05 unitless Interval 0.82 to 1.33

Adverse Events

Midazolam With Denosumab Group With Midazolam 2mg on Day 1

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Midazolam With Denosumab Group With Denosumab 60mg on Day 2-15

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Midazolam With Denosumab Group With Midazolam 2mg on Day 16

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Midazolam Only Group With Midazolam 2mg on Day 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Midazolam Only Group With Midazolam 2mg on Day 2-15

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Midazolam Only Group With Midazolam 2mg on Day 16

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Midazolam With Denosumab Group With Midazolam 2mg on Day 1 n=19 participants at risk	Midazolam With Denosumab Group With Denosumab 60mg on Day 2-15 n=18 participants at risk	Midazolam With Denosumab Group With Midazolam 2mg on Day 16 n=18 participants at risk	Midazolam Only Group With Midazolam 2mg on Day 1 n=8 participants at risk	Midazolam Only Group With Midazolam 2mg on Day 2-15 n=8 participants at risk	Midazolam Only Group With Midazolam 2mg on Day 16 n=8 participants at risk
Gastrointestinal disorders Constipation	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 1/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chills	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Injection site pain	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.1% 2/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Laceration	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dizziness	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.1% 2/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 1/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 3/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 1/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Presyncope	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Somnolence	36.8% 7/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	38.9% 7/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	25.0% 2/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Pollakiuria	5.3% 1/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/19 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 1/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/18 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/8 • 47 days The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee 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 multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER