Trial Outcomes & Findings for Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function (NCT NCT02521376)

Last Updated: 2019-07-26

Results Overview

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

56 participants

Primary outcome timeframe

0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Results posted on

2019-07-26

Participant Flow

Participants were enrolled at study sites in United States, New Zealand, and Germany. The first participant was screened on 16 November 2015. The last study visit occurred on 25 October 2017.

102 participants were screened.

Participant milestones

Participant milestones
Measure	Severe Hepatic Impairment Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Moderate Hepatic Impairment Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Mild Hepatic Impairment Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Overall Study STARTED	8	18	10	20
Overall Study COMPLETED	7	18	10	20
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Severe Hepatic Impairment Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Moderate Hepatic Impairment Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Mild Hepatic Impairment Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Overall Study Enrolled, But Not Treated	1	0	0	0

Baseline Characteristics

Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Severe Hepatic Impairment n=7 Participants Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Moderate Hepatic Impairment n=18 Participants Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Mild Hepatic Impairment n=10 Participants Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Healthy Control n=20 Participants Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Total n=55 Participants Total of all reporting groups
Age, Continuous	56 years STANDARD_DEVIATION 10.6 • n=99 Participants	59 years STANDARD_DEVIATION 8.5 • n=107 Participants	58 years STANDARD_DEVIATION 11.4 • n=206 Participants	56 years STANDARD_DEVIATION 9.3 • n=7 Participants	57 years STANDARD_DEVIATION 9.4 • n=31 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	4 Participants n=107 Participants	5 Participants n=206 Participants	5 Participants n=7 Participants	15 Participants n=31 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	14 Participants n=107 Participants	5 Participants n=206 Participants	15 Participants n=7 Participants	40 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	5 Participants n=107 Participants	3 Participants n=206 Participants	9 Participants n=7 Participants	20 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=99 Participants	13 Participants n=107 Participants	7 Participants n=206 Participants	11 Participants n=7 Participants	35 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants	4 Participants n=31 Participants
Race (NIH/OMB) White	7 Participants n=99 Participants	17 Participants n=107 Participants	9 Participants n=206 Participants	17 Participants n=7 Participants	50 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Region of Enrollment New Zealand	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	2 Participants n=31 Participants
Region of Enrollment United States	5 Participants n=99 Participants	17 Participants n=107 Participants	8 Participants n=206 Participants	19 Participants n=7 Participants	49 Participants n=31 Participants
Region of Enrollment Germany	1 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	4 Participants n=31 Participants

PRIMARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Population: Participants in the PK Analysis Set (all enrolled participants who received at least one dose of ENTO and had at least one evaluable PK concentration data value reported by the PK lab) with available data were analyzed. Healthy control participants may participate in more than one cohorts.

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Outcome measures

Outcome measures
Measure	Cohort 1: Moderate Hepatic Impairment Smoking n=9 Participants Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Moderate Hepatic Impairment Non-smoking n=9 Participants Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Smoking n=9 Participants Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Non-smoking n=9 Participants Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Severe Hepatic Impairment n=7 Participants Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Healthy Control n=7 Participants Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Mild Hepatic Impairment n=10 Participants Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Healthy Control n=10 Participants Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Pharmacokinetic (PK) Parameter: AUCtau of ENTO	1788.9 h*ng/mL Standard Deviation 771.30	7490.0 h*ng/mL Standard Deviation 3805.03	4081.5 h*ng/mL Standard Deviation 2464.77	3318.0 h*ng/mL Standard Deviation 1788.90	7036.0 h*ng/mL Standard Deviation 2814.95	3402.7 h*ng/mL Standard Deviation 1771.79	4071.9 h*ng/mL Standard Deviation 913.47	4123.0 h*ng/mL Standard Deviation 1874.33

PRIMARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Population: Participants in the PK Analysis Set with available data were analyzed. Healthy control participants may participate in more than one cohorts.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Outcome measures
Measure	Cohort 1: Moderate Hepatic Impairment Smoking n=9 Participants Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Moderate Hepatic Impairment Non-smoking n=9 Participants Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Smoking n=9 Participants Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Non-smoking n=9 Participants Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Severe Hepatic Impairment n=7 Participants Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Healthy Control n=7 Participants Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Mild Hepatic Impairment n=10 Participants Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Healthy Control n=10 Participants Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Pharmacokinetic (PK) Parameter: Cmax of ENTO	313.1 ng/mL Standard Deviation 122.39	1007.3 ng/mL Standard Deviation 480.63	582.3 ng/mL Standard Deviation 326.04	497.4 ng/mL Standard Deviation 292.67	837.7 ng/mL Standard Deviation 326.52	521.1 ng/mL Standard Deviation 280.65	569.8 ng/mL Standard Deviation 166.56	590.5 ng/mL Standard Deviation 326.08

SECONDARY outcome

Timeframe: Baseline up to Day 9 plus 30 days

Population: Safety Analysis Set included all randomized participants who received at least one dose of study drug.

TEAEs are defined as events that meet one of the following criteria: * Any adverse events (AEs) with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or * Any AEs leading to premature discontinuation of study drug.

Outcome measures

Outcome measures
Measure	Cohort 1: Moderate Hepatic Impairment Smoking n=7 Participants Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Moderate Hepatic Impairment Non-smoking n=18 Participants Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Smoking n=10 Participants Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Non-smoking n=20 Participants Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Severe Hepatic Impairment Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Mild Hepatic Impairment Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	14.3 percentage of participants	22.3 percentage of participants	30.0 percentage of participants	30.0 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Day 9 plus 30 days

Population: Participants in the Safety Analysis Set were analyzed.

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject.

Outcome measures

Outcome measures
Measure	Cohort 1: Moderate Hepatic Impairment Smoking n=7 Participants Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Moderate Hepatic Impairment Non-smoking n=18 Participants Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Smoking n=10 Participants Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 1: Healthy Control Matched to Non-smoking n=20 Participants Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Severe Hepatic Impairment Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 2: Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Mild Hepatic Impairment Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Cohort 3: Healthy Control Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	100.0 percentage of participants	88.9 percentage of participants	60.0 percentage of participants	50.0 percentage of participants	—	—	—	—

Adverse Events

Severe Hepatic Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Mild Hepatic Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Healthy Control

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Severe Hepatic Impairment n=7 participants at risk Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Moderate Hepatic Impairment n=18 participants at risk Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Mild Hepatic Impairment n=10 participants at risk Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Healthy Control n=20 participants at risk Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Gastrointestinal disorders Abdominal distension	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.6% 1/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	10.0% 2/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	10.0% 1/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.6% 1/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.0% 1/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Infected bite	14.3% 1/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.0% 1/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.0% 1/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Laceration	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	10.0% 1/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.6% 1/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	10.0% 1/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.6% 1/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	10.0% 1/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	20.0% 4/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Renal and urinary disorders Chromaturia	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.6% 1/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	14.3% 1/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/7 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/18 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.0% 1/20 • First dose date up to Day 9 plus 30 days Safety Analysis Set included all randomized participants who received at least one dose of study drug.