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GBT021601

Phase 1

Sickle Cell Disease | Small molecule | Hematology |Pfizer, Inc.|Last Updated: Jan 8, 2025

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
Premium
Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
Premium
Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials3
Total Enrollment144
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05718687A GBT021601 ADME Microtracer Study in Healthy VolunteersPHASE1 COMPLETED 9Dec 22, 2022Aug 10, 2023Jan 8, 20251 Netherlands
NCT04983264A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)PHASE1 COMPLETED 6May 21, 2021Dec 6, 2022Jun 10, 20243 United States
NCT05036512A Study to Evaluate GBT021601 in Single and Multiple Doses in Healthy ParticipantsPHASE1 COMPLETED 129Dec 9, 2020Feb 7, 2023Jul 25, 20234 United States, Australia
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Study Endpoints
Primary Endpoints
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 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 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 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
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
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 264 Hours
264 hours post dose
Distribution of 14C- GBT021601 Total Radioactivity in Urine and Feces at 288 Hours
288 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
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
From first dose of study drug (Day 1) to at least 56 days after last dose of study drug (up to a maximum of 316 days)

An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A treatment-emergent AE (TEAE) was an AE that occurs or worsens during the on-treatment period defined as the time from the first dose of study drug through minimum of 56 days after last dose of study treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation if existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; was considered an important medical event. TEAEs and SAEs were reported for both Sickle Cell Disease (SCD) and non-SCD related events, in this outcome measure.

Number of Participants With Clinically Significant Physical Examination Findings
Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

Physical examination included were general appearance, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes, and nervous system. Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.

Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

Laboratory parameters included hematology(hemoglobin,hematocrit,red blood cell count,platelet count,white blood cell count,total neutrophils,eosinophils,monocytes,basophils,lymphocytes);blood chemistry(blood urea,nitrogen, creatinine,glucose,calcium,sodium,potassium,chloride,total bicarbonate,aspartate aminotransferase,alanine aminotransferase,total bilirubin,alkaline phosphatase,uric acid albumin,total protein);urinalysis(decimal logarithm of reciprocal of hydrogen ion activity \[pH\], glucose, protein, blood,ketones, microscopy\[urine tested positive for blood or protein\]),urine drug screening:cannabinoids,amphetamines,methamphetamines,opiates,methadone,cocaine,benzodiazepines,phencyclidine,barbiturates,alcohol breath test. Hemoximetry RBC deformability,dense cells test; erythropoietin,follicle stimulating hormone,pregnancy test,Serology panel for HIV 1/2 antibody,Hepatitis A, B and C,SARS CoV-2.Clinical significance of any parameter was determined at the investigator's discretion.

Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

Vital signs assessments included were systolic and diastolic blood pressure, heart rate, respiratory rate and body temperature. These measurements were taken after the participants had rested for at least 5 minutes in the supine position. Any clinically significant abnormal vital sign assessment required at least one repeat measurement. Clinical significance of any parameter was determined based on investigator's discretion.

Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

ECG values included here were Heart rate (HR), PR, QRS, QT, and QTcF intervals, interpretation of the tracings (eg, rhythm, presence of arrhythmia or conduction defects, any evidence of myocardial ischemia/infarction, or ST segment, T-wave, and U-wave abnormalities). Abnormal and clinically significant 12-lead ECG included QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 450 millisecond (ms), QRS interval \>= 120 ms, PR interval \> 220 ms, based on the average of triplicated ECG, assessed at Screening and Day-1. If any of these test results were out of range, then the test could be repeated once (in triplicate).

Safety, as assessed by frequency and severity of adverse events (AEs)
119 days from screening Part A, 134 days from screening Part B

AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized.

Safety, as assessed by changes in Heart Rate.
119 days from screening Part A, 134 days from screening Part B

Number of participants with changes in heart rate (bpm) as compared to baseline.

Safety, as assessed by changes in eGFR
119 days from screening Part A, 134 days from screening Part B

Number of participants with changes in eGFR from baseline

Safety, as assessed by changes in alanine aminotransferase (ALT)
119 days from screening Part A, 134 days from screening Part B

Number of participants with changes in alanine aminotransferase (ALT)

Safety, as assessed by changes in Blood pressure
119 days from screening Part A, 134 days from screening Part B

Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood

Plasma concentration
119 days from screening Part A

Time of Cmax

Secondary Endpoints
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
From Day 1 up to maximum of Day 57
Number of Participants With Clinically Significant Laboratory Values
Day 1 of dosing to Day 207
Number of Participants With Clinically Significant Vital Signs Values
Day 1 of dosing to Day 207
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeOTHER
Treatment Arms
ArmTypeDescription
TreatmentEXPERIMENTALopen-label GBT021601
Single-dose Period (Part A)EXPERIMENTALRefer to Study Description
Multiple Ascending-dose Period (Part B and Part C)EXPERIMENTALRefer to Study Description
PlaceboPLACEBO_COMPARATORPlacebo as a tablet or capsule with dose based off of preceding cohort's data.
GBT021601EXPERIMENTALGBT021601 as a tablet or capsule with dose based off of preceding cohort's data.
Interventions
NameTypeDescription
GBT021601DRUGSingle oral dose of 200 mg GBT021601, containing \~74 kBq (\~2 µCi) of \[14C\]-GBT021601
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Eligibility Criteria
Age Range18 Years — 55 Years
SexALL
Healthy VolunteersYes
Study Sites1

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 (...

Countries:NetherlandsUnited StatesAustralia
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