A PHASE 1 STUDY TO ASSESS THE MASS BALANCE, EXCRETION, AND PHARMACOKINETICS OF [14C]-GBT021601, AN ORAL HEMOGLOBIN SPOLYMERIZATION INHIBITOR, IN HEALTHY PARTICIPANTS
Phase: PHASE1
Conditions: Sickle Cell Disease
Sponsor: Pfizer



CLINICAL STUDY PROTOCOL
GBT021601-013 / GBT2180A-2180AX 
VERSION 3.0 – 13 MAR 2023
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Table 1      Schedule of Assessments 
 
 
Study Days
Assessments 
Screening
(-28 to -2)
Long-term Confinement in CRU (Days -1 to 29) a 
24-hour Visits a, b 
-1
1
2
3
4
5
6
7
8
14 21 28 29 35
42 56 70 84 98 112 136 150 178 206-207
-36 -43 -57 -71 -85 -99 -113 -137 -151 -179 [EoS/ET]
Long-term confinement 
X-----------------------------------------------------------------X 
Confinement for 24 hours a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X
X
X
X
X 
X 
X 
X 
X 
Window for 24-hour visits 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
±1 day 
±2 days 
Informed consent
X
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical history 
X 
X c  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height/body weight/BMI d 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs e 
X 
 
X 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
X  
 
 
 
 
X b 
12-lead ECGs f 
X 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination g 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X b 
Pregnancy test (females only) h 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
X  
X  
X 
X b 
FSH test (females only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical safety laboratory i 
X 
X  
 
 
 
 
 
X  
 
 
X  
 
 
 
 
X  
 
 
 
 
X b 
Coagulation panel (PT, aPTT, INR) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Creatinine clearance j 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (hepatitis A/B/C, HIV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 testing (PCR) 
 
X  
X  
 
 
 
 
 
 
 
 
 
Xr 
Xr 
Xr Xr
Xr
Xr 
Xr 
Xr 
Xr 
Xr 
X b, r 
Drug and alcohol screening 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
X------------------at indication only--------------------X b 
Study drug administration 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for PK of 
GBT021601 and total radioactivity l 
 
 
X 
X
X
X
X  
X
X
X
X
X  
X 
X 
X
X
X
X
X 
X 
X 
X 
X 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for metabolite 
identification n 
 
 
X 
X
X
X
X
X
X
X
X
X
X  
 
 
 
 
X
X
X 
X 
X 
X 
X 
Collection of urine o 
 
 
X 
X
24-hour collection intervals 
X 
X 
X
X
X
X
X 
X 
X 
X 
X 
Collection of feces p 
 
X 
24-hour collection intervals 
X 
X 
X
X
X
X
X 
X 
X 
X 
X 
Collection of vomitus, if produced q 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous/concomitant medication 
X 
X 
X---------------------------------------------------------------------------------------------------------------------------- X b 
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CLINICAL STUDY PROTOCOL
GBT021601-013 / GBT2180A-2180AX 
VERSION 3.0 – 13 MAR 2023
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Adverse events 
X 
X 
X---------------------------------------------------------------------------------------------------------------------------- X b 
Abbreviations:  aPTT=activated  partial  thromboplastin  time;  BMI=body  mass  index;  COVID-19=coronavirus  disease  2019;  CRU=clinical  research  unit; 
ECG=electrocardiogram; EoS=end of study; ET=early termination; FSH=follicle-stimulating hormone; HIV=human immunodeficiency virus; INR=international 
normalized ratio; PCR=polymerase chain reaction; PK=pharmacokinetic(s); PT=prothrombin time 
a.   Participants will be confined in the CRU from Day -1 to 29. Thereafter, participants will return to the CRU for up to 11 visits of 24 hours each to collect whole 
blood, plasma, urine, and feces. Criteria for ending the collection of blood and excreta in a participant after Day 29 are: 1) ≥90% of the administered radioactive 
dose is recovered in excreta collected to date, or 2) radioactivity is undetectable in urine and feces during 2 consecutive a 24-hour collection periods, or 
3) until the last visit on Day 206. 
b.   If the criteria for ending the collection of blood and excreta are met after Day 29 and before Day 206, participants will return to the CRU at a separate visit 
7 (±3) days after the last 24-hour visit to perform the EoS assessments as indicated with a ‘b’ in the column for Day 206/207 (EoS/ET). 
c.   Any updates to medical and surgical history will be recorded. 
d.   Height will be performed at screening only. BMI will be calculated using the height obtained at screening. 
e.   Vital signs (heart rate, blood pressure, respiratory rate, and body temperature) will be measured after a participant has rested at least 5 minutes in the supine 
position. Vital signs will be measured at screening, predose on Day 1, and at 1, 2, 8, 12, and 24 hours postdose, and on Days 35, 84, and 206 (EoS/ET). 
f.    12-lead ECGs will be recorded after a participant has rested at least 5 minutes in the supine position. Triplicate ECGs will be recorded at screening only; 
thereafter, standard single 12-lead ECGs will be taken on Day -1 and on Day 1 at predose and at 1 and 2 hours postdose. 
g.   A complete physical examination will be conducted at screening. Targeted physical examinations will be conducted at the other time points. Symptom-directed 
physical examinations may also be conducted at any time, per the Investigator’s discretion. 
h.   For females only: serum pregnancy test is required at screening only; urine pregnancy test at all other visits, with serum confirmation if positive. 
i.    Clinical safety laboratory (including hematology, serum chemistry, and urinalysis) will be obtained at screening and on Days -1, 7, 28, 84, and 206 (EoS/ET). 
j.     Creatinine clearance (CLcr) will be calculated at screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. 
   
. 
l. 
Whole blood and plasma samples for PK of GBT021601 and total radioactivity will be taken at predose (within 60 minutes prior to GBT021601 dosing), and 
at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 144 (Day 7), 168 (Day 8), 312 (Day 14), 480 (Day 21), and 648 hours 
(Day 28) postdose. Additional samples will be obtained on Days 35, 42, 56, 70, 84, 98, 112, 136, 150, 178, and 206 (depending on if criteria for ending 
collection of urine and feces are met [see Footnote a], collection of samples may be ended prior to Day 206). Collections up to and including the 8 hours 
postdose sample will be collected after a participant has rested at least 5 minutes in the supine position. 
 
 
 n.    
Whole blood and plasma samples for metabolite identification will be collected at predose and 1, 2, 8, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 
120 (Day 6), 144 (Day 7), 168 (Day 8), 312 (Day 14), 480 (Day 21), and 648 hours (Day 28) hours postdose. Collections up to and including the 8 hours 
postdose sample will be collected after a participant has rested at least 5 minutes in the supine position.  Whole blood and plasma samples for metabolite 
identification will also be collected at the visits on Days 84 (1992 hours postdose), 98 (2328 hours), 112 (2664 hours), 136 (3240 hours), 150 (3576 hours), 
178 (4248 hours), and 206 (4920 hours; EoS/ET).
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CLINICAL STUDY PROTOCOL
GBT021601-013 / GBT2180A-2180AX 
VERSION 3.0 – 13 MAR 2023
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Confidential
 
 
 
 
o.   Urine samples for PK of GBT021601 and total radioactivity will be collected on Day 1 (prior to dosing) and after dosing from 0 to 6 hours, 6 to 12 hours, 12 to 
24 hours postdose, and thereafter in 24-hour intervals up to Day 29. Urine will also be collected in 24-hour intervals starting on Days 35 (816 hours postdose), 
42 (984 hours), 56 (1320 hours), 70 (1656 hours), 84 (1992 hours), 98 (2328 hours), 112 (2664 hours), 136 (3240 hours), 150 (3576 hours), 178 (4248 hours), 
and 206 (4920 hours) in accordance with the applicable time windows (depending on if criteria for ending collection of blood and excreta are met [see 
Footnote a], the collection may be ended prior to Day 206). Selected pooled urine will be used for metabolite identification. 
p.   Fecal collections for the analysis of total radioactivity will be made at predose on Day -1, and complete collections will be made after dosing in 24-hour 
intervals up to Day 29. Feces will also be collected in 24-hour intervals starting on Days 35 (816 hours postdose), 42 (984 hours), 56 (1320 hours), 
70 (1656 hours), 84 (1992 hours), 98 (2328 hours), 112 (2664 hours), 136 (3240 hours), 150 (3576 hours), 178 (4248 hours), and 206 (4920 hours) in 
accordance with the applicable time windows (depending on if criteria for ending collection of blood and excreta are met [see Footnote a], the collection may 
be ended prior to Day 206). Participants will receive the appropriate containers to collect all feces at home within 24 hours prior to admission on Day -1 and 
each of the 24-hour stays. These fecal samples will be used if no feces is produced between admission on Day -1 and study drug administration (as a blank 
sample) or during the 24-hour stays after Day 29, respectively. Selected pooled fecal samples will be used for metabolite identification. 
q.   Collection of vomitus for analysis of total radioactivity concentrations (if possible), if produced between dosing and 24 hours postdose. 
r.    COVID-19 testing may be performed at the Inv es ti gator ’s  dis c r eti on.