Sickle Cell Disease
Conditions
Brief summary
This study consists of four parts, Parts A, B, C, and D. * Part A is a single dose pharmacokinetic (PK) study in pediatric participants with Sickle Cell Disease ages 6 to 17 years. * Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent participants with Sickle Cell Disease ages 12 to 17 years. * Part C is a multiple dose, safety, tolerability, and PK study, which includes the assessment of hematological effects and the effect on TCD flow velocity of voxelotor in pediatric participants with Sickle Cell Disease ages 4 to 17 years. * Part D is a multiple dose, safety, tolerability, and PK study, which examines the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease ages 6 months to \< 4 years.
Interventions
DRUGVoxelotor
* Part A: Voxelotor will be administered as oral capsules or tablets * Part B: Voxelotor will be administered as oral capsules or tablets * Part C: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension * Part D: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal) * Age: * Part A - 6 to 17 years of age * Part B - 12 to 17 years of age * Part C - 4 to 17 years of age * Part D - 6 months to \<4 years of age * Hydroxyurea (HU) therapy: * Parts A, B, and C: A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity. * Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study. * Hemoglobin (HB): * Part A - No restriction * Parts B, C, & D - Hb ≤ 10.5 g/dL * For Part C only: Participants 12 to 17 years of age must have a TCD velocity of ≥ 140 cm/sec measured anytime during screening.
Exclusion criteria
* Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF): * Vaso-occlusive crisis (VOC) * Acute chest syndrome (ACS) * Splenic sequestration crisis * Dactylitis * Requires chronic transfusion therapy * History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements ≥ 200 cm/sec by non-imaging TCD or ≥185 cm/sec by TCDi). * Transfusion within 30 days prior to signing the ICF
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Maximum Concentration (Cmax) of Voxelotor in Whole Blood | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Whole Blood | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | AUC0-last was calculated using the linear/log trapezoid rule. |
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Whole Blood | pre-dose, 2, 8, 24, 48, 96,168 and 336 hours post-dose | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for whole blood and lambdaz=elimination rate constant. |
| Part B: Change From Baseline to Week 24 in Hemoglobin Level | Baseline, Week 24 | — |
| Part C: Change From Baseline to Week 48 in Cerebral Blood Flow | Baseline, Week 48 | Cerebral blood flow was measured using transcranial Doppler (TCD) sonography. Change from baseline in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity is reported. |
| Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From start of study treatment up to 28 days after study treatment discontinuation (Up to 52 weeks) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. TEAE was defined as an AE that emerged on or after initiation of study drug (having been absent pre-treatment), or an AE that existed pre-treatment and worsened on treatment (relative to the pre-treatment state) through 28 days after study drug discontinuation. An SAE was any AE that resulted in any of the following outcomes: death, life threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, other important medical events. AEs were classified as SCD-related and non-SCD related. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in RBC | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant. |
| Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Whole Blood | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Plasma | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in RBC | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Whole Blood | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Plasma | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in RBC | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part A: Percentage Hemoglobin (Hb) Occupancy | 15 days | Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100. |
| Part B: Percentage of Days With SCD Symptom Exacerbation During the First 24 Weeks of Treatment | From Day 1 up to 24 weeks | SCD symptoms were measured using the Patient Reported Outcome (PRO), Sickle Cell Disease Severity Measure (SCDSM) which was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale that was completed daily using a handheld electronic device by the participants. |
| Part B: Change From Baseline to Week 21 to 24 in the Sickle Cell Disease Severity Measure (SCDSM) Total Symptom Score (TSS) | Baseline, Weeks 21 to 24 | The SCDSM was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale with a range of 0 (strongly disagree) to 4 (strongly agree) that was completed daily using a handheld electronic device by the participants. TSS was calculated as the sum of the 9-item questionnaire scores scaled to a 100-point scale with a range of 0 (no symptoms) to 100 (most severe symptoms). Baseline TSS was the average of the non-missing score during the Screening period. The average of change from baseline in SCDSM TSS score for the 4-week period (Week 21 to 24) is reported. |
| Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH) | Baseline, Weeks 12 and 24 | — |
| Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin | Baseline, Weeks 12 and 24 | — |
| Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes | Baseline, Weeks 12 and 24 | — |
| Part B: Cmax of Voxelotor in Whole Blood and Plasma | Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24 | — |
| Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood | Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24 | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood | Day 1 (0 to 24 hours post-dose) and Day 28 (0 to 24 hours post-dose) | Accumulation ratio was calculated as ratio of area under the concentration-time curve from time 0 to 24 hours (AUC0-24) at steady-state (Day 28) to AUC0-24 on Day 1. |
| Part B: Percentage Hemoglobin Occupancy | Day 28 | Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100. |
| Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow | Baseline, Weeks 12 and 24 | Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported. |
| Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Baseline, Weeks 24 and 48 | — |
| Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH | Baseline, Weeks 24 and 48 | — |
| Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Baseline, Weeks 24 and 48 | — |
| Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes | Baseline, Weeks 24 and 48 | — |
| Part C: Change From Baseline to Week 24 in Cerebral Blood Flow | Baseline, Week 24 | Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported. |
| Part C: Time to Initial Hemoglobin Response | From first dose of study treatment (Day 1) up to Week 48 | Time to initial Hb response was defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb \> 1 gram per deciliter (g/dL). |
| Part C: Cmax of Voxelotor for Plasma and Whole Blood | Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48 | — |
| Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48 | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant. |
| Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma | Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48 | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part C: Percentage Hemoglobin Occupancy of Voxelotor | Day 28 | Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100. |
| Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48 | Week 48 | Normal TCD flow velocity was considered as \< 170 centimeter per second (cm/sec) by non-imagining TCD or \< 155 cm/sec by imaging transcranial Doppler (TCDi). Percentage of participants with normal TCD flow velocity at Week 48 by Baseline TCD group (i.e. Baseline normal TCD \[\<170 cm/sec\] and Baseline conditional TCD \[\>=170 cm/sec\] is reported. |
| Part C: Annualized Incidence Rate of Vaso-occlusive Crisis (VOC) Events | Up to Week 48 | VOC events included preferred terms of sickle cell anaemia with crisis, acute chest syndrome, pneumonia necrotising and pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose. |
| Part C: Annualized Incidence Rate of Stroke Events | Up to Week 48 | Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose. |
| Part D: Cmax of Voxelotor for Plasma and Whole Blood | Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48 | — |
| Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood | Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48 | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant. |
| Part D: T1/2 of Voxelotor for Plasma and Whole Blood | Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48 | T1/2 was the time measured for the drug concentration to decrease by one half. |
| Part D: Percentage Hemoglobin Occupancy | Day 28 | Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100. |
| Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Baseline, Weeks 24 and 48 | — |
| Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH | Baseline, Weeks 24 and 48 | — |
| Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Baseline, Weeks 24 and 48 | — |
| Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count | Baseline, Weeks 24 and 48 | — |
| Part D: Time to Initial Hemoglobin Response | From first dose of study treatment (Day 1) up to Week 48 | Time to initial Hb response, defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb \> 1 g/dL. |
| Part D: Annualized Incidence Rate of VOC Events | Up to Week 48 | VOC events included preferred terms of 'Sickle cell anemia with crisis', 'Acute chest syndrome', 'Pneumonia necrotising,' and 'Pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose. |
| Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24 | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant. |
| Part D: Annualized Incidence Rate of Stroke Events | Up to Week 48 | Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose. |
| Part A: Maximum Concentration (Cmax) of Voxelotor in Plasma | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Maximum Concentration (Cmax) of Voxelotor in Red Blood Cells (RBC) | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | — |
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Plasma | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | AUC0-last was calculated using the linear/log trapezoid rule. |
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in RBC | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | AUC0-last was calculated using the linear/log trapezoid rule. |
| Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Plasma | pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose | AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for plasma and lambdaz is the elimination rate constant. |
Countries
Lebanon, United Kingdom, United States
Participant flow
Recruitment details
This study consisted of four parts-Part A, B, C and D. The study was terminated as the emerging clinical data indicated that the risk profile of voxelotor in people with sickle cell disease (SCD) exceeded the benefits observed in previously generated global research and required further assessment.
Pre-assignment details
A total of 147 pediatric participants with SCD (13 in Part A, 40 in Part B, 62 in Part C and 32 in Part D) were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg Participants aged 12 to 17 years received a single oral dose of voxelotor 600 milligrams (mg) on Day 1. | 7 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg Participants aged 6 to 11 years received a single oral dose of voxelotor 600 mg on Day 1. | 6 |
| Part B: Voxelotor 900 mg QD Participants aged 12 to 17 years received once daily (QD) oral dose of voxelotor 900 mg for 24 weeks. | 25 |
| Part B: Voxelotor 1500 mg QD Participants aged 12 to 17 years received once daily oral dose of voxelotor 1500 mg for 24 weeks. | 15 |
| Part C: Participants Aged 4 to 11 Years: Voxelotor 1500 mg QD Participants aged 4 to 11 years received once daily oral dose of voxelotor 1500 mg for 48 weeks. | 51 |
| Part C: Participants Aged 12 to 17 Years: Voxelotor 1500 mg QD Participants aged 12 to 17 years received once daily oral dose of voxelotor 1500 mg for 48 weeks. | 11 |
| Part D: Participants Aged 6 Months to <2 Years: Voxelotor 1500 mg QD Participants aged 6 months to \<2 years received once daily oral dose of voxelotor 1500 mg for 48 weeks. | 9 |
| Part D: Participants Aged 2 to <4 Years: Voxelotor 1500 mg QD Participants aged 2 to \<4 years received once daily oral dose of voxelotor 1500 mg for 48 weeks. | 23 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part B (Up to 28 Weeks) | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part B (Up to 28 Weeks) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B (Up to 28 Weeks) | Non compliance | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B (Up to 28 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Part C (Up to 52 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 4 | 2 | 0 | 0 |
| Part C (Up to 52 Weeks) | Other | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 |
| Part C (Up to 52 Weeks) | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part C (Up to 52 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 6 | 3 | 0 | 0 |
| Part D (Up to 52 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part D (Up to 52 Weeks) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part D (Up to 52 Weeks) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Part D (Up to 52 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Voxelotor 900 mg QD | Part B: Voxelotor 1500 mg QD | Part C: Participants Aged 4 to 11 Years: Voxelotor 1500 mg QD | Part C: Participants Aged 12 to 17 Years: Voxelotor 1500 mg QD | Part D: Participants Aged 6 Months to <2 Years: Voxelotor 1500 mg QD | Part D: Participants Aged 2 to <4 Years: Voxelotor 1500 mg QD | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 15.4 Years STANDARD_DEVIATION 0.79 | 8.2 Years STANDARD_DEVIATION 1.72 | 14.0 Years STANDARD_DEVIATION 1.68 | 13.9 Years STANDARD_DEVIATION 1.58 | 7.3 Years STANDARD_DEVIATION 2.06 | 13.1 Years STANDARD_DEVIATION 1.04 | 1.4 Years STANDARD_DEVIATION 0.41 | 3.0 Years STANDARD_DEVIATION 0.51 | 8.9 Years STANDARD_DEVIATION 4.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 24 Participants | 14 Participants | 48 Participants | 11 Participants | 8 Participants | 22 Participants | 140 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Arab/Middle Eastern | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 3 Participants | 18 Participants | 11 Participants | 44 Participants | 11 Participants | 5 Participants | 9 Participants | 104 Participants |
| Race/Ethnicity, Customized Middle Eastern or North African | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Multi-racial | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants | 6 Participants | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 9 Participants | 28 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 11 Participants | 10 Participants | 27 Participants | 4 Participants | 3 Participants | 9 Participants | 71 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 14 Participants | 5 Participants | 24 Participants | 7 Participants | 6 Participants | 14 Participants | 76 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 25 | 0 / 15 | 0 / 51 | 0 / 11 | 0 / 9 | 0 / 23 |
| other Total, other adverse events | 6 / 7 | 3 / 6 | 22 / 25 | 15 / 15 | 46 / 51 | 11 / 11 | 9 / 9 | 21 / 23 |
| serious Total, serious adverse events | 1 / 7 | 0 / 6 | 12 / 25 | 7 / 15 | 23 / 51 | 8 / 11 | 7 / 9 | 14 / 23 |
Outcome results
Primary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Whole Blood
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for whole blood and lambdaz=elimination rate constant.
Time frame: pre-dose, 2, 8, 24, 48, 96,168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Whole Blood | 1520000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 40.98 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Whole Blood | 2570000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 50.59 |
Primary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Whole Blood
AUC0-last was calculated using the linear/log trapezoid rule.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Whole Blood | 1570000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 38.13 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Whole Blood | 2540000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 50.25 |
Primary
Part A: Maximum Concentration (Cmax) of Voxelotor in Whole Blood
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: Pharmacokinetic (PK) population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Whole Blood | 24300 Nanogram per milliliter | Geometric Coefficient of Variation 36.39 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Whole Blood | 47300 Nanogram per milliliter | Geometric Coefficient of Variation 43.62 |
Primary
Part B: Change From Baseline to Week 24 in Hemoglobin Level
Time frame: Baseline, Week 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 24 in Hemoglobin Level | 0.7 Gram per deciliter | Standard Deviation 0.86 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 24 in Hemoglobin Level | 0.2 Gram per deciliter | Standard Deviation 1.02 |
Primary
Part C: Change From Baseline to Week 48 in Cerebral Blood Flow
Cerebral blood flow was measured using transcranial Doppler (TCD) sonography. Change from baseline in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity is reported.
Time frame: Baseline, Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Change From Baseline to Week 48 in Cerebral Blood Flow | -0.4 Centimeter per second | Standard Deviation 16.76 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Change From Baseline to Week 48 in Cerebral Blood Flow | -26.3 Centimeter per second | Standard Deviation 11.59 |
Primary
Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. TEAE was defined as an AE that emerged on or after initiation of study drug (having been absent pre-treatment), or an AE that existed pre-treatment and worsened on treatment (relative to the pre-treatment state) through 28 days after study drug discontinuation. An SAE was any AE that resulted in any of the following outcomes: death, life threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, other important medical events. AEs were classified as SCD-related and non-SCD related.
Time frame: From start of study treatment up to 28 days after study treatment discontinuation (Up to 52 weeks)
Population: Safety population comprised of all participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Non-SCD related TEAEs | 9 Participants |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Non-SCD related SAEs | 6 Participants |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SCD related TEAEs | 6 Participants |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SCD related SAEs | 3 Participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SCD related SAEs | 9 Participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Non-SCD related TEAEs | 20 Participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SCD related TEAEs | 14 Participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Non-SCD related SAEs | 12 Participants |
Secondary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Plasma
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for plasma and lambdaz is the elimination rate constant.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Plasma | 101000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 20.51 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Plasma | 150000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 38.01 |
Secondary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in RBC
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in RBC | 5550000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 24.31 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in RBC | 9070000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 47.47 |
Secondary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Plasma
AUC0-last was calculated using the linear/log trapezoid rule.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Plasma | 104000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 20.85 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Plasma | 148000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 38.69 |
Secondary
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in RBC
AUC0-last was calculated using the linear/log trapezoid rule.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in RBC | 6070000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 28.69 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in RBC | 8950000 Hours*nanogram per milliliter | Geometric Coefficient of Variation 47.05 |
Secondary
Part A: Maximum Concentration (Cmax) of Voxelotor in Plasma
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Plasma | 1880 Nanogram per milliliter | Geometric Coefficient of Variation 32.49 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Plasma | 3390 Nanogram per milliliter | Geometric Coefficient of Variation 37.82 |
Secondary
Part A: Maximum Concentration (Cmax) of Voxelotor in Red Blood Cells (RBC)
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Red Blood Cells (RBC) | 91500 Nanogram per milliliter | Geometric Coefficient of Variation 33.17 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Maximum Concentration (Cmax) of Voxelotor in Red Blood Cells (RBC) | 168000 Nanogram per milliliter | Geometric Coefficient of Variation 35.56 |
Secondary
Part A: Percentage Hemoglobin (Hb) Occupancy
Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100.
Time frame: 15 days
Population: Data was not collected as the model for Hb occupancy within RBCs was not developed for single dose administration (Part A). The model used to determine % Hb Occupancy was constructed via populational PK modelling and required data from multiple dose administration, thus cannot be applied to estimate the % Hb Occupancy for single doses.
Secondary
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Plasma
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Plasma | 46.4 Hours | Geometric Coefficient of Variation 6.4 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Plasma | 40.7 Hours | Geometric Coefficient of Variation 31.48 |
Secondary
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in RBC
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in RBC | 28.8 Hours | Geometric Coefficient of Variation 12.89 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in RBC | 27.3 Hours | Geometric Coefficient of Variation 30.95 |
Secondary
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Whole Blood
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Whole Blood | 31.9 Hours | Geometric Coefficient of Variation 18.76 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Whole Blood | 28.5 Hours | Geometric Coefficient of Variation 26.18 |
Secondary
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Plasma
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Plasma | 2.83 Hours |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Plasma | 2.83 Hours |
Secondary
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in RBC
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in RBC | 9.00 Hours |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in RBC | 8.75 Hours |
Secondary
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Whole Blood
Time frame: pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Population: PK population comprised of all participants who received any amount of study drug and who provided PK data from at least one post-dose sample in plasma.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Whole Blood | 24.2 Hours |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Whole Blood | 8.73 Hours |
Secondary
Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood
Accumulation ratio was calculated as ratio of area under the concentration-time curve from time 0 to 24 hours (AUC0-24) at steady-state (Day 28) to AUC0-24 on Day 1.
Time frame: Day 1 (0 to 24 hours post-dose) and Day 28 (0 to 24 hours post-dose)
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood | Rac, plasma | 2.57 Ratio | Geometric Coefficient of Variation 29 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood | Rac, whole blood | 2.46 Ratio | Geometric Coefficient of Variation 27 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood | Rac, plasma | 2.62 Ratio | Geometric Coefficient of Variation 33 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood | Rac, whole blood | 2.47 Ratio | Geometric Coefficient of Variation 30 |
Secondary
Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.
Time frame: Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, plasma | 113 Hours*microgram per milliliter | Geometric Coefficient of Variation 46 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, whole blood | 2090 Hours*microgram per milliliter | Geometric Coefficient of Variation 43 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, plasma | 195 Hours*microgram per milliliter | Geometric Coefficient of Variation 40 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, whole blood | 3290 Hours*microgram per milliliter | Geometric Coefficient of Variation 36 |
Secondary
Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow
Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported.
Time frame: Baseline, Weeks 12 and 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow | Week 12 | 0.9 Centimeter per second | Standard Deviation 16.48 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow | Week 24 | -2.1 Centimeter per second | Standard Deviation 14.03 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow | Week 12 | -0.1 Centimeter per second | Standard Deviation 9.34 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow | Week 24 | 1.7 Centimeter per second | Standard Deviation 14.26 |
Secondary
Part B: Change From Baseline to Week 21 to 24 in the Sickle Cell Disease Severity Measure (SCDSM) Total Symptom Score (TSS)
The SCDSM was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale with a range of 0 (strongly disagree) to 4 (strongly agree) that was completed daily using a handheld electronic device by the participants. TSS was calculated as the sum of the 9-item questionnaire scores scaled to a 100-point scale with a range of 0 (no symptoms) to 100 (most severe symptoms). Baseline TSS was the average of the non-missing score during the Screening period. The average of change from baseline in SCDSM TSS score for the 4-week period (Week 21 to 24) is reported.
Time frame: Baseline, Weeks 21 to 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 21 to 24 in the Sickle Cell Disease Severity Measure (SCDSM) Total Symptom Score (TSS) | 6.4 Units on a scale | Standard Deviation 17.98 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Change From Baseline to Week 21 to 24 in the Sickle Cell Disease Severity Measure (SCDSM) Total Symptom Score (TSS) | -10.7 Units on a scale | Standard Deviation 18.7 |
Secondary
Part B: Cmax of Voxelotor in Whole Blood and Plasma
Time frame: Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Cmax of Voxelotor in Whole Blood and Plasma | Cmax, plasma | 5.64 Microgram per milliliter | Geometric Coefficient of Variation 41 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Cmax of Voxelotor in Whole Blood and Plasma | Cmax, whole blood | 102 Microgram per milliliter | Geometric Coefficient of Variation 38 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Cmax of Voxelotor in Whole Blood and Plasma | Cmax, plasma | 9.81 Microgram per milliliter | Geometric Coefficient of Variation 37 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Cmax of Voxelotor in Whole Blood and Plasma | Cmax, whole blood | 159 Microgram per milliliter | Geometric Coefficient of Variation 32 |
Secondary
Part B: Percentage Hemoglobin Occupancy
Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100.
Time frame: Day 28
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percentage Hemoglobin Occupancy | 19.4 Percentage of bound hemoglobin | Geometric Coefficient of Variation 34 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percentage Hemoglobin Occupancy | 29.5 Percentage of bound hemoglobin | Geometric Coefficient of Variation 27 |
Secondary
Part B: Percentage of Days With SCD Symptom Exacerbation During the First 24 Weeks of Treatment
SCD symptoms were measured using the Patient Reported Outcome (PRO), Sickle Cell Disease Severity Measure (SCDSM) which was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale that was completed daily using a handheld electronic device by the participants.
Time frame: From Day 1 up to 24 weeks
Population: The variable represents a derivation from a new instrument developed by the sponsor specifically for this clinical program. Due to challenges in the validation of Percentage of Days With SCD Symptom Exacerbation from the instrument, specifically with the impact of missing data, the construct of this variable was not possible. A decision not to analyze this variable was documented in the statistical analysis plan.
Secondary
Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin
Time frame: Baseline, Weeks 12 and 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin | Week 12 | -32.1 Percent change | Standard Deviation 31.98 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin | Week 24 | -37.5 Percent change | Standard Deviation 29.07 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin | Week 12 | -29.9 Percent change | Standard Deviation 33.59 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin | Week 24 | -32.1 Percent change | Standard Deviation 31.53 |
Secondary
Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH)
Time frame: Baseline, Weeks 12 and 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH) | Week 12 | -6.3 Percent change | Standard Deviation 21.08 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH) | Week 24 | -6.3 Percent change | Standard Deviation 22.47 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH) | Week 12 | -1.7 Percent change | Standard Deviation 32.78 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH) | Week 24 | -1.9 Percent change | Standard Deviation 14.59 |
Secondary
Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes
Time frame: Baseline, Weeks 12 and 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes | Week 12 | -8.7 Percent change | Standard Deviation 36.46 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes | Week 24 | -14.1 Percent change | Standard Deviation 34.06 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes | Week 12 | -3.5 Percent change | Standard Deviation 42.96 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes | Week 24 | 1.5 Percent change | Standard Deviation 43.18 |
Secondary
Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood | T1/2, plasma | 33 Hours | Geometric Coefficient of Variation 41 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood | T1/2, whole blood | 31.1 Hours | Geometric Coefficient of Variation 39 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood | T1/2, plasma | 33.9 Hours | Geometric Coefficient of Variation 44 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood | T1/2, whole blood | 31.4 Hours | Geometric Coefficient of Variation 41 |
Secondary
Part C: Annualized Incidence Rate of Stroke Events
Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.
Time frame: Up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Annualized Incidence Rate of Stroke Events | 0.000 Stroke events per person year |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Annualized Incidence Rate of Stroke Events | 0.000 Stroke events per person year |
Secondary
Part C: Annualized Incidence Rate of Vaso-occlusive Crisis (VOC) Events
VOC events included preferred terms of sickle cell anaemia with crisis, acute chest syndrome, pneumonia necrotising and pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.
Time frame: Up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Annualized Incidence Rate of Vaso-occlusive Crisis (VOC) Events | 1.246 VOC events per person year |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Annualized Incidence Rate of Vaso-occlusive Crisis (VOC) Events | 2.250 VOC events per person year |
Secondary
Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.
Time frame: Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, plasma | 160 Hours*microgram per milliliter | Geometric Coefficient of Variation 72 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, whole blood | 2660 Hours*microgram per milliliter | Geometric Coefficient of Variation 64 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, plasma | 184 Hours*microgram per milliliter | Geometric Coefficient of Variation 44 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma | AUC0-inf, whole blood | 2880 Hours*microgram per milliliter | Geometric Coefficient of Variation 41 |
Secondary
Part C: Change From Baseline to Week 24 in Cerebral Blood Flow
Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported.
Time frame: Baseline, Week 24
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Change From Baseline to Week 24 in Cerebral Blood Flow | -3.2 Centimeter per second | Standard Deviation 15.69 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Change From Baseline to Week 24 in Cerebral Blood Flow | -11.8 Centimeter per second | Standard Deviation 18.82 |
Secondary
Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 24 | 1.0 Grams per deciliter | Standard Deviation 1.16 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 48 | 0.7 Grams per deciliter | Standard Deviation 1.15 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 24 | 0.8 Grams per deciliter | Standard Deviation 1.14 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 48 | -0.1 Grams per deciliter | Standard Deviation 0.2 |
Secondary
Part C: Cmax of Voxelotor for Plasma and Whole Blood
Time frame: Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, plasma | 7.83 Microgram per milliliter | Geometric Coefficient of Variation 61 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, whole blood | 127 Microgram per milliliter | Geometric Coefficient of Variation 52 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, plasma | 9.04 Microgram per milliliter | Geometric Coefficient of Variation 43 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, whole blood | 137 Microgram per milliliter | Geometric Coefficient of Variation 38 |
Secondary
Part C: Percentage Hemoglobin Occupancy of Voxelotor
Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100.
Time frame: Day 28
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percentage Hemoglobin Occupancy of Voxelotor | 24.7 Percentage of bound hemoglobin | Geometric Coefficient of Variation 47 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percentage Hemoglobin Occupancy of Voxelotor | 27.7 Percentage of bound hemoglobin | Geometric Coefficient of Variation 30 |
Secondary
Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48
Normal TCD flow velocity was considered as \< 170 centimeter per second (cm/sec) by non-imagining TCD or \< 155 cm/sec by imaging transcranial Doppler (TCDi). Percentage of participants with normal TCD flow velocity at Week 48 by Baseline TCD group (i.e. Baseline normal TCD \[\<170 cm/sec\] and Baseline conditional TCD \[\>=170 cm/sec\] is reported.
Time frame: Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. All participants reported under, 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for each row. Here, 'Number Analyzed ' signifies number of participants evaluable for each row.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48 | Baseline normal | 96.3 Percentage of participants |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48 | Baseline conditional | 42.9 Percentage of participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48 | Baseline normal | 100 Percentage of participants |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48 | Baseline conditional | 100 Percentage of participants |
Secondary
Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 24 | -36.9 Percent change | Standard Deviation 26.55 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 48 | -26.6 Percent change | Standard Deviation 37.05 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 24 | -45.7 Percent change | Standard Deviation 24.93 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 48 | -33.0 Percent change | Standard Deviation 36.76 |
Secondary
Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 24 | -5.1 Percent change | Standard Deviation 21.95 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 48 | -1.8 Percent change | Standard Deviation 23.8 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 24 | -22.4 Percent change | Standard Deviation 22.08 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 48 | 3.9 Percent change | Standard Deviation 8.91 |
Secondary
Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes | Week 24 | -4.76 Percent change | Standard Deviation 42.999 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes | Week 48 | -0.33 Percent change | Standard Deviation 46.353 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes | Week 24 | -1.17 Percent change | Standard Deviation 31.595 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes | Week 48 | 2.94 Percent change | Standard Deviation 38.295 |
Secondary
Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma | T1/2, plasma | 41.6 Hours | Geometric Coefficient of Variation 50 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma | T1/2, whole blood | 37.4 Hours | Geometric Coefficient of Variation 48 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma | T1/2, plasma | 35.6 Hours | Geometric Coefficient of Variation 28 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma | T1/2, whole blood | 32.7 Hours | Geometric Coefficient of Variation 25 |
Secondary
Part C: Time to Initial Hemoglobin Response
Time to initial Hb response was defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb \> 1 gram per deciliter (g/dL).
Time frame: From first dose of study treatment (Day 1) up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part C: Time to Initial Hemoglobin Response | 4.9 Weeks | Standard Deviation 5.51 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part C: Time to Initial Hemoglobin Response | 5.6 Weeks | Standard Deviation 4.9 |
Secondary
Part D: Annualized Incidence Rate of Stroke Events
Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.
Time frame: Up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Annualized Incidence Rate of Stroke Events | 0.000 Stroke events per person year |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Annualized Incidence Rate of Stroke Events | 0.000 Stroke events per person year |
Secondary
Part D: Annualized Incidence Rate of VOC Events
VOC events included preferred terms of 'Sickle cell anemia with crisis', 'Acute chest syndrome', 'Pneumonia necrotising,' and 'Pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.
Time frame: Up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Annualized Incidence Rate of VOC Events | 1.473 VOC events per person year |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Annualized Incidence Rate of VOC Events | 1.399 VOC events per person year |
Secondary
Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood
AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.
Time frame: Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood | AUC0-inf, plasma | 89.9 Hours*microgram per milliliter | Geometric Coefficient of Variation 110 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood | AUC0-inf, whole blood | 1600 Hours*microgram per milliliter | Geometric Coefficient of Variation 120 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood | AUC0-inf, plasma | 186 Hours*microgram per milliliter | Geometric Coefficient of Variation 38 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood | AUC0-inf, whole blood | 3040 Hours*microgram per milliliter | Geometric Coefficient of Variation 36 |
Secondary
Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 48 | 0.5 Grams per deciliter | Standard Deviation 1.53 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 24 | 0.4 Grams per deciliter | Standard Deviation 2.03 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 24 | 0.6 Grams per deciliter | Standard Deviation 1.02 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level | Week 48 | 0.7 Grams per deciliter | Standard Deviation 1.45 |
Secondary
Part D: Cmax of Voxelotor for Plasma and Whole Blood
Time frame: Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, plasma | 5.01 Microgram per milliliter | Geometric Coefficient of Variation 73 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, whole blood | 87.2 Microgram per milliliter | Geometric Coefficient of Variation 74 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, plasma | 9.45 Microgram per milliliter | Geometric Coefficient of Variation 34 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Cmax of Voxelotor for Plasma and Whole Blood | Cmax, whole blood | 149 Microgram per milliliter | Geometric Coefficient of Variation 30 |
Secondary
Part D: Percentage Hemoglobin Occupancy
Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: (\[Concentration of voxelotor in whole blood- {1-hematocrit}\]\*\[Concentration of voxelotor in plasma/hematocrit\])/5000\*100.
Time frame: Day 28
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percentage Hemoglobin Occupancy | 17.5 Percentage of bound hemoglobin | Geometric Coefficient of Variation 60 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percentage Hemoglobin Occupancy | 28.9 Percentage of bound hemoglobin | Geometric Coefficient of Variation 26 |
Secondary
Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 24 | -14.4 Percent change | Standard Deviation 28.11 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 48 | 4.4 Percent change | Standard Deviation 42.05 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 24 | -24.5 Percent change | Standard Deviation 24.5 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin | Week 48 | -24.5 Percent change | Standard Deviation 21.97 |
Secondary
Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 24 | 27.6 Percent change | Standard Deviation 56.46 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 48 | 26.3 Percent change | Standard Deviation 43.98 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 24 | -0.4 Percent change | Standard Deviation 31.53 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH | Week 48 | 7.4 Percent change | Standard Deviation 45.94 |
Secondary
Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count
Time frame: Baseline, Weeks 24 and 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count | Week 24 | -3.6 Percent change | Standard Deviation 28.64 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count | Week 48 | -11.5 Percent change | Standard Deviation 31.19 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count | Week 24 | 3.8 Percent change | Standard Deviation 31.88 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count | Week 48 | -0.7 Percent change | Standard Deviation 29.7 |
Secondary
Part D: T1/2 of Voxelotor for Plasma and Whole Blood
T1/2 was the time measured for the drug concentration to decrease by one half.
Time frame: Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Population: PK population comprised of participants who received at least one dose of voxelotor and had at least 1 measurable voxelotor concentration observation in plasma or whole blood with associated sampling time and dosing information. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: T1/2 of Voxelotor for Plasma and Whole Blood | T1/2, plasma | 24.1 Hours | Geometric Coefficient of Variation 70 |
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: T1/2 of Voxelotor for Plasma and Whole Blood | T1/2, whole blood | 21.7 Hours | Geometric Coefficient of Variation 82 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: T1/2 of Voxelotor for Plasma and Whole Blood | T1/2, plasma | 36.1 Hours | Geometric Coefficient of Variation 40 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: T1/2 of Voxelotor for Plasma and Whole Blood | T1/2, whole blood | 32.7 Hours | Geometric Coefficient of Variation 38 |
Secondary
Part D: Time to Initial Hemoglobin Response
Time to initial Hb response, defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb \> 1 g/dL.
Time frame: From first dose of study treatment (Day 1) up to Week 48
Population: Efficacy-Evaluable Population comprised of all participants who received any amount of study drug. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Participants Aged 12 to 17 Years: Voxelotor 600 mg | Part D: Time to Initial Hemoglobin Response | 8.0 Weeks | Standard Deviation 7.6 |
| Part A: Participants Aged 6 to 11 Years: Voxelotor 600 mg | Part D: Time to Initial Hemoglobin Response | 4.7 Weeks | Standard Deviation 8.8 |