Clinical trial NCT05718687
Conditions: Sickle Cell Disease
Sponsor: Pfizer
Start date: 2022-12-22; Completion date: 2023-08-10
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: open-label GBT021601
Interventions: intervention 1: GBT021601
Intervention descriptions: intervention 1: Single oral dose of 200 mg GBT021601, containing \~74 kBq (\~2 µCi) of \[14C\]-GBT021601

Protocol documents:
Prot_000.pdf: 














CLINICAL STUDY PROTOCOL
GBT021601-013 / GBT2180A-2180AX 
VERSION 3.0 – 13 MAR 2023
Page 11 of 59
Confidential
 
 
 
 
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
Page 12 of 59
Confidential
 
 
 
 
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
Page 13 of 59
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. 





























































































SAP_001.pdf: 




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Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 4 of 30 
3.0 Introduction 
This Statistical Analysis Plan (SAP) describes the statistical methods that will be used during the analysis 
and reporting of data collected under Global Blood Therapeutics (GBT), Inc., Protocol GBT021601-013. 
This SAP should be read in conjunction with the clinical study protocol and electronic case report form 
(eCRF). This version of the plan has been developed using the protocol Version 3.0, dated 13-Mar-2023 
(including all amendments up to this protocol date) and the final eCRF(s) dated 31-Oct-2022. 
An approved and signed SAP is a requirement for database lock.  
This SAP only covers the results that will be processed by the ICON Early Development Services (EDS) 
Biostatistics Department, Statistical Programming Department and Pharmacokinetic Department. 
ICON EDS will perform the pharmacokinetic (PK), and safety and tolerability evaluation.  
Metabolic profiling is not described in this SAP and will not be included in the corresponding TFLs. 
This SAP supersedes the statistical considerations identified in the protocol; where considerations are 
substantially different, they will be so identified. Any post-hoc or unplanned analyses, or significant changes 
from the planned analysis in this SAP performed to provide results for inclusion in the clinical study report 
(CSR) but not included in this SAP, will be clearly identified in Section 9.8.2 of the CSR. Changes to planned 
analyses do not require an updated SAP but should be included in the CSR if significant. 
4.0 Changes from Previous Version of Approved SAP 
This is the first version of the SAP. 
5.0 Study Objectives 
5.1 Primary 
• 
To determine the whole blood and plasma concentrations of 14C-GBT021601 total radioactivity. 
• 
To assess the mass balance by determining 14C-GBT021601 total radioactivity excreted in urine 
and feces. 
• 
To determine the PK of GBT021601 in whole blood, plasma, and urine. 
5.1.1 Primary Endpoint 
• 
Concentrations of GBT021601 and of 14C-GBT021601 total radioactivity in whole blood and plasma  
• 
Amount and fraction of 14C-GBT021601 total radioactivity dose excreted in urine, feces, emesis (if 
produced). 
• 
PK parameters of GBT021601 and 14C-GBT021601 total radioactivity, as feasible, in whole blood 
and plasma (AUC0-24, AUC0-last, AUC0-inf, Cmax, Tmax, T1/2, CLR, CL/F, and Vz/F, if possible, and any 
other PK parameters as appropriate). 
• 
Distribution of 14C- GBT021601 total radioactivity in urine and feces.  
5.2 Secondary 
• 
To assess the safety and tolerability of GBT021601 administration in healthy participants. 
• 
To characterize and identify metabolites of 14C-GBT021601 in whole blood, plasma, urine, and 
feces. 
5.2.1 Secondary Endpoint 
• 
Incidence and severity of adverse events (AEs).  
• 
Other safety results: clinical laboratory results, vital signs, 12-lead electrocardiogram (ECG) and 
physical examinations.  




Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 6 of 30 
Visit 
Screening 
Long-term confinement in CRU 
24-hour visits (up to 11 visits) a 
Activity 
Eligibility 
Admission 
Dosing 
Assessments/ 
PK sampling 
PK sampling  
(collection of blood and excreta) 
Study Day(s) -28 to -2 
Day -1 
Day 1 
Days 1 to 29 (ie, 
discharge) 
35-36 (±1 day),  
42-43 (±1 day),  
56-57(±2 days),  
70-71 (±2 days),  
84-85 (±2 days), 
98-99 (±2 days),  
112-113 (±2 days), 
136-137 (±2 days), 
150-151 (±2 days), 
178-179 (±2 days), 
206-207 (±2 days; EoS/ET)  
CRU=clinical research unit; EoS=end of study; PK=pharmacokinetic(s) 
a. 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 24-hour collection periods, or 3) until the EoS 
visit on Day 206. If these criteria are met after Day 29 and before Day 206, participants will return to the 
CRU for EoS assessments at a separate visit 7 (±3) days after the last 24-hour visit. 
 
6.1 Sample Size Considerations 
 No formal sample size calculation was made. Based on similar studies, the sample size of 8 – 10 
participants was considered appropriate for this Phase 1 ADME study. 
7.0 Overview of Planned Analysis 
7.1 Changes from Protocol 
The % Hb occupancy (at Cmax) was added as a PK parameter.  
The protocol states “Concentrations of total radioactivity in blood and excreta will be assayed weekly during 
the 30-day confinement phase and thereafter within 3 days of the 24-hour collections.”  However, blood 
and plasma will not be assayed weekly for concentrations of total radioactivity during the 30-day 
confinement phase. Only excreta will be assayed weekly for total radioactivity during the 30-day 
confinement phase, as described in the Protocol Clarification Memo dated 27-Oct-2022. 
The definition of treatment emergent adverse events (TEAEs) has been updated compared to the protocol. 
TEAE are those which occur (or worsen) after the dose of study drug, consistent with the protocol text. 
Additionally, AEs need to take place during the on-treatment period, defined as the period after the dose of 
study drug and before the minimum of (Study Day 56, study discontinuation), to be considered as TEAEs. 
Day 56 has been chosen for this purpose based on the half-life of GBT021601.  
7.2 Planned interim Analysis and Key Results 
There are no interim analyses planned for this study. 
7.3 Final Analysis 
 The final TFLs will be created after all participants have completed the end of study (EOS) visit or have 
discontinued the study. 
 


Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 7 of 30 
8.0 Data Review 
8.1 Data Management 
Data handling and transfer will take place under the ICON Data Management Plan for the study. 
8.2 Acceptance of Data for Summarization 
Programming of analysis datasets and TFLs may be ongoing during the data management of the study. 
However, programming of analysis datasets and TFLs will be completed and quality controlled (QC’d) after 
database lock. The draft safety TFLs will also be QC’d before database lock. Only quality assured (QA’d) 
results released by the Safety Laboratory, Bioanalytical Laboratory, or other external data source will be 
used for the programming of analysis datasets and TFLs for the final report. Any data values requiring 
investigation or corrections that are identified while programming the analysis datasets and TFLs will be 
sent to the project Data Manager for resolution. If the issue affects the TFLs the Programmer or Statistician 
who identified the issue will follow it to resolution. 
9.0 Definitions and General Analysis Methods 
9.1 Analysis Data Presentation 
9.1.1 Rounding 
In listings, data will be presented with the same precision as the original data. Derived data will be rounded 
for presentation purposes.  
For all summaries, the mean and median will be presented to one decimal place greater than the data, 
standard deviation to 2 greater than the data, and the minimum (min) and maximum (max) will be presented 
to the same number of decimal places as the data. Frequency percentages will be presented with one 
decimal. Individual values and descriptive statistics of PK concentrations in all matrices (e.g. whole blood, 
plasma) and parameters will generally be presented with 3 decimals, except tmax (which will be reported 
with 2 decimals). Values greater than 999 will be presented as integers. The coefficients of variation (CVs) 
as a percentage will be presented to 1 decimal place. 
9.1.2 Imputation 
Unless otherwise noted, data will not be imputed. Imputation will only be used for: 
• 
PK concentrations below the quantifiable limit (BQL) (see Section 16.1.2). 
• 
PK amounts excreted will be interpolated between confinement and 24 hour visits and between 
subsequent 24 hour visits (see Section 16.1.2) 
• 
Missing start or end date/times of AEs for the calculation of onset and duration (see Section 17.1.1). 
• 
Missing adverse event (AE) severity, relationship and seriousness of AEs see Section 17.1.1 ). 
• 
Safety laboratory data that are <x or >x (e.g. “<1.03”, “>1000”): the analysis value or normal limit value 
will be the value of the detection limit itself plus or minus one precision unit for the parameter concerned 
(respectively 1.02 and 1001 in the example). The values before imputation (“<1.03”, “>1000”) will only 
be shown in listings. Listings will present the values before imputation. 
9.1.3 Descriptive Statistics 
Unless otherwise indicated, continuous variables will be summarized with the following descriptive 
statistics: n (number of observations), (arithmetic) mean, standard deviation (SD), min value, median, and 
max value. For the summary statistics for PK, see Section 16.2.1 for PK concentrations and Section 16.2.3 
for PK parameters. 








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Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 15 of 30 
16.1.2 Urine, Feces and Vomitus (if applicable) Variables 
16.1.2.1 Concentrations 
• 
GBT021601 concentrations and amounts excreted in urine and feces 
• 
14C-GBT021601 Total Radioactivity, concentrations and amounts excreted in urine 
• 
14C-GBT021601 Total Radioactivity, concentrations and amounts excreted in feces 
• 
14C-GBT021601 Total Radioactivity, concentrations and amounts excreted in vomitus, if applicable. 
 
16.1.2.2 Pharmacokinetic Amounts Excreted 
Urinary and fecal PK parameters will be calculated using SAS and/or WNL. Excretions in mg equivalent 
(mg eq) for each interval (Aet1-t2) will be derived from the urinary and fecal concentrations and the sample 
collection interval volumes or weights respectively, by multiplying the concentration in the interval (C) and 
the volume or weight (V): 
 
𝐴𝐴𝐴𝐴𝑡𝑡1−𝑡𝑡2 = 𝐶𝐶 × 𝑉𝑉 
If the concentration is < lower limit of quantification (LLOQ), the excretion will be assumed to be zero. For 
intervals in which no sample was collected (e.g., no defecation), the excretion will be assumed to be zero.  
Cumulative excretions for each continuously sampled interval will be calculated by adding the excretions in 
the current and all previous collection intervals: 
 
𝐴𝐴𝐴𝐴0−𝑡𝑡= ෍൫𝐴𝐴𝐴𝐴𝑡𝑡𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠−𝑡𝑡𝑒𝑒𝑒𝑒𝑒𝑒൯𝑖𝑖
𝑛𝑛
𝑖𝑖=1
 
The excretion rate ( ∆𝐴𝐴𝐴𝐴/∆𝑡𝑡) will also be calculated by dividing the excretion in each interval by the time 
difference in hours between the end and the start of the collection interval: 
 
∆𝐴𝐴𝐴𝐴
∆𝑡𝑡= 
𝐴𝐴𝐴𝐴
𝑡𝑡𝑒𝑒𝑒𝑒𝑒𝑒− 𝑡𝑡𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠
 
 
If a participant has not met the criteria for ending the collection of blood and excreta on Day 29 (i.e., end of 
confinement), cumulative excretion will be calculated up to and including the last continuous 24 hour visit 
during confinement. Interpolation will be used to estimate urinary and fecal excretion between confinement 
and 24 hour visits and between subsequent 24 hour visits, the midpoint method will be used to estimate  
Ae tstart-tend. The excretion rate of each collection interval will be plotted as a function of the midpoint of the 
respective interval. The area under this curve is Ae. 
16.1.2.3 Excretion Parameters 
• 
PK Parameters for GBT021601 and 14C-GBT021601 total radioactivity as defined in Table 5.  
 




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Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 18 of 30 
The arithmetic mean values of the cumulative amount excreted in % of the dose in urine, feces and total 
(urine + feces) versus time (last time point of the interval) will be presented. 
 
Individual plots showing the cumulative amount excreted in % of the dose for all participants versus time 
(last time point of the interval) in urine, feces and total will be presented.  
17.0 Safety Analyses  
17.1 Safety Variables 
The following safety variables will be summarized: 
• 
Adverse Events (AEs) 
• 
Vital Signs 
o 
Supine Blood Pressure  
 
Systolic Blood Pressure (SBP) 
 
Diastolic Blood Pressure (DBP) 
o 
Heart rate 
o 
Body temperature 
o 
Respiration rate 
• 
Electrocardiograms (ECG) 
o 
Heart Rate 
o 
PR Interval 
o 
QRS Duration 
o 
QT Interval 
o 
QTcF (Fridericia) Interval 
• 
Clinical Laboratory Evaluations 
o 
Clinical Chemistry  
o 
Hematology 
o 
Urinalysis 
o 
Coagulation 
• 
Physical Examination 
17.1.1 Adverse Events 
All AE summaries will include only treatment emergent adverse events (TEAEs). TEAE are those which 
occur (or worsen) after the dose of study drug during the on-treatment period, defined as the period after 
the dose of study drug and before the minimum of (Study Day 56, study discontinuation). Day 56 has been 
chosen for this purpose based on the half-life of GBT021601.  All AEs (including non-treatment-emergent 
events) recorded on the eCRF will be listed, where non-TEAEs will be flagged.  
A summary (overview) table with numbers, events and percentages of participants reporting TEAEs, TEAEs 
related to study drug (related/unrelated), TEAEs by severity (mild, moderate, severe, life-threatening, or 
death), serious AEs (SAEs), and participants who discontinued the study due to an AE will be provided. 
A breakdown of the number of TEAEs, number and percentage of participants reporting each TEAE, 
categorized by body system and preferred term coded according to MedDRA (Version 25.0), will be 
presented. Counting will be done by participant (participants will be counted once within each body system 
or preferred term) and by event.  
One such table will be presented for all TEAEs. Another table like this will be presented for TEAEs 
considered to be related to the study medication. TEAEs’ relationship to study drug is categorized as 
‘related’ or ‘not related’. 
 Lastly, one such table for all TEAES by severity (categories as recorded in the eCRF: Grade 1 mild, Grade 
2 moderate, Grade 3 severe, Grade 4 life-threatening, or Grade 5 death), will be provided.  
A listing of AEs leading to study discontinuation will be provided. 


Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 19 of 30 
The following missing data will be imputed as defined (will not be presented in listings): 
• 
Missing AE start and / or end times for the calculation of onset and duration will be assumed to be 
at 00:01 for a start time and 23:59 for end times 
• 
Missing AE severity or relationship will be assumed to be severe or related, respectively 
• 
Missing AE start date/times for the determination of treatment emergence will be assumed to occur 
during on-treatment period unless partial date/time documents the AE as happening prior to 
treatment 
17.1.2 Deaths and Serious Adverse Events 
A listing of deaths and a listing of all SAEs will be provided by participant. 
17.1.3 Laboratory Data 
Clinical laboratory data will be presented using units from the study data tabulation model (SDTM) 
Controlled Terminology. 
All laboratory data will be listed. A separate listing of out-of-range values will also be provided. Normal 
ranges will be used directly from the clinical laboratory. 
Clinical laboratory results outside the reference range will be flagged. In case the out of reference range 
values were considered clinically significant by the Investigator, this will also be indicated in the listings as 
well as in the AE listing. Comments with regard to the laboratory test results will be shown in a separate 
listing.  
 
Results of continuous parameters recorded as being below or above a detection limit (e.g. “<1.5”, “>800”) 
will be imputed in the calculation of descriptive statistics as the detection limit plus or minus one precision 
unit of the respective parameter (in the above example: 1.4 and 801). Listings will present the values before 
imputation. 
Descriptive statistics summarizing continuous laboratory results of clinical chemistry, hematology (observed 
and derived changes from baseline) and coagulation (observed) by scheduled time will be included.  
17.1.4 Vital Signs 
All vital signs parameters (including changes from baseline) will be listed by participant. Descriptive 
statistics will be provided to summarize vital signs (observed and changes from baseline) by scheduled 
time. 
17.1.5 Electrocardiograms 
The observed measurements for all ECG parameters and the corresponding abnormalities and 
physicians’ conclusions will be listed by participant. The means of triplicate measurements for continuous 
parameters (at screening only) and the change from baseline of the mean triplicate measurements at each 
scheduled timepoint will be listed by participant. 
Descriptive statistics will be provided to summarize mean ECG parameters (observed and changes from 
baseline) by scheduled time. 
17.1.6 Physical Examination 
Findings at the physical examination will be listed. 
18.0 References 
SAS Institute, Inc., SAS® Version 9.4 software, Cary, NC. 
Phoenix WinNonlin(R) version 8.1 (Certara USA, Inc. Princeton, NJ, USA) 


Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 20 of 30 
Clinical Study Protocol. A PHASE 1 STUDY TO ASSESS THE MASS BALANCE, EXCRETION, AND 
PHARMACOKINETICS OF [14C]-GBT021601, AN ORAL HEMOGLOBIN S POLYMERIZATION 
INHIBITOR, IN HEALTHY PARTICIPANTS. Version 3.0, Final, 13 Mar 2023. 








Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 24 of 30 
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 Investigator’s discretion. 
 
 










Statistical Analysis Plan 
GBT2180A-2180AX 
Protocol: GBT021601-013 
Version Date: 01-May-2023 
EDSREP 009 T 01 G 
Page 29 of 30 
Appendix 4: Shells for Post-Text Tables, Figures and Listings 
Shells are provided in a separate document.