Trial Outcomes & Findings for A Study of the Effect of a Moderate CYP3A Inducer Efavirenz on Quizartinib Pharmacokinetics in Healthy Participants (NCT NCT04459598)

NCT ID: NCT04459598

Last Updated: 2022-06-28

Results Overview

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study. Cmax was assessed for Quizartinib and active metabolite AC886.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
• Results posted on: 2022-06-28

Participant Flow

A total of 32 participants who met all inclusion criteria and no exclusion criteria were enrolled from 19 Aug 2020 to 14 Oct 2020 at 1 clinic in the United States.

This study consisted of two treatment periods. Following a Screening Period of 21 days, eligible participants were randomized in a 1:1 ratio to 1 of 2 treatment groups. Treatment Group A received efavirenz once daily on Day 1 and continued the regimen through Day 35 and a single dose of quizartinib on Day 15. Treatment Group B received a single dose of quizartinib on Day 1.

Participant milestones

Measure	Efavirenz 600 mg + Quizartinib 60 mg Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Overall Study STARTED	16	16
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Efavirenz 600 mg + Quizartinib 60 mg Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Overall Study Adverse Event	1	1

Baseline Characteristics

A Study of the Effect of a Moderate CYP3A Inducer Efavirenz on Quizartinib Pharmacokinetics in Healthy Participants

Baseline characteristics by cohort

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=16 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	40 years STANDARD_DEVIATION 10.05 • n=5 Participants	38.7 years STANDARD_DEVIATION 10.22 • n=7 Participants	39.6 years STANDARD_DEVIATION 10.01 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study. Cmax was assessed for Quizartinib and active metabolite AC886.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz Quizartinib	130.0 ng/mL Standard Deviation 36.1	238.0 ng/mL Standard Deviation 76.9
Maximum Plasma Concentration (Cmax) Following Single Dose of Quizartinib With or Without Efavirenz AC886	11.0 ng/mL Standard Deviation 5.35	34.4 ng/mL Standard Deviation 18.2

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study. Tmax was assessed for Quizartinib and active metabolite AC886.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz Quizartinib	2.0 hours Interval 2.0 to 4.0	4.0 hours Interval 2.0 to 4.2
Time to Maximum Plasma Concentration (Tmax) Following Single Dose of Quizartinib With or Without Efavirenz AC886	4.0 hours Interval 2.0 to 4.0	4.0 hours Interval 4.0 to 24.0

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method and was calculated using non-compartmental analysis. AUClast was assessed for Quizartinib and active metabolite AC886.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) Following Single Dose of Quizartinib With or Without Efavirenz Quizartinib	2730 ng*h/mL Standard Deviation 1160	23600 ng*h/mL Standard Deviation 8420
Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) Following Single Dose of Quizartinib With or Without Efavirenz AC886	185 ng*h/mL Standard Deviation 177	4110 ng*h/mL Standard Deviation 1320

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data. Data from participants where AUCinf based on extrapolation was greater than 20% was also excluded from the Efavirenz 600 mg + Quizartinib 60 mg group and Quizartinib 60 mg group.

Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and was calculated using non-compartmental analysis. AUCinf was assessed for Quizartinib and active metabolite AC886.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz AC886	208 ng*h/mL Standard Deviation 183	4540 ng*h/mL Standard Deviation 1410
Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) Following Single Dose of Quizartinib With or Without Efavirenz Quizartinib	2760 ng*h/mL Standard Deviation 1170	26000 ng*h/mL Standard Deviation 9880

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis. AUClast was assessed for Quizartinib and active metabolite AC886. Half-life (t1/2) was assessed for Quizartinib and active metabolite AC886.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz AC886	11.9 hours Standard Deviation 5.5	135 hours Standard Deviation 33.5
Terminal Half-Life (t1/2) Following Single Dose of Quizartinib With or Without Efavirenz Quizartinib	23.8 hours Standard Deviation 7.4	136 hours Standard Deviation 40.1

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data. Data from participants where AUCinf based on extrapolation was greater than 20% was also excluded from MPR AUCinf.

AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz MPR AUClast	0.0675 ratio Standard Deviation 0.0403	0.186 ratio Standard Deviation 0.0753
Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib With or Without Efavirenz MPR AUCinf	0.0762 ratio Standard Deviation 0.0395	0.1880 ratio Standard Deviation 0.0777

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz	12.210 L/h Standard Deviation 7.6937	1.1849 L/h Standard Deviation 0.51388

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose

Population: Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set except for 1 participant from the Efavirenz 600 mg + Quizartinib 60 mg group due to insufficient data.

Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=15 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib With or Without Efavirenz	359.9 L Standard Deviation 102.23	214.9 L Standard Deviation 59.82

SECONDARY outcome

Timeframe: Baseline up to 30 days post last dose, up to approximately 2 months

Population: TEAEs were assessed using the Safety Analysis Set.

A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.

Outcome measures

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=16 Participants Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 Participants Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib With or Without Efavirenz	13 Participants	5 Participants

Adverse Events

Efavirenz 600 mg + Quizartinib 60 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Quizartinib 60 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Efavirenz 600 mg + Quizartinib 60 mg n=16 participants at risk Participants who received efavirenz 600 mg once daily (QD) for 34 days and a single, oral dose of quizartinib 60 mg on Day 15 concurrently with efavirenz.	Quizartinib 60 mg n=16 participants at risk Participants who received a single, oral dose of quizartinib 60 mg on Day 1.
Nervous system disorders Headache	37.5% 6/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	12.5% 2/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Nervous system disorders Dizziness	31.2% 5/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Nervous system disorders Paraesthesia	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Nervous system disorders Disturbance in attention	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Nervous system disorders Dizziness postural	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Nausea	18.8% 3/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Flatulence	18.8% 3/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Constipation	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Psychiatric disorders Abnormal dreams	12.5% 2/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Psychiatric disorders Insomnia	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Psychiatric disorders Nightmare	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Psychiatric disorders Restlessness	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
General disorders Chest discomfort	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
General disorders Fatigue	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
General disorders Vessel puncture site pain	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Skin and subcutaneous tissue disorders Skin irritation	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Eye disorders Blepharospasm	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Eye disorders Conjunctivitis allergic	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Eye disorders Eye pruritus	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Eye disorders Eyelid irritation	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Infections and infestations Cellulitis	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Infections and infestations Syphilis	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Injury, poisoning and procedural complications Arthropod bite	12.5% 2/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Neutropenia	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Cardiac disorders Palpitations	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.	6.2% 1/16 • Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months. Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo, Inc.

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place