A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)

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.

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.

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.

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.

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).

Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.

Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.

Cmax was defined as the peak concentration observed directly from the experimental data without any interpolation.

Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation.

Cmin was defined as the lowest concentration observed directly from the experimental data without any interpolation.

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.

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.

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.

AUC0-24 was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.

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.

t1/2 was the time measured for the plasma concentration to decrease by one half.

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 (%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).

The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.

The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.

The plasma concentration versus time summary was measured by the amount of specific substance in the bloodstream over the specified timepoint.

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.

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.

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.

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.

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.

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.