Sickle Cell Disease
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK), and pharmacodynamics (i.e., how the body absorbs, distributes, breaks down, and excretes) of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in participants with SCD, following single and multiple ascending doses.
Detailed description
This is an open-label intrapatient single dose followed by a multiple dose escalation study in at least six (6) participants with SCD.
Interventions
DRUGGBT021601
Tablets and capsules which contain GBT021601 drug substance
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female with SCD * Participants with SCD ages 18 to 60 years, inclusive. * Participant has provided documented informed consent. * Patients with stable and close to baseline hemoglobin value * Patients on HU should be on stable dose for at least 90 days prior to signing ICF
Exclusion criteria
* Patients had more than 10 VOC within 12 months of screening * Patients who are pregnant or nursing * Patients who receive RBC transfusion therapy regularly or received an RBC transfusion for any reason within 60 days of signing the ICF * Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF or within 24 days prior to Day 1 treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | Maximum observed concentration was defined as the peak concentration observed directly from the experimental data without any interpolation. The time to the maximum observed concentration was defined as the time corresponding to Cmax. |
| Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | AUC0-tau was defined from time 0 to time of the last quantifiable concentration and was calculated using the linear or logarithmic trapezoid rule. AUCtau was calculated by using hours\*microgram per milliliter (hr\*mcg)/mL. |
| Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | AUCinf was defined as the area calculated by linear/log trapezoid rule from time 0 to infinity with the area extrapolated from the last quantifiable concentration to infinity. |
| Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs post-dose on Day 1 | AUC0-24 was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. |
| Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | CL/F was a quantitative measure of the rate at which a drug substance was removed from the blood. It was calculated as dose of GBT021601 by AUC from time 0 to infinity. |
| Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | t1/2 was the time measured for the plasma concentration to decrease by one half. |
| Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was determined based on the fraction absorbed. |
| Percentage Hemoglobin Occupancy | Part A: Pre-dose,0.25,0.5,1,2,4, 6,8,12,24,36,48,72,168,336,504,672,1008 hrs on Day 1; Part B: Pre-dose,0.25 to 1,2 to 4 hrs post-dose on Day 56,63,70,77,84,91,98,105,112; Part C:Pre-dose on Day 1,14,28,42 and 0.25 to 1, 2 to 4 hrs post-dose on Day 28,42 | Percentage hemoglobin occupancy (%Hb Occupancy) refers to the proportion of hemoglobin molecules within red blood cells that were bound to study drug (GBT021601). Cmin and Cmax values was used to calculate %Hb occupancy: %Hb Occupancy = GBT021601\*RBC per Mean Corpuscular Hemoglobin Concentration (MCHC). |
| Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation. |
| Plasma Concentrations Versus Time Summary of GBT021601: Part B | Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218 | The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint. |
| Plasma Concentrations Versus Time Summary of GBT021601: Part C | Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98 | The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint. |
| Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time. |
| Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs, post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218 | The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time. |
| Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98 | The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time. |
| Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | The RBC concentration versus time summary was measured to identify quantity of RBC in a sample of blood over a specified duration. This analysis helped monitor RBC level over time. |
| Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218 | The RBC concentration versus time summary was measured to identify quantity of RBC in a sample of blood over a specified duration. This analysis helped monitor RBC level over time. |
| Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98 | The RBC concentration versus time summary involved tracking a quantity of RBC in a sample of blood over a specified duration. This analysis helped to monitor RBC level over time. |
| Plasma Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1 | The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint. |
| Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112 | Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation. |
| Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42 | Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation. |
| Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112 | Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation. |
| Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42 | Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All participants who received GBT021601 as single dose, multiple dose or extended treatment in Part A, Part B and Part C, respectively were included. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part B: Multiple Dose Period | Physician Decision | 0 | 1 | 0 |
| Part C: Extended Treatment Period | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 20.2 Years STANDARD_DEVIATION 2.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 1 / 6 | 2 / 6 | 1 / 4 | 5 / 6 | 5 / 6 | 3 / 4 |
| serious Total, serious adverse events | 0 / 6 | 2 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
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).
Time frame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
Population: Safety population was defined as all participants who received any amount of study drug (GBT021601).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Single Dose Period | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) | 1 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
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.
Time frame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
Population: Safety population was defined as all participants who received any amount of study drug (GBT021601).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Single Dose Period | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | 1 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
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.
Time frame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
Population: Safety population was defined as all participants who received any amount of study drug (GBT021601).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Single Dose Period | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Findings
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.
Time frame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
Population: Safety population was defined as all participants who received any amount of study drug (GBT021601).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Single Dose Period | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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)
Population: Safety population was defined as all participants who received any amount of study drug (GBT021601).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Single Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: SCD Related | 1 Participants |
| Part A: Single Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: SCD Related | 0 Participants |
| Part A: Single Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: Non-SCD Related | 5 Participants |
| Part A: Single Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: Non-SCD Related | 0 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: Non-SCD Related | 0 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: SCD Related | 3 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: Non-SCD Related | 5 Participants |
| Part B: Multiple Ascending- Dose Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: SCD Related | 2 Participants |
| Part C: Extended Treatment Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: Non-SCD Related | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs: SCD Related | 0 Participants |
| Part C: Extended Treatment Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: Non-SCD Related | 3 Participants |
| Part C: Extended Treatment Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs: SCD Related | 1 Participants |
Secondary
Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
CL/F was a quantitative measure of the rate at which a drug substance was removed from the blood. It was calculated as dose of GBT021601 by AUC from time 0 to infinity.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 1.39 Liter per hour | Geometric Coefficient of Variation 16.43 |
| Part A: Single Dose Period | Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 0.02 Liter per hour | Geometric Coefficient of Variation 29.55 |
| Part A: Single Dose Period | Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 0.004 Liter per hour | Geometric Coefficient of Variation 33.36 |
Secondary
Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was determined based on the fraction absorbed.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 480 Liter | Geometric Coefficient of Variation 13.3 |
| Part A: Single Dose Period | Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 6.87 Liter | Geometric Coefficient of Variation 22.56 |
| Part A: Single Dose Period | Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 1.61 Liter | Geometric Coefficient of Variation 26.23 |
Secondary
Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
AUC0-tau was defined from time 0 to time of the last quantifiable concentration and was calculated using the linear or logarithmic trapezoid rule. AUCtau was calculated by using hours\*microgram per milliliter (hr\*mcg)/mL.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 67.102 (hr*mcg)/mL | Geometric Coefficient of Variation 13.91 |
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 4597.8 (hr*mcg)/mL | Geometric Coefficient of Variation 27.07 |
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 19627.6 (hr*mcg)/mL | Geometric Coefficient of Variation 30.93 |
Secondary
Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
AUC0-24 was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 7.94 (hr*mcg)/mL | Geometric Coefficient of Variation 12.11 |
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 322.0 (hr*mcg)/mL | Geometric Coefficient of Variation 25.28 |
| Part A: Single Dose Period | Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 1363.3 (hr*mcg)/mL | Geometric Coefficient of Variation 29.9 |
Secondary
Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
AUCinf was defined as the area calculated by linear/log trapezoid rule from time 0 to infinity with the area extrapolated from the last quantifiable concentration to infinity.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 72.03 (hr*mcg)/mL | Geometric Coefficient of Variation 16.43 |
| Part A: Single Dose Period | Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 4914.50 (hr*mcg)/mL | Geometric Coefficient of Variation 29.55 |
| Part A: Single Dose Period | Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 234.08 (hr*mcg)/mL | Geometric Coefficient of Variation 13.95 |
Secondary
Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 1.01 Microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 20.81 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 16.2 Microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 25.9 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 69.2 Microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 28.63 |
Secondary
Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B
Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.
Time frame: Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 56 | 2.46 mcg/mL | Geometric Coefficient of Variation 15.27 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 63 | 1.28 mcg/mL | Geometric Coefficient of Variation 18.54 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 70 | 1.54 mcg/mL | Geometric Coefficient of Variation 32.36 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 77 | 1.17 mcg/mL | Geometric Coefficient of Variation 22.44 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 84 | 1.17 mcg/mL | Geometric Coefficient of Variation 19.75 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 91 | 5.15 mcg/mL | Geometric Coefficient of Variation 19.32 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 98 | 2.77 mcg/mL | Geometric Coefficient of Variation 16.41 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 105 | 2.96 mcg/mL | Geometric Coefficient of Variation 19.79 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 112 | 3.22 mcg/mL | Geometric Coefficient of Variation 15.5 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 56 | 40.9 mcg/mL | Geometric Coefficient of Variation 25.31 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 63 | 85.5 mcg/mL | Geometric Coefficient of Variation 40.91 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 70 | 80.3 mcg/mL | Geometric Coefficient of Variation 37.07 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 77 | 87.1 mcg/mL | Geometric Coefficient of Variation 41.84 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 84 | 89.1 mcg/mL | Geometric Coefficient of Variation 52.79 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 91 | 136 mcg/mL | Geometric Coefficient of Variation 41.37 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 98 | 201 mcg/mL | Geometric Coefficient of Variation 33.19 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 105 | 194 mcg/mL | Geometric Coefficient of Variation 44.14 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 112 | 200 mcg/mL | Geometric Coefficient of Variation 31.58 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 56 | 169 mcg/mL | Geometric Coefficient of Variation 25.28 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 63 | 366 mcg/mL | Geometric Coefficient of Variation 38.19 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 70 | 309 mcg/mL | Geometric Coefficient of Variation 38.95 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 77 | 337 mcg/mL | Geometric Coefficient of Variation 43.45 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 84 | 345 mcg/mL | Geometric Coefficient of Variation 50.8 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 91 | 522 mcg/mL | Geometric Coefficient of Variation 35.93 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 98 | 788 mcg/mL | Geometric Coefficient of Variation 25.66 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 105 | 748 mcg/mL | Geometric Coefficient of Variation 27.21 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 112 | 670 mcg/mL | Geometric Coefficient of Variation 33.48 |
Secondary
Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C
Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.
Time frame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Plasma - Day 28 | 2.66 mcg/mL | Geometric Coefficient of Variation 78.79 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Plasma - Day 42 | 4.25 mcg/mL | Geometric Coefficient of Variation 81.86 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Whole Blood - Day 28 | 166 mcg/mL | Geometric Coefficient of Variation 126.31 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Whole Blood - Day 42 | 175 mcg/mL | Geometric Coefficient of Variation 141.04 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | RBC concentration - Day 28 | 531 mcg/mL | Geometric Coefficient of Variation 105.76 |
| Part A: Single Dose Period | Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | RBC concentration - Day 42 | 540 mcg/mL | Geometric Coefficient of Variation 125.43 |
Secondary
Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B
Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation.
Time frame: Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 63 | 0.97 mcg/mL | Geometric Coefficient of Variation 27.41 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 70 | 0.98 mcg/mL | Geometric Coefficient of Variation 22.18 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 77 | 0.90 mcg/mL | Geometric Coefficient of Variation 20.38 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 84 | 0.884 mcg/mL | Geometric Coefficient of Variation 21.58 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 91 | 0.90 mcg/mL | Geometric Coefficient of Variation 30.51 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 98 | 1.94 mcg/mL | Geometric Coefficient of Variation 24.77 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 105 | 1.84 mcg/mL | Geometric Coefficient of Variation 27.55 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Plasma- Day 112 | 2.03 mcg/mL | Geometric Coefficient of Variation 24.43 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 63 | 62.6 mcg/mL | Geometric Coefficient of Variation 42.01 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 70 | 72.8 mcg/mL | Geometric Coefficient of Variation 36.26 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 77 | 77.4 mcg/mL | Geometric Coefficient of Variation 45.27 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 84 | 70.8 mcg/mL | Geometric Coefficient of Variation 67.54 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 91 | 76.5 mcg/mL | Geometric Coefficient of Variation 49.02 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 98 | 172 mcg/mL | Geometric Coefficient of Variation 43.11 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 105 | 161 mcg/mL | Geometric Coefficient of Variation 45 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | Whole Blood- Day 112 | 182 mcg/mL | Geometric Coefficient of Variation 31.55 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 63 | 267 mcg/mL | Geometric Coefficient of Variation 41.68 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 70 | 280 mcg/mL | Geometric Coefficient of Variation 38.56 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 77 | 299 mcg/mL | Geometric Coefficient of Variation 46.55 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 84 | 274 mcg/mL | Geometric Coefficient of Variation 65.32 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 91 | 299 mcg/mL | Geometric Coefficient of Variation 43.5 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 98 | 674 mcg/mL | Geometric Coefficient of Variation 34.28 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 105 | 621 mcg/mL | Geometric Coefficient of Variation 26.23 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B | RBC concentration- Day 112 | 620 mcg/mL | Geometric Coefficient of Variation 34.72 |
Secondary
Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C
Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation.
Time frame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Plasma - Day 28 | 1.54 mcg/mL | Geometric Coefficient of Variation 220.43 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Plasma - Day 42 | 1.99 mcg/mL | Geometric Coefficient of Variation 264.95 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Whole Blood - Day 28 | 122 mcg/mL | Geometric Coefficient of Variation 211.47 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | Whole Blood - Day 42 | 140 mcg/mL | Geometric Coefficient of Variation 217.11 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | RBC concentration - Day 28 | 392 mcg/mL | Geometric Coefficient of Variation 174.41 |
| Part A: Single Dose Period | Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C | RBC concentration - Day 42 | 433 mcg/mL | Geometric Coefficient of Variation 187.77 |
Secondary
Percentage Hemoglobin Occupancy
Percentage hemoglobin occupancy (%Hb Occupancy) refers to the proportion of hemoglobin molecules within red blood cells that were bound to study drug (GBT021601). Cmin and Cmax values was used to calculate %Hb occupancy: %Hb Occupancy = GBT021601\*RBC per Mean Corpuscular Hemoglobin Concentration (MCHC).
Time frame: Part A: Pre-dose,0.25,0.5,1,2,4, 6,8,12,24,36,48,72,168,336,504,672,1008 hrs on Day 1; Part B: Pre-dose,0.25 to 1,2 to 4 hrs post-dose on Day 56,63,70,77,84,91,98,105,112; Part C:Pre-dose on Day 1,14,28,42 and 0.25 to 1, 2 to 4 hrs post-dose on Day 28,42
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Percentage Hemoglobin Occupancy | Part A: Cmax- Day 1 | 3.36 Percentage of Hemoglobin | Standard Deviation 0.86 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 56 | 8.15 Percentage of Hemoglobin | Standard Deviation 1.89 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax - Day 63 | 18.15 Percentage of Hemoglobin | Standard Deviation 5.96 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 63 | 13.40 Percentage of Hemoglobin | Standard Deviation 4.71 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 70 | 15.50 Percentage of Hemoglobin | Standard Deviation 5.11 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 70 | 14.03 Percentage of Hemoglobin | Standard Deviation 4.69 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 77 | 17.03 Percentage of Hemoglobin | Standard Deviation 6 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 77 | 15.25 Percentage of Hemoglobin | Standard Deviation 5.54 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 84 | 17.66 Percentage of Hemoglobin | Standard Deviation 7.75 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 84 | 14.57 Percentage of Hemoglobin | Standard Deviation 7.29 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 91 | 25.71 Percentage of Hemoglobin | Standard Deviation 7.92 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 91 | 15.02 Percentage of Hemoglobin | Standard Deviation 5.85 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 98 | 38.00 Percentage of Hemoglobin | Standard Deviation 9.05 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 98 | 33.04 Percentage of Hemoglobin | Standard Deviation 9.31 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 105 | 36.11 Percentage of Hemoglobin | Standard Deviation 9.14 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 105 | 29.89 Percentage of Hemoglobin | Standard Deviation 7.21 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmax- Day 112 | 32.68 Percentage of Hemoglobin | Standard Deviation 9.33 |
| Part B: Multiple Ascending- Dose Period | Percentage Hemoglobin Occupancy | Part B: Cmin- Day 112 | 30.32 Percentage of Hemoglobin | Standard Deviation 8.92 |
| Part C: Extended Treatment Period | Percentage Hemoglobin Occupancy | Part C: Cmax- Day 28 | 31.45 Percentage of Hemoglobin | Standard Deviation 17.97 |
| Part C: Extended Treatment Period | Percentage Hemoglobin Occupancy | Part C: Cmin- Day 28 | 26.54 Percentage of Hemoglobin | Standard Deviation 16.96 |
| Part C: Extended Treatment Period | Percentage Hemoglobin Occupancy | Part C: Cmax- Day 42 | 33.13 Percentage of Hemoglobin | Standard Deviation 19.12 |
| Part C: Extended Treatment Period | Percentage Hemoglobin Occupancy | Part C: Cmin- Day 42 | 29.46 Percentage of Hemoglobin | Standard Deviation 18.09 |
Secondary
Plasma Concentrations Versus Time Summary of GBT021601: Part A
The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose | 0 mcg/mL | Standard Deviation 0 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 0.25 hour | 0.145 mcg/mL | Standard Deviation 0.137 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 0.5 hour | 0.617 mcg/mL | Standard Deviation 0.281 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 1 hour | 0.910 mcg/mL | Standard Deviation 0.312 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 2 hours | 0.821 mcg/mL | Standard Deviation 0.202 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 4 hours | 0.498 mcg/mL | Standard Deviation 0.15 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 6 hours | 0.350 mcg/mL | Standard Deviation 0.1 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 8 hours | 0.279 mcg/mL | Standard Deviation 0.737 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 12 hours | 0.228 mcg/mL | Standard Deviation 0.04 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 24 hours | 0.257 mcg/mL | Standard Deviation 0.12 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 36 hours | 0.333 mcg/mL | Standard Deviation 0.286 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 48 hours | 0.183 mcg/mL | Standard Deviation 0.067 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 72 hours | 0.138 mcg/mL | Standard Deviation 0.019 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 168 hours | 0.124 mcg/mL | Standard Deviation 0.02 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 336 hours | 0.0786 mcg/mL | Standard Deviation 0.016 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 504 hours | 0.047 mcg/mL | Standard Deviation 0.016 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 672 hours | 0.029 mcg/mL | Standard Deviation 0.137 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part A | 1008 hours | 0.013 mcg/mL | Standard Deviation 0.007 |
Secondary
Plasma Concentrations Versus Time Summary of GBT021601: Part B
The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.
Time frame: Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 56: Pre-dose | 0.143 mcg/mL | Standard Deviation 0.351 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 56 :0.25-1 hour | 1.163 mcg/mL | Standard Deviation 1.165 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 56: 2-4 hours | 2.345 mcg/mL | Standard Deviation 0.3129 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 63: Pre-dose | 1.015 mcg/mL | Standard Deviation 0.24 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 0.25-1 hour | 1.148 mcg/mL | Standard Deviation 0.268 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 2-4 hours | 1.250 mcg/mL | Standard Deviation 0.21 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 70: Pre-dose | 1.003 mcg/mL | Standard Deviation 0.211 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 0.25-1 hour | 1.376 mcg/mL | Standard Deviation 0.653 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 2-4 hours | 1.415 mcg/mL | Standard Deviation 0.262 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 77: Pre-dose | 0.937 mcg/mL | Standard Deviation 0.151 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 0.25-1 hour | 1.103 mcg/mL | Standard Deviation 0.318 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 2-4 hours | 1.173 mcg/mL | Standard Deviation 0.233 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 84: Pre-dose | 0.918 mcg/mL | Standard Deviation 0.176 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 84 :0.25-1 hour | 1.085 mcg/mL | Standard Deviation 0.284 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 84: 2-4 hours | 1.097 mcg/mL | Standard Deviation 0.205 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 91: Pre-dose | 0.941 mcg/mL | Standard Deviation 0.278 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 91; 0.25-1 hour | 3.019 mcg/mL | Standard Deviation 2.225 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 91: 2-4 hours | 4.990 mcg/mL | Standard Deviation 0.635 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 98: Pre-dose | 2.118 mcg/mL | Standard Deviation 0.687 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 0.25-1 hour | 2.242 mcg/mL | Standard Deviation 0.398 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 2-4 hours | 2.580 mcg/mL | Standard Deviation 0.53933 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 105: Pre-dose | 1.945 mcg/mL | Standard Deviation 0.57 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 0.25-1 hour | 2.147 mcg/mL | Standard Deviation 0.47 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 2-4 hours | 2.953 mcg/mL | Standard Deviation 0.642 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 112 :Predose | 2.095 mcg/mL | Standard Deviation 0.242 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 0.25-1 hour | 2.748 mcg/mL | Standard Deviation 0.824 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 2-4 hours | 2.905 mcg/mL | Standard Deviation 0.688 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 140: 2-4 hours | 0.225 mcg/mL | Standard Deviation 0.0516 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 168: 2-4 hours | 0.042 mcg/mL | Standard Deviation 0.026 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 196: 2-4 hours | 0.005 mcg/mL | Standard Deviation 0.005 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part B | Day 218: 2-4 hours | 0.000 mcg/mL | Standard Deviation 0.001 |
Secondary
Plasma Concentrations Versus Time Summary of GBT021601: Part C
The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.
Time frame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 28: Pre-dose | 2.448 mcg/mL | Standard Deviation 1.786 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 28: 4 hours | 2.991 mcg/mL | Standard Deviation 1.476 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 42: Pre-dose | 3.621 mcg/mL | Standard Deviation 2.929 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 0.25-1 hour | 4.285 mcg/mL | Standard Deviation 2.785 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 2-4 hours | 4.485 mcg/mL | Standard Deviation 2.308 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 70: 2-4 hours | 0.364 mcg/mL | Standard Deviation 0.101 |
| Part A: Single Dose Period | Plasma Concentrations Versus Time Summary of GBT021601: Part C | Day 98: 2-4 hours | 0.034 mcg/mL | Standard Deviation 0.011 |
Secondary
Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A
The RBC concentration versus time summary was measured to identify quantity of RBC in a sample of blood over a specified duration. This analysis helped monitor RBC level over time.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose | 0 mcg/mL | Standard Deviation 0 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 0.25 hour | 3.989 mcg/mL | Standard Deviation 3.314 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 0.5 hour | 18.68 mcg/mL | Standard Deviation 10.413 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 1 hour | 34.84 mcg/mL | Standard Deviation 16.282 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 2 hours | 52.51 mcg/mL | Standard Deviation 14.931 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 4 hours | 59.50 mcg/mL | Standard Deviation 14.281 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 6 hours | 61.72 mcg/mL | Standard Deviation 15.356 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 8 hours | 61.68 mcg/mL | Standard Deviation 13.932 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 12 hours | 62.24 mcg/mL | Standard Deviation 18.34 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 24 hours | 61.92 mcg/mL | Standard Deviation 16.283 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 36 hours | 65.62 mcg/mL | Standard Deviation 18.78 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 48 hours | 56.60 mcg/mL | Standard Deviation 14.463 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 72 hours | 53.68 mcg/mL | Standard Deviation 15.728 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 168 hours | 42.41 mcg/mL | Standard Deviation 12.26 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 336 hours | 22.73 mcg/mL | Standard Deviation 6.316 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 504 hours | 16.65 mcg/mL | Standard Deviation 4.931 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 672 hours | 9.207 mcg/mL | Standard Deviation 5.652 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A | 1008 hours | 4.073 mcg/mL | Standard Deviation 3.186 |
Secondary
Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B
The RBC concentration versus time summary was measured to identify quantity of RBC in a sample of blood over a specified duration. This analysis helped monitor RBC level over time.
Time frame: Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 56: Pre-dose | 0.120 mcg/mL | Standard Deviation 0.134 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 56 :0.25-1 hour | 52.57 mcg/mL | Standard Deviation 53.388 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 56: 2-4 hours | 170.8 mcg/mL | Standard Deviation 45.616 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 63: Pre-dose | 317.4 mcg/mL | Standard Deviation 126.93 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 0.25-1 hour | 375.4 mcg/mL | Standard Deviation 134.89 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 2-4 hours | 318.6 mcg/mL | Standard Deviation 83.313 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 70: Pre-dose | 304.7 mcg/mL | Standard Deviation 105.71 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 0.25-1 hour | 313.9 mcg/mL | Standard Deviation 97.32 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 2-4 hours | 314.7 mcg/mL | Standard Deviation 106.95 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 77: Pre-dose | 335.9 mcg/mL | Standard Deviation 130.15 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 0.25-1 hour | 340.1 mcg/mL | Standard Deviation 118.67 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 2-4 hours | 343.8 mcg/mL | Standard Deviation 120.89 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 84: Pre-dose | 338.6 mcg/mL | Standard Deviation 169.41 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 84 :0.25-1 hour | 344.7 mcg/mL | Standard Deviation 170.26 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 84: 2-4 hours | 356.0 mcg/mL | Standard Deviation 144.12 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 91: Pre-dose | 329.0 mcg/mL | Standard Deviation 124.33 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 91; 0.25-1 hour | 392.6 mcg/mL | Standard Deviation 197.92 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 91: 2-4 hours | 547.7 mcg/mL | Standard Deviation 173.83 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 98: Pre-dose | 753.5 mcg/mL | Standard Deviation 207.85 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 0.25-1 hour | 726.2 mcg/mL | Standard Deviation 215.42 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 2-4 hours | 768.9 mcg/mL | Standard Deviation 164.84 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 105: Pre-dose | 711.7 mcg/mL | Standard Deviation 148.81 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 0.25-1 hour | 662.4 mcg/mL | Standard Deviation 190.38 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 2-4 hours | 752.8 mcg/mL | Standard Deviation 222.08 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 112: Predose | 705.6 mcg/mL | Standard Deviation 209.26 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 0.25-1 hour | 674.3 mcg/mL | Standard Deviation 201.56 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 2-4 hours | 666.7 mcg/mL | Standard Deviation 206.56 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 140: 2-4 hours | 120.8 mcg/mL | Standard Deviation 83.588 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 168: 2-4 hours | 14.97 mcg/mL | Standard Deviation 9.339 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 196: 2-4 hours | 2.326 mcg/mL | Standard Deviation 2.226 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B | Day 218: 2-4 hours | 0.850 mcg/mL | Standard Deviation 0.539 |
Secondary
Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C
The RBC concentration versus time summary involved tracking a quantity of RBC in a sample of blood over a specified duration. This analysis helped to monitor RBC level over time.
Time frame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 0.25-1 hour | 639.8 mcg/mL | Standard Deviation 361.11 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 28: Pre-dose | 621.3 mcg/mL | Standard Deviation 428.95 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 28: 4 hours | 594.4 mcg/mL | Standard Deviation 319.62 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 42: Pre-dose | 642.4 mcg/mL | Standard Deviation 396.97 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 2-4 hours | 691.1 mcg/mL | Standard Deviation 404.73 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 70: 2-4 hours | 117.9 mcg/mL | Standard Deviation 20.028 |
| Part A: Single Dose Period | Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C | Day 98: 2-4 hours | 12.74 mcg/mL | Standard Deviation 3.256 |
Secondary
Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
t1/2 was the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Single Dose Period | Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 236.191 hr |
| Part A: Single Dose Period | Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 230.908 hr |
| Part A: Single Dose Period | Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 231.272 hr |
Secondary
Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
Maximum observed concentration was defined as the peak concentration observed directly from the experimental data without any interpolation. The time to the maximum observed concentration was defined as the time corresponding to Cmax.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Single Dose Period | Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Plasma | 1.50 Hours |
| Part A: Single Dose Period | Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | Whole Blood | 8.06 Hours |
| Part A: Single Dose Period | Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A | RBC concentration | 8.06 Hours |
Secondary
Whole Blood Concentrations Versus Time Summary of GBT021601: Part A
The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time.
Time frame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | Pre-dose | 0 mcg/mL | Standard Deviation 0 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 0.25 hour | 1.034 mcg/mL | Standard Deviation 0.876 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 0.5 hour | 4.775 mcg/mL | Standard Deviation 2.47 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 1 hour | 8.745 mcg/mL | Standard Deviation 3.833 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 2 hours | 12.710 mcg/mL | Standard Deviation 3.19 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 4 hours | 14.07 mcg/mL | Standard Deviation 2.917 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 6 hours | 14.44 mcg/mL | Standard Deviation 2.98 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 8 hours | 14.42 mcg/mL | Standard Deviation 2.861 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 12 hours | 14.45 mcg/mL | Standard Deviation 3.811 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 24 hours | 14.42 mcg/mL | Standard Deviation 3.22 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 36 hours | 15.41 mcg/mL | Standard Deviation 4.22 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 48 hours | 13.14 mcg/mL | Standard Deviation 2.895 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 72 hours | 12.42 mcg/mL | Standard Deviation 3.193 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 168 hours | 9.847 mcg/mL | Standard Deviation 2.562 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 336 hours | 5.282 mcg/mL | Standard Deviation 1.283 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 504 hours | 3.870 mcg/mL | Standard Deviation 1.071 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 672 hours | 2.138 mcg/mL | Standard Deviation 1.283 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part A | 1008 hours | 0.943 mcg/mL | Standard Deviation 0.729 |
Secondary
Whole Blood Concentrations Versus Time Summary of GBT021601: Part B
The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time.
Time frame: Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs, post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112, 140,168, 196, 218
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 56: Pre-dose | 0.071 mcg/mL | Standard Deviation 0.085 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 56: 0.25-1 hour | 13.20 mcg/mL | Standard Deviation 13.601 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 56: 2-4 hours | 41.23 mcg/mL | Standard Deviation 10.318 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 63: Pre-dose | 74.32 mcg/mL | Standard Deviation 30.266 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 0.25-1 hour | 88.23 mcg/mL | Standard Deviation 33.335 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 63: 2- 4 hours | 74.87 mcg/mL | Standard Deviation 19.748 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 70: Pre-dose | 78.28 mcg/mL | Standard Deviation 24.403 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 0.25-1 hour | 81.00 mcg/mL | Standard Deviation 22.709 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 70: 2-4 hours | 81.25 mcg/mL | Standard Deviation 25.669 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 77: Pre-dose | 86.22 mcg/mL | Standard Deviation 30.703 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 0.25-1 hour | 87.33 mcg/mL | Standard Deviation 27.507 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 77: 2- 4 hours | 88.68 mcg/mL | Standard Deviation 29.043 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 84: Predose | 87.77 mcg/mL | Standard Deviation 43.076 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 84 :0.25-1 hour | 88.97 mcg/mL | Standard Deviation 42.685 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 84: 2-4 hours | 92.05 mcg/mL | Standard Deviation 36.53 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 91: Pre-dose | 85.07 mcg/mL | Standard Deviation 32.859 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 91; 0.25-1 hour | 102.4 mcg/mL | Standard Deviation 52.161 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 91: 2-4 hours | 144.1 mcg/mL | Standard Deviation 47.113 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 98: Pre-dose | 195.8 mcg/mL | Standard Deviation 61.979 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 0.25-1 hour | 188.8 mcg/mL | Standard Deviation 61.802 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 98: 2-4 hours | 198.8 mcg/mL | Standard Deviation 49.301 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 105: Pre-dose | 189.8 mcg/mL | Standard Deviation 56.672 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 0.25-1 hour | 178.9 mcg/mL | Standard Deviation 66.612 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 105: 2-4 hours | 203.3 mcg/mL | Standard Deviation 74.923 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 112: Pre-dose | 195.0 mcg/mL | Standard Deviation 59.117 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 0.25-1 hour | 200.5 mcg/mL | Standard Deviation 57.263 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 112: 2-4 hours | 198.5 mcg/mL | Standard Deviation 59.248 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 140: 2-4 hours | 29.32 mcg/mL | Standard Deviation 20.149 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 168: 2-4 hours | 3.082 mcg/mL | Standard Deviation 2.137 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 196: 2-4 hours | 0.561 mcg/mL | Standard Deviation 0.56 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part B | Day 218: 2-4 hours | 0.108 mcg/mL | Standard Deviation 0.109 |
Secondary
Whole Blood Concentrations Versus Time Summary of GBT021601: Part C
The whole blood concentration versus time summary was measured to find concentration of various components in whole blood that changed over a specified period. This helped to monitor the dynamics of blood components such as hemoglobin levels, hematocrit, or glucose concentration over time.
Time frame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
Population: Pharmacokinetic population was defined as all participants who received at least 1 dose of study drug (GBT021601) and had at least 1 plasma or whole blood concentration data point. Here, 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 28: Pre-dose | 202.2 mcg/mL | Standard Deviation 136.32 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 28: 4 hours | 193.6 mcg/mL | Standard Deviation 106.16 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 42: Pre-dose | 214.8 mcg/mL | Standard Deviation 131.21 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 0.25-1 hour | 213.5 mcg/mL | Standard Deviation 119.79 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 42: 2- 4 hours | 229.9 mcg/mL | Standard Deviation 132.21 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 70: 2-4 hours | 33.50 mcg/mL | Standard Deviation 2.553 |
| Part A: Single Dose Period | Whole Blood Concentrations Versus Time Summary of GBT021601: Part C | Day 98: 2-4 hours | 3.310 mcg/mL | Standard Deviation 0.826 |