A GBT021601 ADME Microtracer Study in Healthy Volunteers

Phase 1

Completed

Conditions: Sickle Cell Disease

Interventions: Drug: GBT021601

Registration Number: NCT05718687

Lead Sponsor: Pfizer

Brief Summary: An Open-label Study of GBT021601 in 8 to 10 healthy male or female participants to evaluate the absorption, distribution, metabolism, and excretion (ADME) of GBT021601.

Detailed Description: This is an open-label Study administering GBT021601 as a single oral dose of 200 mg in healthy participants.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Body mass index (BMI): 18.0 to 27.0 kg/m2, inclusive, at screening.
Body weight ≥ 50 kg at screening
Females must be nonlactating and nonpregnant (as confirmed by a negative serum pregnancy test at screening and admission for all females), or of nonchildbearing potential (ie, either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year postmenopausal [defined as at least 12 months no menses, and confirmed by a follicle-stimulating hormone test, at screening]).
Creatinine clearance (glomerular filtration rate) as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula: ≥90 mL/min, at screening.

Exclusion Criteria

History or presence of conditions which, in the opinion of the Investigator, are known to interfere with the ADME of drugs, such as previous surgery on the gastrointestinal tract (including removal of parts of the stomach, bowel, liver, gall bladder, or pancreas). Participants who have a history of appendectomy are eligible for enrollment.
History of chronic constipation, or recent complaints of an irregular defecation
Significant and/or acute illness at screening or within 5 days prior to study drug administration that may impact safety assessments, in the opinion of the Investigator.
Known personal or family history of congenital long QT syndrome or known family history of sudden death.
Participation in another ADME study with a radiation burden >0.1 mSv in the period of 1 year prior to screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	GBT021601	open-label GBT021601

Primary Outcome Measures

Name	Time	Method
GBT021601 Concentration in Whole Blood and Plasma at Predose	Predose (within 60 minutes prior to GBT021601 dosing)
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at Predose	Predose (within 60 minutes prior to 14C-GBT021601 dosing)	Data reported in microgram equivalent per milliliter (mcgEq/mL).
GBT021601 Concentration in Whole Blood and Plasma at 0.25 Hours	0.25 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentrations in Whole Blood and Plasma at 0.25 Hours	0.25 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 0.50 Hours	0.50 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 0.50 Hours	0.50 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 1 Hours	1 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 6 Hours	6 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 8 Hours	8 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 8 Hours	8 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 12 Hours	12 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 12 Hours	12 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 24 Hours	24 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 24 Hours	24 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 48 Hours	48 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 48 Hours	48 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 72 Hours	72 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 1 Hours	1 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 2 Hours	2 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 2 Hours	2 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 3 Hours	3 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 3 Hours	3 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 4 Hours	4 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 4 Hours	4 hours post dosing on Day 1
GBT021601 Concentration in Whole Blood and Plasma at 6 Hours	6 hours post dosing on Day 1
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 72 Hours	72 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 96 Hours	96 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 96 Hours	96 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 144 Hours	144 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 144 Hours	144 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 168 Hours	168 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 168 Hours	168 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 312 Hours	312 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 312 Hours	312 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 480 Hours	480 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 480 Hours	480 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 648 Hours	648 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 648 Hours	648 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 816 Hours	816 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 816 Hours	816 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 984 Hours	984 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 984 Hours	984 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 1320 Hours	1320 hours post dosing
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 264 Hours	264 hours post dose
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 1320 Hours	1320 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 1656 Hours	1656 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 1656 Hours	1656 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 1992 Hours	1992 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 1992 Hours	1992 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 2328 Hours	2328 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 2328 Hours	2328 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 2664 Hours	2664 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 2664 Hours	2664 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 3240 Hours	3240 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 3240 Hours	3240 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 3576 Hours	3576 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 3576 Hours	3576 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 4248 Hours	4248 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 4248 Hours	4248 hours post dosing
GBT021601 Concentration in Whole Blood and Plasma at 4920 Hours	4920 hours post dosing
14C-GBT021601 Total Radioactivity Concentration in Whole Blood and Plasma at 4920 Hours	4920 hours post dosing
Cumulative Amount of [14C]-GBT021601 Total Radioactivity Excreted in Urine and Feces	Day 1 (prior to dosing), after dosing from 0-6 hours, 6-12 hrs, 12-24 hrs postdose for urine, 24-hr intervals up to Day 29; 816 hrs , 984 hrs, 1320 hrs, 1656 hrs, 1992 hrs, 2328 hrs, 2664 hrs, 3240 hrs, 3576 hrs, 4248 hrs, and 4920 hrs post-dose	Data are reported as aggregate of all scheduled time points.
Cumulative Fraction of [14C]-GBT021601 Total Radioactivity Excreted in Urine and Feces	Day 1 (prior to dosing), after dosing from 0-6 hours, 6-12 hrs, 12-24 hrs postdose for urine, 24-hr intervals up to Day 29; 816 hrs , 984 hrs, 1320 hrs, 1656 hrs, 1992 hrs, 2328 hrs, 2664 hrs, 3240 hrs, 3576 hrs, 4248 hrs, and 4920 hrs post-dose	Data are reported as aggregate of all scheduled time points.
Area Under the Plasma Concentration-Time Curve From Time Zero (0) to 24 Hours (AUC0-24) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing) at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours	Area under the plasma concentration-time curve up to 24 hours post dose. Data reported in Hour\microgram/millimeter (h\mcg/mL).
Area Under the Plasma Concentration-Time Curve From Time Zero (0) to 24 Hours (AUC0-24) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing) at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours	Area under the plasma concentration-time curve up to 24 hours postdose. Data reported in hour\microgram equivalent/milliliter (h\mcgEq/mL).
Area Under the Concentration-Time From Time Zero to the Last Measurable Concentration (AUC0-last) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Area Under the Concentration-Time From Time Zero to the Last Measurable Concentration (AUC0-last) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Area under the plasma concentration-time curve from time 0 to infinity calculated as: AUC0-inf=AUC0-t+Clast/kel, where Clast is the last measurable plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Area under the plasma concentration-time curve from time 0 to infinity calculated as: AUC0-inf=AUC0-t+Clast/kel, where Clast is the last measurable plasma concentration and Kel is apparent terminal elimination rate constant.
Maximum Observed Concentration (Cmax) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Maximum Observed Concentration (Cmax) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Time to Attain Maximum Observed Concentration (Tmax) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Time to Attain Maximum Observed Concentration (Tmax) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 288 Hours	288 hours post dose
Apparent Terminal Elimination Half-Life (t1/2) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent terminal elimination half-life, calculated as 0.693/kel where kel is Apparent terminal elimination rate constant.
Apparent Terminal Elimination Half-Life (t1/2) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent terminal elimination half-life, calculated as 0.693/kel where kel is Apparent terminal elimination rate constant.
Renal Clearance (CLR) of GBT021601 and 14C-GBT021601 in Urine	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Renal clearance was calculated as CLR = Ae0-inf/AUC0-inf. Where Ae indicates Cumulative amount of drug excreted and AUC0-inf indicates Area under the plasma concentration-time curve from time 0 to infinity.
Apparent Volume of Distribution at Terminal Phase (Vz/F) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent volume of distribution at terminal phase, calculated as: (CL/F) Apparent total clearance, calculated as dose/AUC0-inf/Kel.
Apparent Volume of Distribution at Terminal Phase (Vz/F) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent volume of distribution at terminal phase, calculated as: (CL/F) Apparent total clearance, calculated as dose/AUC0-inf/Kel.
Apparent Total Clearance (CL/F) of GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent total clearance, calculated as dose/AUC0-inf.
Apparent Total Clearance (CL/F) of 14C-GBT021601 in Whole Blood and Plasma	Day 1 (prior to dosing), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144,168, 312, 480, 648, 816, 984,1320,1656,1992, 2328, 2664, 3240, 3576, 4248 and 4920 hours post-dose	Apparent total clearance, calculated as dose/AUC0-inf.
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 0-6 Hours	0-6 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 6-12 Hours	6-12 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 12-24 Hours	12-24 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 0-24 Hours	0-24 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 24 Hours	24 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 48 Hours	48 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 72 Hours	72 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 96 Hours	96 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 120 Hours	120 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 144 Hours	144 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 168 Hours	168 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 192 Hours	192 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 216 Hours	216 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 240 Hours	240 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 312 Hours	312 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 336 Hours	336 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 360 Hours	360 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 384 Hours	384 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 408 Hours	408 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 432 Hours	432 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 456 Hours	456 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 480 Hours	480 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 504 Hours	504 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 528 Hours	528 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 552 Hours	552 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 576 Hours	576 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 600 Hours	600 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 624 Hours	624 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 648 Hours	648 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 816 Hours	816 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 984 Hours	984 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 1320 Hours	1320 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 1656 Hours	1656 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 1992 Hours	1992 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 2328 Hours	2328 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 2664 Hours	2664 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 3240 Hours	3240 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 3576 Hours	3576 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 4248 Hours	4248 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 4920 Hours	4920 hours post dose

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From Day 1 up to maximum of Day 57	An Adverse event (AE) was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. TEAEs were those which occurred (or worsened) after the dose of study drug during the on-treatment period, defined as the period after the dose of study drug and through the minimum of (Study Day 57, study discontinuation).
Number of Participants With Clinically Significant Laboratory Values	Day 1 of dosing to Day 207	Blood and urine samples was collected for clinical laboratory assessments. Clinical Laboratory Values included Clinical chemistry: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin (total, direct, and indirect), blood urea nitrogen, calcium, chloride, creatinine, gamma glutamyl transferase, glucose, lactate dehydrogenase, magnesium, phosphorus, potassium, sodium, total protein, and uric acid. Hematology: leukocytes, erythrocytes, hematocrit, Hb, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count (ie, thrombocytes), RBC count, and white blood cell count etc. Urinalysis: determination of pH and specific gravity, and presence of bilirubin, blood, glucose, ketones, nitrite, protein, leukocytes, and urobilinogen etc. Coagulation, Serology, Drug and alcohol screen and Pregnancy test. Clinical significance was judged by investigator.
Number of Participants With Clinically Significant Vital Signs Values	Day 1 of dosing to Day 207	Systolic and diastolic blood pressure and pulse was recorded after the participant had rested for at least 5 minutes in the supine position. Body temperature and respiratory rate was also measured. Clinical significance was judged by investigator.
Number of Participants With Clinically Significant ECG Values	Day 1	Standard 12-lead ECGs were performed after the participant had rested quietly for more than 5 minutes in a supine position utilizing an ECG machine that was equipped with computer-based interval measurements. The following measurement was recorded: the heart rate (of \<45 or \>100 beats per minute (BPM) , PR interval, QT interval, QT interval corrected using Fridericia's formula (QTcF) of \>450 msec for males and \>470 msec for females, and QRS duration. Any cardiac rhythm other than sinus rhythm that was interpreted by the Investigator was clinically significant.
Number of Participants With Clinically Significant Physical Examination Values	Screening (-28 Day to -2 Day, day with respect to dosing)	Physical Examination test included body weight and height. physical examination was conducted at screening. Clinical significance was judged by investigator.