Trial Outcomes & Findings for Pharmacokinetics of Oral Hydroxyurea Solution (NCT NCT03763656)
NCT ID: NCT03763656
Last Updated: 2024-10-28
Results Overview
Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Results posted on
2024-10-28
Participant Flow
Participants were recruited from one Jamaican sickle cell clinic (n=12) and five UK hospitals (n=20). The first participant was enrolled on 03 Jan 2019 and the last participant was enrolled on 16 Dec 2020.
33 participants enrolled met the inclusion criteria; 32 initiated treatment with open label Hydroxyurea and one participant discontinued pre-treatment.
Participant milestones
| Measure |
Oral Hydroxyurea
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
Pre-treatment Discontinuation
|
1
|
|
Overall Study
Safety Population
|
32
|
|
Overall Study
Age Group (6 Months - 1.99 Years)
|
6
|
|
Overall Study
Discontinuations From Age Group (6 Months - 1.99 Years)
|
3
|
|
Overall Study
Completed From Age Group (6 Months - 1.99 Years)
|
3
|
|
Overall Study
Age Group (2 - 5.99 Years)
|
16
|
|
Overall Study
Discontinuations From Age Group (2 - 5.99 Years)
|
2
|
|
Overall Study
Completions From Age Group (2 - 5.99 Years)
|
14
|
|
Overall Study
Age Group (6 - 17.99 Years)
|
10
|
|
Overall Study
Discontinuations From Age Group (6 - 17.99 Years)
|
3
|
|
Overall Study
Completions From Age Group (6 - 17.99 Years)
|
7
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Oral Hydroxyurea
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Withdrawal by Subject
|
7
|
Baseline Characteristics
Overall demographic population of 33 participants.
Baseline characteristics by cohort
| Measure |
Oral Hydroxyurea
n=33 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 - 17.99 years) · Unknown or Not Reported
|
0 Participants
n=11 Participants • Overall demographic population of 33 participants.
|
|
Race/Ethnicity, Customized
Race (Overall) · American Indian or Alaska Native
|
0 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Overall) · Asian
|
0 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Age, Customized
Age by Category · Age Group (6 months - 1.99 years)
|
6 Participants
n=33 Participants
|
|
Age, Customized
Age by Category · Age Group (2 - 5.99 years)
|
16 Participants
n=33 Participants
|
|
Age, Customized
Age by Category · Age Group (6 - 17.99 years)
|
11 Participants
n=33 Participants
|
|
Sex: Female, Male
Sex: Female, Male (Overall) · Female
|
17 Participants
n=33 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Overall) · Male
|
16 Participants
n=33 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 6 months - 1.99 years) · Female
|
5 Participants
n=6 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 6 months - 1.99 years) · Male
|
1 Participants
n=6 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 2 - 5.99 years) · Female
|
5 Participants
n=16 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 2 - 5.99 years) · Male
|
11 Participants
n=16 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 6 - 17.99 years) · Female
|
7 Participants
n=11 Participants • Overall demographic population of 33 participants.
|
|
Sex: Female, Male
Sex: Female, Male (Age group 6 - 17.99 years) · Male
|
4 Participants
n=11 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity Overall · Hispanic or Latino
|
0 Participants
n=33 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity Overall · Not Hispanic or Latino
|
33 Participants
n=33 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity Overall · Unknown or Not Reported
|
0 Participants
n=33 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 months - 1.99 years) · Hispanic or Latino
|
0 Participants
n=6 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 months - 1.99 years) · Not Hispanic or Latino
|
6 Participants
n=6 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 months - 1.99 years) · Unknown or Not Reported
|
0 Participants
n=6 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 2 - 5.99 years) · Hispanic or Latino
|
0 Participants
n=16 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 2 - 5.99 years) · Not Hispanic or Latino
|
16 Participants
n=16 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 2 - 5.99 years) · Unknown or Not Reported
|
0 Participants
n=16 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 - 17.99 years) · Hispanic or Latino
|
0 Participants
n=11 Participants • Overall demographic population of 33 participants.
|
|
Ethnicity (NIH/OMB)
Ethnicity (Age Group 6 - 17.99 years) · Not Hispanic or Latino
|
11 Participants
n=11 Participants • Overall demographic population of 33 participants.
|
|
Race/Ethnicity, Customized
Race (Overall) · Black or African American
|
31 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Overall) · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Overall) · White
|
0 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Overall) · Other (Specify): [sic] Caribbean
|
1 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Overall) · Other (Specify): Black British
|
1 Participants
n=33 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · American Indian or Alaska Native
|
0 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · Asian
|
0 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · Black or African American
|
5 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · White
|
0 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · Other (Specify): [sic] Caribbean
|
1 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 months - 1.99 years) · Other (Specify): Black British
|
0 Participants
n=6 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · American Indian or Alaska Native
|
0 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · Asian
|
0 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · Black or African American
|
15 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · White
|
0 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · Other (Specify): [sic] Caribbean
|
0 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 2 - 5.99 years) · Other (Specify): Black British
|
1 Participants
n=16 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · American Indian or Alaska Native
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · Asian
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · Black or African American
|
11 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · White
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · Other (Specify): [sic] Caribbean
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Race/Ethnicity, Customized
Race (Age Group 6 - 17.99 years) · Other (Specify): Black British
|
0 Participants
n=11 Participants • Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" \[sic\] and "Black British".
|
|
Region of Enrollment
United Kingdom
|
20 participants
n=33 Participants
|
|
Region of Enrollment
Jamaica
|
13 participants
n=33 Participants
|
|
SCA Type
SCA Type (Overall) · HbSS
|
32 Participants
n=33 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Overall) · HbSbeta0
|
1 Participants
n=33 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 6 months - 1.99 years) · HbSS
|
6 Participants
n=6 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 6 months - 1.99 years) · HbSbeta0
|
0 Participants
n=6 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 2 - 5.99 years) · HbSS
|
15 Participants
n=16 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 2 - 5.99 years) · HbSbeta0
|
1 Participants
n=16 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 6 - 17.99 years) · HbSS
|
11 Participants
n=11 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
SCA Type
SCA Type (Age Group 6 - 17.99 years) · HbSbeta0
|
0 Participants
n=11 Participants • SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes.
|
|
Height
Height (cm) (Overall)
|
109.26 cm
STANDARD_DEVIATION 26.038 • n=31 Participants • Overall safety population of 32 participants, data available at screening for 31 participants. Height or length was unobtainable for 1 participant who was under the age of 2 years (Age group 6 months - 1.99 years).
|
|
Height
Height (cm) Age Group (6 months - 1.99 years)
|
79.40 cm
STANDARD_DEVIATION 5.237 • n=5 Participants • Overall safety population of 32 participants, data available at screening for 31 participants. Height or length was unobtainable for 1 participant who was under the age of 2 years (Age group 6 months - 1.99 years).
|
|
Height
Height (cm) Age Group (2 - 5.99 years)
|
98.08 cm
STANDARD_DEVIATION 6.947 • n=16 Participants • Overall safety population of 32 participants, data available at screening for 31 participants. Height or length was unobtainable for 1 participant who was under the age of 2 years (Age group 6 months - 1.99 years).
|
|
Height
Height (cm) Age Group (6 - 17.99 years)
|
142.09 cm
STANDARD_DEVIATION 15.872 • n=10 Participants • Overall safety population of 32 participants, data available at screening for 31 participants. Height or length was unobtainable for 1 participant who was under the age of 2 years (Age group 6 months - 1.99 years).
|
|
Weight
Weight (kg) Overall
|
19.63 kg
STANDARD_DEVIATION 10.955 • n=32 Participants • Overall safety population of 32 participants.
|
|
Weight
Weight (kg) Age Group (6 months - 1.99 years)
|
11.18 kg
STANDARD_DEVIATION 1.017 • n=6 Participants • Overall safety population of 32 participants.
|
|
Weight
Weight (kg) Age Group (2 - 5.99 years)
|
14.74 kg
STANDARD_DEVIATION 2.092 • n=16 Participants • Overall safety population of 32 participants.
|
|
Weight
Weight (kg) Age Group (6 - 17.99 years)
|
32.52 kg
STANDARD_DEVIATION 11.441 • n=10 Participants • Overall safety population of 32 participants.
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: Clearance value for patient of 15.05 kg
Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug).
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Clearance (CL/F)
|
3.61 L/hr
Interval 3.29 to 3.92
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: Volume of distribution for central and peripheral compartments for patient of 15.05 kg
Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug).
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Volume of Distribution (V/F)
|
11.4 L
Interval 9.52 to 13.2
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: PK population = 32 participants, who have received at least one dose at 15 mg/kg and have at least one sample of PK plasma above the lower limit of quantification
Mean Tmax (h) pharmacokinetic parameter derived using the final population PK model.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Time to Maximum Concentration (Tmax)
Tmax (Overall)
|
1.253 hours
Standard Deviation 0.412
|
|
Time to Maximum Concentration (Tmax)
Tmax (Age Group 6 months - 1.99 years)
|
1.265 hours
Standard Deviation 0.322
|
|
Time to Maximum Concentration (Tmax)
Tmax (Age Group 2 - 5.99 years)
|
1.238 hours
Standard Deviation 0.455
|
|
Time to Maximum Concentration (Tmax)
Tmax (Age Group 6 - 17.99 years)
|
1.269 hours
Standard Deviation 0.423
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: PK population: n=32 safety population, having received at least one dose of study drug at 15mg/kg and one sample of PK plasma above the lower limit of quantification.
Mean Cmax (ug/mL) pharmacokinetic parameter derived using the final population PK model.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Maximum Plasma Concentration Cmax (ug/mL)
Cmax (Overall)
|
13.124 ug/mL
Standard Deviation 1.742
|
|
Maximum Plasma Concentration Cmax (ug/mL)
Cmax (Age Group 6 months - 1.99 years)
|
12.807 ug/mL
Standard Deviation 1.399
|
|
Maximum Plasma Concentration Cmax (ug/mL)
Cmax (Age Group 2 - 5.99 years)
|
13.068 ug/mL
Standard Deviation 1.939
|
|
Maximum Plasma Concentration Cmax (ug/mL)
Cmax (Age Group 6 - 17.99 years)
|
13.404 ug/mL
Standard Deviation 1.714
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: PK population = 32 participants receiving at least one dose of 15mg/kg hydroxyurea and have at least one PK plasma sample above lower limit of quantification.
Mean AUC 0-Infinity (hr\*ug/mL) pharmacokinetic parameters derived using the final population PK model.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Area Under Plasma Concentration Time Curve (AUC 0-Inf)
AUC Infinity (Overall)
|
64.721 hr*ug/mL
Standard Deviation 9.339
|
|
Area Under Plasma Concentration Time Curve (AUC 0-Inf)
AUC Infinity (Age Group 6 months - 1.99 years)
|
62.537 hr*ug/mL
Standard Deviation 9.016
|
|
Area Under Plasma Concentration Time Curve (AUC 0-Inf)
AUC Infinity (Age Group 2 - 5.99 years)
|
62.899 hr*ug/mL
Standard Deviation 7.373
|
|
Area Under Plasma Concentration Time Curve (AUC 0-Inf)
AUC Infinity (Age Group 6 - 17.99 years)
|
68.948 hr*ug/mL
Standard Deviation 11.649
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)Population: PK Population n=32 where all subjects received at least one dose of 15 mg/kg hydroxyurea and have at least one sample of PK plasma above the lower limit of quantification.
Mean Terminal Half-life (hours) pharmacokinetic parameter derived using the final population PK model.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Terminal Half-life (Hours)
Terminal Half-life (Overall)
|
3.880 hours
Standard Deviation 0.3004
|
|
Terminal Half-life (Hours)
Terminal Half-life (Age Group 6 months - 1.99 years)
|
4.107 hours
Standard Deviation 0.187
|
|
Terminal Half-life (Hours)
Terminal Half-life (Age Group 2 - 5.99 years)
|
3.949 hours
Standard Deviation 0.257
|
|
Terminal Half-life (Hours)
Terminal Half-life (Age 6 - 17.99 years)
|
3.634 hours
Standard Deviation 0.268
|
SECONDARY outcome
Timeframe: Screening Up to Week 64Population: Safety population n=32. Overall 339 AEs in 31 participants recorded. 7 adverse events included in this list of 339 were defined as 'Serious' as per the protocol definition (i.e. SCA related and \>7days hospitalisation). A separate SAE report was made at that time with a clearly defined start and end date to be able to denote a resolution to the 'seriousness' criteria as this is an ongoing chronic condition.
Incidence of Adverse events during the course of the trial from screening to final follow up phone call at Week 64. Relatedness refers to 'at least possibly related to the IMP', with severity/toxicity assessed using the CTCAE Toxicity Grade and seriousness based on the standard definition for SAE in accordance with GCP. With the exception of SCA related events, requiring \>7day hospitalisation, or extension of hospitalisation before being reported as an SAE due to their frequency within the disease population. All other non-SCA related SAEs were reportable.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Adverse Events
Any Adverse Events (Overall)
|
339 events
|
|
Adverse Events
Treatment Emergent Adverse Events (TEAEs) Overall
|
339 events
|
|
Adverse Events
Serious AEs
|
7 events
|
|
Adverse Events
Grade >or=3 TEAEs
|
19 events
|
|
Adverse Events
Related TEAEs
|
28 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: SCA with Crisis
|
53 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: Upper Respiratory Tract Infection
|
43 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: Pyrexia
|
16 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: Cough
|
7 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: Vomiting
|
6 events
|
|
Adverse Events
Commonly occurring unrelated TEAE: Abdominal Pain
|
7 events
|
|
Adverse Events
Commonly occurring possibly related TEAE: Neutropenia/ANC Count Decreased
|
4 events
|
|
Adverse Events
Commonly occurring possibly related TEAE: Thrombocytopenia/Platelet Count Decreased
|
6 events
|
SECONDARY outcome
Timeframe: Baseline and Week 60 (or final visit); max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Safety review for haematological toxicity (mild myelosuppression target: 1-3x10\^9/L)
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Absolute Neutrophil Count (ANC)
Screening (Overall)
|
4.90 x10^9 neutrophils/L
Standard Deviation 1.825
|
|
Absolute Neutrophil Count (ANC)
Screening (6 months - 1.99 years)
|
4.30 x10^9 neutrophils/L
Standard Deviation 1.608
|
|
Absolute Neutrophil Count (ANC)
Screening (2 - 5.99 years)
|
5.38 x10^9 neutrophils/L
Standard Deviation 2.087
|
|
Absolute Neutrophil Count (ANC)
Screening (6 - 17.99 years)
|
4.43 x10^9 neutrophils/L
Standard Deviation 1.354
|
|
Absolute Neutrophil Count (ANC)
Final Visit (Overall)
|
2.70 x10^9 neutrophils/L
Standard Deviation 1.033
|
|
Absolute Neutrophil Count (ANC)
Final Visit (6 months - 1.99 years)
|
2.27 x10^9 neutrophils/L
Standard Deviation 0.671
|
|
Absolute Neutrophil Count (ANC)
Final Visit (2 - 5.99 years)
|
2.46 x10^9 neutrophils/L
Standard Deviation 0.837
|
|
Absolute Neutrophil Count (ANC)
Final Visit (6 - 17.99 years)
|
3.48 x10^9 neutrophils/L
Standard Deviation 1.255
|
SECONDARY outcome
Timeframe: Baseline to Week 60 or Final Visit; max 15 months on treatmentPopulation: Leukocytes Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
White Blood Cell Count (Leukocytes)
Screening (Overall)
|
13.01 10^9 leukocytes/L
Standard Deviation 3.514
|
|
White Blood Cell Count (Leukocytes)
Screening (6 months - 1.99 years)
|
12.24 10^9 leukocytes/L
Standard Deviation 2.019
|
|
White Blood Cell Count (Leukocytes)
Screening (2 - 5.99 years)
|
14.59 10^9 leukocytes/L
Standard Deviation 3.856
|
|
White Blood Cell Count (Leukocytes)
Screening (6 - 17.99 years)
|
10.88 10^9 leukocytes/L
Standard Deviation 2.188
|
|
White Blood Cell Count (Leukocytes)
Final Visit (Overall)
|
7.48 10^9 leukocytes/L
Standard Deviation 2.286
|
|
White Blood Cell Count (Leukocytes)
Final Visit (6 months - 1.99 years)
|
7.90 10^9 leukocytes/L
Standard Deviation 2.466
|
|
White Blood Cell Count (Leukocytes)
Final Visit (2 - 5.99 years)
|
6.83 10^9 leukocytes/L
Standard Deviation 2.244
|
|
White Blood Cell Count (Leukocytes)
Final Visit (6 - 17.99 years)
|
8.41 10^9 leukocytes/L
Standard Deviation 2.108
|
SECONDARY outcome
Timeframe: Baseline to Week 60 (or Final Visit), max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Platelets
Screening (Overall)
|
409.06 10^9 platelets/L
Standard Deviation 131.542
|
|
Platelets
Screening (6 months - 1.99 years)
|
383.80 10^9 platelets/L
Standard Deviation 52.756
|
|
Platelets
Screening (2 - 5.99 years)
|
381.31 10^9 platelets/L
Standard Deviation 104.305
|
|
Platelets
Screening (6 - 17.99 years)
|
466.10 10^9 platelets/L
Standard Deviation 181.577
|
|
Platelets
Final Visit (Overall)
|
315.10 10^9 platelets/L
Standard Deviation 134.057
|
|
Platelets
Final Visit (6 months - 1.99 years)
|
333.67 10^9 platelets/L
Standard Deviation 98.699
|
|
Platelets
Final Visit (2 - 5.99 years)
|
258.00 10^9 platelets/L
Standard Deviation 141.782
|
|
Platelets
Final Visit (6 - 17.99 years)
|
408.25 10^9 platelets/L
Standard Deviation 86.742
|
SECONDARY outcome
Timeframe: Baseline to Week 60 (or Final Visit), max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Mean Corpuscular Hemoglobin (MCH)
Screening (Overall)
|
27.57 pg
Standard Deviation 3.741
|
|
Mean Corpuscular Hemoglobin (MCH)
Screening (6 months - 1.99 years)
|
23.80 pg
Standard Deviation 3.291
|
|
Mean Corpuscular Hemoglobin (MCH)
Screening (2 - 5.99 years)
|
28.36 pg
Standard Deviation 4.665
|
|
Mean Corpuscular Hemoglobin (MCH)
Screening (6 - 17.99 years)
|
28.53 pg
Standard Deviation 1.015
|
|
Mean Corpuscular Hemoglobin (MCH)
Final Visit (Overall)
|
33.36 pg
Standard Deviation 4.590
|
|
Mean Corpuscular Hemoglobin (MCH)
Final Visit (6 months - 1.99 years)
|
28.95 pg
Standard Deviation 8.126
|
|
Mean Corpuscular Hemoglobin (MCH)
Final Visit (2 - 5.99 years)
|
34.02 pg
Standard Deviation 3.971
|
|
Mean Corpuscular Hemoglobin (MCH)
Final Visit (6 - 17.99 years)
|
34.31 pg
Standard Deviation 2.307
|
SECONDARY outcome
Timeframe: Up to Week 60Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Hematocrit
Screening (Overall)
|
25.02 % by volume of red blood cells in blood
Standard Deviation 4.4
|
|
Hematocrit
Screening (6 months - 1.99 years)
|
30.60 % by volume of red blood cells in blood
Standard Deviation 3.161
|
|
Hematocrit
Screening (2 - 5.99 years)
|
23.24 % by volume of red blood cells in blood
Standard Deviation 3.378
|
|
Hematocrit
Screening (6 - 17.99 years)
|
24.30 % by volume of red blood cells in blood
Standard Deviation 4.081
|
|
Hematocrit
Final Visit (Overall)
|
27.74 % by volume of red blood cells in blood
Standard Deviation 3.995
|
|
Hematocrit
Final Visit (6 months - 1.99 years)
|
30.38 % by volume of red blood cells in blood
Standard Deviation 3.035
|
|
Hematocrit
Final Visit (2 - 5.99 years)
|
28.45 % by volume of red blood cells in blood
Standard Deviation 4.001
|
|
Hematocrit
Final Visit (6 - 17.99 years)
|
25.10 % by volume of red blood cells in blood
Standard Deviation 3.208
|
SECONDARY outcome
Timeframe: Up to Week 60Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Bilirubin
Screening (Overall)
|
37.43 umol/L
Standard Deviation 19.649
|
|
Bilirubin
Screening (6 months - 1.99 years)
|
14.78 umol/L
Standard Deviation 9.763
|
|
Bilirubin
Screening (2 - 5.99 years)
|
39.60 umol/L
Standard Deviation 19.777
|
|
Bilirubin
Screening (6 - 17.99 years)
|
47.53 umol/L
Standard Deviation 12.702
|
|
Bilirubin
Final Visit (Overall)
|
26.12 umol/L
Standard Deviation 16.191
|
|
Bilirubin
Final Visit (6 months - 1.99 years)
|
7.42 umol/L
Standard Deviation 1.941
|
|
Bilirubin
Final Visit (Screening (2 - 5.99 years)
|
26.25 umol/L
Standard Deviation 13.331
|
|
Bilirubin
Final Visit (Screening (6 - 17.99 years)
|
39.89 umol/L
Standard Deviation 13.191
|
SECONDARY outcome
Timeframe: Up to Week 60Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry, including Liver Function Tests (LFTs): Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT)
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Elevation in Liver Function Tests (LFTs)
ALP Screening (Overall)
|
3.55 ukat/L
Standard Deviation 0.846
|
|
Elevation in Liver Function Tests (LFTs)
ALP Screening (6 months - 1.99 years)
|
4.19 ukat/L
Standard Deviation 0.983
|
|
Elevation in Liver Function Tests (LFTs)
ALP Screening (2 - 5.99 years)
|
3.60 ukat/L
Standard Deviation 0.666
|
|
Elevation in Liver Function Tests (LFTs)
ALP Screening (6 - 17.99 years)
|
3.10 ukat/L
Standard Deviation 0.827
|
|
Elevation in Liver Function Tests (LFTs)
ALP Final Visit (Overall)
|
3.57 ukat/L
Standard Deviation 0.858
|
|
Elevation in Liver Function Tests (LFTs)
ALP Final Visit (6 months - 1.99 years)
|
4.06 ukat/L
Standard Deviation 0.820
|
|
Elevation in Liver Function Tests (LFTs)
ALP Final Visit (2 months - 5.99 years)
|
3.41 ukat/L
Standard Deviation 0.578
|
|
Elevation in Liver Function Tests (LFTs)
ALP Final Visit (6 - 17.99 years)
|
3.52 ukat/L
Standard Deviation 1.237
|
|
Elevation in Liver Function Tests (LFTs)
GGT Screening (Overall)
|
0.38 ukat/L
Standard Deviation 0.333
|
|
Elevation in Liver Function Tests (LFTs)
GGT Screening (6 months - 1.99 years)
|
0.16 ukat/L
Standard Deviation 0.034
|
|
Elevation in Liver Function Tests (LFTs)
GGT Screening (2 - 5.99 years)
|
0.32 ukat/L
Standard Deviation 0.231
|
|
Elevation in Liver Function Tests (LFTs)
GGT Screening (6 - 17.99 years)
|
0.62 ukat/L
Standard Deviation 0.437
|
|
Elevation in Liver Function Tests (LFTs)
GGT Final Visit (Overall)
|
0.32 ukat/L
Standard Deviation 0.233
|
|
Elevation in Liver Function Tests (LFTs)
GGT Final Visit (6 months - 1.99 years)
|
0.16 ukat/L
Standard Deviation 0.040
|
|
Elevation in Liver Function Tests (LFTs)
GGT Final Visit (2 - 5.99 years)
|
0.29 ukat/L
Standard Deviation 0.174
|
|
Elevation in Liver Function Tests (LFTs)
GGT Final Visit (6 - 17.99 years)
|
0.49 ukat/L
Standard Deviation 0.316
|
|
Elevation in Liver Function Tests (LFTs)
AST Screening (Overall)
|
0.85 ukat/L
Standard Deviation 0.221
|
|
Elevation in Liver Function Tests (LFTs)
AST Screening (6 months - 1.99 years)
|
0.72 ukat/L
Standard Deviation 0.178
|
|
Elevation in Liver Function Tests (LFTs)
AST Screening (2 - 5.99 years)
|
0.84 ukat/L
Standard Deviation 0.212
|
|
Elevation in Liver Function Tests (LFTs)
AST Screening (6 - 17.99 years)
|
0.92 ukat/L
Standard Deviation 0.244
|
|
Elevation in Liver Function Tests (LFTs)
AST Final Visit (Overallk)
|
0.67 ukat/L
Standard Deviation 0.165
|
|
Elevation in Liver Function Tests (LFTs)
AST Final Visit (6 months - 1.99 years)
|
0.61 ukat/L
Standard Deviation 0.066
|
|
Elevation in Liver Function Tests (LFTs)
AST Final Visit (2 - 5.99 years)
|
0.68 ukat/L
Standard Deviation 0.185
|
|
Elevation in Liver Function Tests (LFTs)
AST Final Visit (6 - 17.99 years)
|
0.71 ukat/L
Standard Deviation 0.181
|
|
Elevation in Liver Function Tests (LFTs)
ALT Screening (Overall)
|
0.33 ukat/L
Standard Deviation 0.128
|
|
Elevation in Liver Function Tests (LFTs)
ALT Screening (6 months - 1.99 years)
|
0.34 ukat/L
Standard Deviation 0.053
|
|
Elevation in Liver Function Tests (LFTs)
ALT Screening (2 - 5.99 years)
|
0.30 ukat/L
Standard Deviation 0.129
|
|
Elevation in Liver Function Tests (LFTs)
ALT Screening (6 - 17.99 years)
|
0.35 ukat/L
Standard Deviation 0.158
|
|
Elevation in Liver Function Tests (LFTs)
ALT Final Visit (Overall)
|
0.31 ukat/L
Standard Deviation 0.110
|
|
Elevation in Liver Function Tests (LFTs)
ALT Final Visit (6 months - 1.99 years)
|
0.33 ukat/L
Standard Deviation 0.067
|
|
Elevation in Liver Function Tests (LFTs)
ALT Final Visit (2 - 5.99 years)
|
0.30 ukat/L
Standard Deviation 0.109
|
|
Elevation in Liver Function Tests (LFTs)
ALT Final Visit (6 - 17.99 years)
|
0.32 ukat/L
Standard Deviation 0.142
|
SECONDARY outcome
Timeframe: Baseline to Week 60 (or Final Visit); max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Safety and efficacy of hydroxyurea therapy
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Hemoglobin
Screening (Overall)
|
8.32 g/dL
Standard Deviation 1.114
|
|
Hemoglobin
Screening (6 months - 1.99 years)
|
9.76 g/dL
Standard Deviation 0.847
|
|
Hemoglobin
Screening (2 - 5.99 years)
|
8.07 g/dL
Standard Deviation 0.980
|
|
Hemoglobin
Screening (6 - 17.99 years)
|
7.99 g/dL
Standard Deviation 0.911
|
|
Hemoglobin
Final Visit (Overall)
|
9.47 g/dL
Standard Deviation 1.369
|
|
Hemoglobin
Final Visit (6 months - 1.99 years)
|
10.60 g/dL
Standard Deviation 1.421
|
|
Hemoglobin
Final Visit (2 - 5.99 years)
|
9.47 g/dL
Standard Deviation 1.190
|
|
Hemoglobin
Final Visit (6 - 17.99 years)
|
8.63 g/dL
Standard Deviation 1.149
|
SECONDARY outcome
Timeframe: Up to Week 60Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Bacterial Infections
Prior to Treatment (Overall)
|
7 events
|
|
Bacterial Infections
Prior to Treatment (6 months - 1.99 years)
|
0 events
|
|
Bacterial Infections
Prior to Treatment (2 - 5.99 years)
|
3 events
|
|
Bacterial Infections
Prior to Treatment (6 - 17.99 years)
|
4 events
|
|
Bacterial Infections
After Treatment (Overall)
|
17 events
|
|
Bacterial Infections
After Treatment (6 months - 1.99 years)
|
1 events
|
|
Bacterial Infections
After Treatment (2 - 5.99 years)
|
8 events
|
|
Bacterial Infections
After Treatment (6 - 17.99 years)
|
8 events
|
SECONDARY outcome
Timeframe: Up to Week 60Population: At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Viral Infections
Prior to Treatment (Overall)
|
8 Events
|
|
Viral Infections
Prior to Treatment (6 months - 1.99 years)
|
0 Events
|
|
Viral Infections
Prior to Treatment (2 - 5.99 years)
|
8 Events
|
|
Viral Infections
Prior to Treatment (6 - 17.99 years)
|
0 Events
|
|
Viral Infections
After Treatment (Overall)
|
23 Events
|
|
Viral Infections
After Treatment (6 months - 1.99 years)
|
4 Events
|
|
Viral Infections
After Treatment (2 - 5.99 years)
|
12 Events
|
|
Viral Infections
After Treatment (6 - 17.99 years)
|
7 Events
|
SECONDARY outcome
Timeframe: Up to Week 60Population: At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Fungal Infections
Prior to Treatment (Overall)
|
1 events
|
|
Fungal Infections
Prior to Treatment (6 months - 1.99 years)
|
0 events
|
|
Fungal Infections
Prior to Treatment (2 - 5.99 years)
|
0 events
|
|
Fungal Infections
Prior to Treatment (6 - 17.99 years)
|
1 events
|
|
Fungal Infections
After Treatment (Overall)
|
4 events
|
|
Fungal Infections
After Treatment (6 months - 1.99 years)
|
1 events
|
|
Fungal Infections
After Treatment (2 - 5.99 years)
|
1 events
|
|
Fungal Infections
After Treatment (6 - 17.99 years)
|
2 events
|
SECONDARY outcome
Timeframe: Up to Week 60Population: At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment.
Impact of Hydroxyurea on Safety, Hematology and Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Leg Ulcers
Prior to Treatment (Overall)
|
0 events
|
|
Leg Ulcers
Prior to Treatment (6 months -1.99 years)
|
0 events
|
|
Leg Ulcers
Prior to Treatment (2 - 5.99 years)
|
0 events
|
|
Leg Ulcers
Prior to Treatment (6 -17.99 years)
|
0 events
|
|
Leg Ulcers
After Treatment (Overall)
|
1 events
|
|
Leg Ulcers
After Treatment (6 months -1.99 years)
|
0 events
|
|
Leg Ulcers
After Treatment (2 - 5.99 years)
|
0 events
|
|
Leg Ulcers
After Treatment (6 - 17.99 years)
|
1 events
|
SECONDARY outcome
Timeframe: Baseline to Week 60 (or Final Visit); max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Biomarker endpoints of Hydroxyurea efficacy
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Fetal Hemoglobin
Screening (Overall)
|
11.90 Hemoglobin F/Total Hemoglobin %
Standard Deviation 8.711
|
|
Fetal Hemoglobin
Screening (6 months - 1.99 years)
|
21.52 Hemoglobin F/Total Hemoglobin %
Standard Deviation 6.889
|
|
Fetal Hemoglobin
Screening (2 - 5.99 years)
|
10.94 Hemoglobin F/Total Hemoglobin %
Standard Deviation 7.637
|
|
Fetal Hemoglobin
Screening (6 - 17.99 years)
|
5.57 Hemoglobin F/Total Hemoglobin %
Standard Deviation 4.641
|
|
Fetal Hemoglobin
Final Visit (Overall)
|
23.53 Hemoglobin F/Total Hemoglobin %
Standard Deviation 11.179
|
|
Fetal Hemoglobin
Final Visit (6 months - 1.99 years)
|
26.32 Hemoglobin F/Total Hemoglobin %
Standard Deviation 4.893
|
|
Fetal Hemoglobin
Final Visit (2 - 5.99 years)
|
27.09 Hemoglobin F/Total Hemoglobin %
Standard Deviation 11.888
|
|
Fetal Hemoglobin
Final Visit (6 - 17.99 years)
|
12.47 Hemoglobin F/Total Hemoglobin %
Standard Deviation 6.467
|
SECONDARY outcome
Timeframe: Baseline to Week 60 (or Final Visit); max 15 months on treatmentPopulation: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Biomarker endpoints of Hydroxyurea efficacy
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Mean Corpuscular Volume (MCV)
Screening (Overall)
|
83.13 fL
Standard Deviation 8.643
|
|
Mean Corpuscular Volume (MCV)
Screening (6 months - 1.99 years)
|
76.42 fL
Standard Deviation 7.682
|
|
Mean Corpuscular Volume (MCV)
Screening (2 - 5.99 years)
|
83.25 fL
Standard Deviation 9.715
|
|
Mean Corpuscular Volume (MCV)
Screening (6 - 17.99 years)
|
86.30 fL
Standard Deviation 5.410
|
|
Mean Corpuscular Volume (MCV)
Final Visit (Overall)
|
97.64 fL
Standard Deviation 13.700
|
|
Mean Corpuscular Volume (MCV)
Final Visit (6 months - 1.99 years)
|
81.68 fL
Standard Deviation 14.506
|
|
Mean Corpuscular Volume (MCV)
Final Visit (2 - 5.99 years)
|
102.49 fL
Standard Deviation 11.736
|
|
Mean Corpuscular Volume (MCV)
Final Visit (6 - 17.99 years)
|
100.51 fL
Standard Deviation 6.859
|
SECONDARY outcome
Timeframe: PK1 (day 1), week 20-32 (6 months) and Week 60 (Final Visit)Population: Baseline value is the last non-missing assessment prior to first exposure of oral HU. Analysis was from initiation of study drug, again at \~6months (between 20-32 weeks) and at final study visit. Week 28 (6 months - 1.99 years) no measures were analysed at this timepoint.
Biomarker Endpoints
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Cystatin C
PK1 Day 1 (Overall)
|
7.52 nmol/L
Standard Deviation 1.288
|
|
Cystatin C
PK1 Day 1 (6 months - 1.99 years)
|
8.89 nmol/L
Standard Deviation 1.170
|
|
Cystatin C
PK1 Day 1 (2 - 5.99 years)
|
6.87 nmol/L
Standard Deviation 1.001
|
|
Cystatin C
PK1 Day 1 (6 - 17.99 years)
|
7.18 nmol/L
Standard Deviation 0.549
|
|
Cystatin C
Week 24 (Overall)
|
7.50 nmol/L
Standard Deviation 1.173
|
|
Cystatin C
Week 24 (6 months - 1.99 years)
|
8.36 nmol/L
Standard Deviation 0.263
|
|
Cystatin C
Week 24 (2 - 5.99 years)
|
7.07 nmol/L
Standard Deviation 1.074
|
|
Cystatin C
Week 24 (6 - 17.99 years)
|
7.52 nmol/L
Standard Deviation 1.810
|
|
Cystatin C
Week 28 (Overall)
|
8.67 nmol/L
Standard Deviation 0.134
|
|
Cystatin C
Week 28 (2 - 5.99 years)
|
8.76 nmol/L
Standard Deviation NA
No SD possible when only n=1 participant analysed at this timepoint for this age group
|
|
Cystatin C
Week 28 (6 - 17.99 years)
|
8.57 nmol/L
Standard Deviation NA
No SD possible when only n=1 participant analysed at this timepoint for this age group
|
|
Cystatin C
Final Visit (Overall)
|
7.44 nmol/L
Standard Deviation 1.340
|
|
Cystatin C
Final Visit (6 months - 1.99 years)
|
8.63 nmol/L
Standard Deviation 0.999
|
|
Cystatin C
Final Visit (2 - 5.99 years)
|
7.19 nmol/L
Standard Deviation 1.253
|
|
Cystatin C
Final Visit (6 - 17.99 years)
|
6.80 nmol/L
Standard Deviation 1.192
|
SECONDARY outcome
Timeframe: 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMPPopulation: Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall.
Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for vaso-occlusive crisis (Mean \[SD\])
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months prior (Overall)
|
0.5 hospitalisation events per month
Standard Deviation 0.92
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months prior (6 months - 1.99 years))
|
0.0 hospitalisation events per month
Standard Deviation 0.0
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months prior (2 - 5.99 years))
|
0.7 hospitalisation events per month
Standard Deviation 1.08
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months prior (6 - 17.99 years)
|
0.6 hospitalisation events per month
Standard Deviation 0.84
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months after treatment (Overall)
|
0.2 hospitalisation events per month
Standard Deviation 0.51
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months after treatment (6 months - 1.99 years))
|
0.3 hospitalisation events per month
Standard Deviation 0.82
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months after treatment (2 - 5.99 years)
|
0.0 hospitalisation events per month
Standard Deviation 0.0
|
|
Incidence of Acute Vaso-Occlusive Pain Crises (VOC)
VOC 12months after treatment (6 - 17.99 years))
|
0.3 hospitalisation events per month
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: Up to Week 60Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. Age group (6 months to 1.99 years) did not report any blood transfusions.
Clinical status endpoints, related to blood transfusions for treatment of SCA, this may be hospitalization, A\&E, or in-clinic treatment from safety population (n=32)
Outcome measures
| Measure |
Oral Hydroxyurea
n=7 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Number and Frequency of Blood Transfusions
Overall
|
30 events (number of transfusions)
|
|
Number and Frequency of Blood Transfusions
2 years - 5.99 years
|
21 events (number of transfusions)
|
|
Number and Frequency of Blood Transfusions
6 years - 17.99 years
|
9 events (number of transfusions)
|
SECONDARY outcome
Timeframe: 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMPPopulation: Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall.
Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for Acute Chest Syndrome (Mean \[SD\])
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months prior (Overall)
|
0.5 hospitalisation events per month
Standard Deviation 0.92
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months prior (6 months - 1.99 years)
|
0.00 hospitalisation events per month
Standard Deviation 0.00
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months prior (2 - 5.99 years)
|
0.6 hospitalisation events per month
Standard Deviation 0.89
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months prior (6 - 17.99 years)
|
0.7 hospitalisation events per month
Standard Deviation 1.16
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months after treatment (Overall)
|
0.2 hospitalisation events per month
Standard Deviation 0.37
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months after treatment (6 months - 1.99 years)
|
0.00 hospitalisation events per month
Standard Deviation 0.00
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months after treatment (2 - 5.99 years)
|
0.3 hospitalisation events per month
Standard Deviation 0.45
|
|
Acute Chest Syndrome (ACS)
ACS Hospitalisations 12 months after treatment (6 - 17.99 years)
|
0.1 hospitalisation events per month
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMPPopulation: Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall.
Clinical Status endpoints, all hospitalisations (not ER/Accident without hospitalization) (Mean \[SD\])
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Hospitalizations
Hospitalisations 12 months prior (Overall)
|
1.7 hospitalisation events per month
Standard Deviation 1.54
|
|
Hospitalizations
Hospitalisations 12 months prior (6 months - 1.99 years)
|
0.3 hospitalisation events per month
Standard Deviation 0.82
|
|
Hospitalizations
Hospitalisations 12 months prior (2 - 5.99 years)
|
2.0 hospitalisation events per month
Standard Deviation 1.59
|
|
Hospitalizations
Hospitalisations 12 months prior (6 - 17.99 years)
|
1.9 hospitalisation events per month
Standard Deviation 1.45
|
|
Hospitalizations
Hospitalisations 12 months after treatment (Overall)
|
0.3 hospitalisation events per month
Standard Deviation 0.65
|
|
Hospitalizations
Hospitalisations 12 months after treatment (6 months - 1.99 years)
|
0.3 hospitalisation events per month
Standard Deviation 0.82
|
|
Hospitalizations
Hospitalisations 12 months after treatment (2 - 5.99 years)
|
0.3 hospitalisation events per month
Standard Deviation 0.45
|
|
Hospitalizations
Hospitalisations 12 months after treatment (6 - 17.99 years)
|
0.5 hospitalisation events per month
Standard Deviation 0.85
|
SECONDARY outcome
Timeframe: Screening Up to Final Visit (Week 60 or Withdrawal), maximum 15 months on IMPPopulation: Clinical status endpoints; Safety population = 32 participants, who received at least one dose of IMP. Week 60 is the final study visit, or withdrawal point at which point IMP was halted. MTD only summarized for subjects who investigator denoted as achieving MTD during the study (n=20). If several doses were marked as MTD for the subject, the highest dose was used.
Summary of maximum tolerated dose achieved in mg/kg (Mean \[SD\])
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Dose Escalation i.e. Maximum Tolerated Dose (MTD)
MTD (Overall)
|
25.63 mg/kg
Standard Deviation 6.780
|
|
Dose Escalation i.e. Maximum Tolerated Dose (MTD)
MTD (6 months - 1.99 years)
|
23.50 mg/kg
Standard Deviation 8.944
|
|
Dose Escalation i.e. Maximum Tolerated Dose (MTD)
MTD (2 - 5.99 years)
|
26.11 mg/kg
Standard Deviation 5.465
|
|
Dose Escalation i.e. Maximum Tolerated Dose (MTD)
MTD (6 - 17.99 years)
|
26.67 mg/kg
Standard Deviation 7.528
|
SECONDARY outcome
Timeframe: 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMPPopulation: Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall.
Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other Non-SCA related) (mean \[SD\])
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months prior (Overall)
|
0.4 hospitalisation events per month
Standard Deviation 0.67
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months prior (6 months - 1.99 years)
|
0.3 hospitalisation events per month
Standard Deviation 0.82
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months prior (2 - 5.99 years)
|
0.4 hospitalisation events per month
Standard Deviation 0.63
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months prior (6 - 17.99 years)
|
0.4 hospitalisation events per month
Standard Deviation 0.70
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months after treatment (Overall)
|
0.0 hospitalisation events per month
Standard Deviation 0.18
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months after treatment (6 months - 1.99 years)
|
0.00 hospitalisation events per month
Standard Deviation 0.00
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months after treatment (2 - 5.99 years)
|
0.00 hospitalisation events per month
Standard Deviation 0.00
|
|
Other SCA-related Hospitalizations
Other SCA related Hospitalizations 12 months after treatment (6 - 17.99 years)
|
0.1 hospitalisation events per month
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Taken once at any point after 8 weeks on study medication (or at early Withdrawal)Population: Results are presented for all 32 safety participants.
Clinical status endpoints. Visual Analogue scale used to determine, taste, smell, aftertaste, acceptability and ease of dosing (1-100mm scale) with 1 being worst possible and 100 being best possible. Assessed for \<6 years of age by parents/guardians. Assessed for \>6 years of age, combination of parent/guardian and participant responses.
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Taste (Overall)
|
84.2 mm
Standard Deviation 26.21
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Taste (6 months - 1.99 years)
|
71.3 mm
Standard Deviation 23.30
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Taste (2 - 5.99 years)
|
91.1 mm
Standard Deviation 23.86
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Taste (6 - 17.99 years)
|
80.8 mm
Standard Deviation 30.14
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Smell (Overall)
|
83.8 mm
Standard Deviation 21.73
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Smell (6 months - 1.99 years)
|
74.8 mm
Standard Deviation 25.51
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Smell (2 - 5.99 years)
|
87.5 mm
Standard Deviation 17.26
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Smell (6 - 17.99 years)
|
83.1 mm
Standard Deviation 26.28
|
|
Parent/Caregiver Palatability and Acceptability Questionnaire
Aftertaste (>6 years)
|
67.6 mm
Standard Deviation 23.21
|
SECONDARY outcome
Timeframe: From Screening Up to Final Visit (Week 60 or WD)Population: Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted.
Biochemistry
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Vitamin D
Screening (Overall)
|
59.35 nmol/L
Standard Deviation 32.613
|
|
Vitamin D
Screening (6 months - 1.99 years)
|
83.07 nmol/L
Standard Deviation 32.329
|
|
Vitamin D
Screening (2 - 5.99 years)
|
65.43 nmol/L
Standard Deviation 29.076
|
|
Vitamin D
Screening (6 - 17.99 years)
|
35.39 nmol/L
Standard Deviation 24.403
|
|
Vitamin D
Final Visit (Overall)
|
62.26 nmol/L
Standard Deviation 30.220
|
|
Vitamin D
Final Visit (6 months - 1.99 years)
|
86.44 nmol/L
Standard Deviation 25.475
|
|
Vitamin D
Final Visit (2 - 5.99 years)
|
57.54 nmol/L
Standard Deviation 34.093
|
|
Vitamin D
Final Visit (6 - 17.99 years)
|
52.97 nmol/L
Standard Deviation 14.749
|
SECONDARY outcome
Timeframe: 12 months prior to treatment and 12 months post-treatment; maximum 15 months on IMPPopulation: Hospitalizations 'Prior to Treatment' having a start date within 1 year prior to initial treatment. Hospitalizations 'After Treatment' defined as all hospitalizations (not ER/Accident without hospitalization) within 1 year after treatment start date.
Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other SCA-related)
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months prior (Overall)
|
0.2 events
Standard Deviation 0.47
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months prior (6 months - 1.99 years)
|
0.00 events
Standard Deviation 0.00
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months prior (2 - 5.99 years)
|
0.3 events
Standard Deviation 0.58
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months prior (6 - 17.99 years)
|
0.2 events
Standard Deviation 0.42
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months after treatment (Overall)
|
0.00 events
Standard Deviation 0.00
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months after treatment (6 months - 1.99 years)
|
0.00 events
Standard Deviation 0.00
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months after treatment (2 - 5.99 years)
|
0.00 events
Standard Deviation 0.00
|
|
Other Non-SCA-related Hospitalizations
Other Non-SCA related Hospitalizations 12 months after treatment (6 - 17.99 years)
|
0.00 events
Standard Deviation 0.00
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 40-56 (Follow up scan).Population: Time Averaged Mean Maximum Velocity (TAMV) in cm/sec at Baseline and Week 40-56 Visit (Safety Population). max 15 months on treatment at Week 60. Only participants with non-missing values at screening and end of study are included in the Baseline shift summary (change from baseline).
Exploratory Endpoint; clinical output of hydroxyurea treatment
Outcome measures
| Measure |
Oral Hydroxyurea
n=32 Participants
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Transcranial Doppler Velocity
Screening (2 - 5.99 years)
|
150.0 cm/sec
Standard Deviation 34.78
|
|
Transcranial Doppler Velocity
Screening (6 - 17.99 years)
|
148.3 cm/sec
Standard Deviation 22.42
|
|
Transcranial Doppler Velocity
Week 40-56 (Overall)
|
133.7 cm/sec
Standard Deviation 26.52
|
|
Transcranial Doppler Velocity
Week 40-56 (6 months - 1.99 years)
|
95.7 cm/sec
Standard Deviation 15.18
|
|
Transcranial Doppler Velocity
Week 40-56 (2 - 5.99 years)
|
138.6 cm/sec
Standard Deviation 24.86
|
|
Transcranial Doppler Velocity
Week 40-56 (6 - 17.99 years)
|
140.7 cm/sec
Standard Deviation 20.79
|
|
Transcranial Doppler Velocity
Baseline Shift (Overall)
|
-11.5 cm/sec
Standard Deviation 20.74
|
|
Transcranial Doppler Velocity
Baseline Shift (6 months - 1.99 years)
|
-1.0 cm/sec
Standard Deviation NA
Insufficient sample size.
|
|
Transcranial Doppler Velocity
Baseline Shift (2 - 5.99 years)
|
-13.7 cm/sec
Standard Deviation 22.02
|
|
Transcranial Doppler Velocity
Baseline Shift (6 - 17.99 years)
|
-9.0 cm/sec
Standard Deviation 20.68
|
|
Transcranial Doppler Velocity
Screening (Overall)
|
141.5 cm/sec
Standard Deviation 34.71
|
|
Transcranial Doppler Velocity
Screening (6 months - 1.99 years)
|
90.5 cm/sec
Standard Deviation 9.33
|
Adverse Events
Oral Hydroxyurea
Serious events: 6 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Oral Hydroxyurea
n=32 participants at risk
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute Chest Syndrome (ACS) Grade 3
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chest Syndrome (ACS) Grade 2
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Vaso-occlusive Crisis (VOC)
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Anemia secondary to SCD
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
Other adverse events
| Measure |
Oral Hydroxyurea
n=32 participants at risk
Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day.
Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Neutropenia/Low ANC Count
|
12.5%
4/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Thrombocytopenia/Low Platelet Count
|
15.6%
5/32 • Number of events 7 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Haemoglobin (Hb) Decreased
|
6.2%
2/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Absolute Reticulocyte Count (ARC) Decreased
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Red Blood Cell (RBC) Count Decreased
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Gamma-Glutamyltransferase (GGT) Increased
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Hematocrit (HCT) Decreased
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
4/32 • Number of events 5 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Nail Discolouration
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Rash Papular
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Sickle Cell Anemia with Crisis/Vaso-Occlusive Crisis (VOC)
|
56.2%
18/32 • Number of events 53 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.6%
5/32 • Number of events 5 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chest Syndrome (ACS)
|
6.2%
2/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Hypereosinophilic Syndrome
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Blood and lymphatic system disorders
Splenomegaly
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Ear and labyrinth disorders
Ear Pain
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Abdominal Pain
|
18.8%
6/32 • Number of events 7 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Constipation
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Gastritis
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Mouth Ulceration
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Salivary Gland Enlargement
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Teething
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Vomiting
|
18.8%
6/32 • Number of events 6 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Feeling Abnormal
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Influenza Like Illness
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Injection Site Pain
|
3.1%
1/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Injection Site Swelling
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Peripheral Swelling
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Pyrexia
|
28.1%
9/32 • Number of events 16 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Swelling Face
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
General disorders
Ulcer
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Hepatobiliary disorders
Cholecystitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Hepatobiliary disorders
Hepatomegaly
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Immune system disorders
Drug Hypersensitivity
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Body Tinea
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Chronic Sinusitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Conjunctivitis
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Conjunctivitis Viral
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
COVID-19
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Croup Infectious
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Ear Infection
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Fungal Skin Infection
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Gastroenteritis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Gingival Abscess
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Gingivitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Hand-Foot-And-Mouth Disease
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Localised Infection
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
15.6%
5/32 • Number of events 5 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
3/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Otitis Media
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Pharyngitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Pharyngotonsillitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Rhinitis
|
9.4%
3/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Sinusitis
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Tinea Capitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Tonsilitis
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
53.1%
17/32 • Number of events 43 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Urinary Tract Infection
|
6.2%
2/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Viral Infection
|
15.6%
5/32 • Number of events 7 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Viral Pharyngitis
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Infections and infestations
Viral Rash
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Arthropod Bite
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Contusion
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Forearm Fracture
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Lip Injury
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Skin Abrasion
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Soft Tissue Injury
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Injury, poisoning and procedural complications
Wound Complication
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Alanine Aminotransferase Increased
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Aspartate Aminotransferase Increased
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Blood Iron Decreased
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Body Temperature Increased
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Platelet Count Increased
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Investigations
Vitamin D Decreased
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Muscle Tightness
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Soft Tissue Swelling
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Nervous system disorders
Benign Rolandic Epilepsy
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • Number of events 8 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Nervous system disorders
Lethargy
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Psychiatric disorders
Pica
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Reproductive system and breast disorders
Balanoposthitis
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Reproductive system and breast disorders
Priapism
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Respiratory Disease
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Sinusitis
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
6.2%
2/32 • Number of events 7 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial Hyperreactivity
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
6.2%
2/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.9%
7/32 • Number of events 7 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
|
9.4%
3/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
3.1%
1/32 • Number of events 4 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.4%
3/32 • Number of events 3 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Skin Erosion
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Skin and subcutaneous tissue disorders
Urticaria Papular
|
6.2%
2/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Surgical and medical procedures
Tooth Extraction
|
3.1%
1/32 • Number of events 1 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
|
Gastrointestinal disorders
Toothache
|
3.1%
1/32 • Number of events 2 • Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged \>7days. SCA related hospitalisations \<7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
|
Additional Information
Dr Hussain Mulla, Head of Clinical Development
Nova Laboratories Ltd
Phone: 0116 223 0101
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication or sub-set analysis of data based on the results obtained shall not be made before the first publication by the Sponsor, in which the Investigators may be named as authors. After initial publication material for public dissemination will be submitted to the Sponsor for review at least 60 days prior to submission, where all reasonable comments by the Sponsor will be incorporated. Sponsor may request additional delay for up to 6 months to protect proprietary information/IP.
- Publication restrictions are in place
Restriction type: OTHER