A GBT021601 ADME Microtracer Study in Healthy Volunteers

A PHASE 1 STUDY TO ASSESS THE MASS BALANCE, EXCRETION, AND PHARMACOKINETICS OF [14C]-GBT021601, AN ORAL HEMOGLOBIN SPOLYMERIZATION INHIBITOR, IN HEALTHY PARTICIPANTS

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: GBT021601

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728
    • ICON Early Phase Clinic, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; open-label GBT021601	Drug: GBT021601; Single oral dose of 200 mg GBT021601, containing ~74 kBq (~2 µCi) of [14C]-GBT021601

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Data reported in microgram equivalent per milliliter (mcgEq/mL).	Predose (within 60 minutes prior to 14C-GBT021601 dosing)
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	Data are reported as aggregate of all scheduled time points.	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
Cumulative Fraction of [14C]-GBT021601 Total Radioactivity Excreted in Urine and Feces	Data are reported as aggregate of all scheduled time points.	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
Area Under the Plasma Concentration-Time Curve From Time Zero (0) to 24 Hours (AUC0-24) of GBT021601 in Whole Blood and Plasma	Area under the plasma concentration-time curve up to 24 hours post dose. Data reported in Hour*microgram/millimeter (h*mcg/mL).	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 From Time Zero (0) to 24 Hours (AUC0-24) of 14C-GBT021601 in Whole Blood and Plasma	Area under the plasma concentration-time curve up to 24 hours postdose. Data reported in hour*microgram equivalent/milliliter (h*mcgEq/mL).	Day 1 (prior to dosing) at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours
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	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.	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 14C-GBT021601 in Whole Blood and Plasma	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.	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 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	Apparent terminal elimination half-life, calculated as 0.693/kel where kel is Apparent terminal elimination rate constant.	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 14C-GBT021601 in Whole Blood and Plasma	Apparent terminal elimination half-life, calculated as 0.693/kel where kel is Apparent terminal elimination rate constant.	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 (CLR) of GBT021601 and 14C-GBT021601 in Urine	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.	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 (Vz/F) of GBT021601 in Whole Blood and Plasma	Apparent volume of distribution at terminal phase, calculated as: (CL/F) Apparent total clearance, calculated as dose/AUC0-inf/Kel.	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 (Vz/F) of 14C-GBT021601 in Whole Blood and Plasma	Apparent volume of distribution at terminal phase, calculated as: (CL/F) Apparent total clearance, calculated as dose/AUC0-inf/Kel.	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 (CL/F) of GBT021601 in Whole Blood and Plasma	Apparent total clearance, calculated as dose/AUC0-inf.	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 (CL/F) of 14C-GBT021601 in Whole Blood and Plasma	Apparent total clearance, calculated as dose/AUC0-inf.	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 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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).	From Day 1 up to maximum of Day 57
Number of Participants With Clinically Significant Laboratory Values	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.	Day 1 of dosing to Day 207
Number of Participants With Clinically Significant Vital Signs Values	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.	Day 1 of dosing to Day 207
Number of Participants With Clinically Significant ECG Values	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.	Day 1
Number of Participants With Clinically Significant Physical Examination Values	Physical Examination test included body weight and height. physical examination was conducted at screening. Clinical significance was judged by investigator.	Screening (-28 Day to -2 Day, day with respect to dosing)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): August 10, 2023
• Study Completion (Actual): August 10, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT021601-013; C5351003 (Other Identifier: Alias Study Number); 2022-003108-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No