Trial Outcomes & Findings for A Phase 2 Study of the Effects of 6R-BH4 in Subjects With Sickle Cell Disease (NCT NCT00445978)
NCT ID: NCT00445978
Last Updated: 2021-02-25
Results Overview
A treatment-emergent adverse events (TEAE) is any adverse events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
Up to 16 weeks
Results posted on
2021-02-25
Participant Flow
This was a multicenter dose escalation study with 12 sites in the US in subjects with sickle cell disease (SCD). Only subjects with HbSS (homozygous SCD) and HbSC (heterozygous SCD) genotypes and at least 15 years of age were enrolled.
Dose escalation was to take place at Week 4, 8, and 12; however some subjects initially maintained the previous dose and received escalated doses at a later time point during the dose interval. This delay was to adhere to the study protocol for escalation (for example, if a subject missed the appointment for PAT testing, dose escalation was delayed until testing could be performed), not due to safety concerns. Subjects not escalated in dose either maintained or reduced dose.
Participant milestones
| Measure |
Sapropterin Dihydrochloride
Sapropterin dihydrochloride: Subjects will receive oral tablets, once-daily (for 2.5, 5, 10mg/kg/day doses) or twice-daily (for the 20 mg/kg/day dose) of sapropterin dihydrochloride during a 16-week dose escalation phase, with dose levels increasing within subjects every 4 weeks as follows: 2.5, 5, 10, and 20 mg/kg/day. Prior to dose escalation, the investigator evaluated each subject's safety profile at the previous dose level to determine if the subject would escalate to the next dose level; maintain the same dose; or de-escalate to the previous dose.
|
|---|---|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
STARTED
|
32
|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
COMPLETED
|
29
|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
NOT COMPLETED
|
3
|
|
Week 4 - Week 8 (5 mg/kg/Day)
STARTED
|
29
|
|
Week 4 - Week 8 (5 mg/kg/Day)
Received Escalated Dose
|
29
|
|
Week 4 - Week 8 (5 mg/kg/Day)
COMPLETED
|
25
|
|
Week 4 - Week 8 (5 mg/kg/Day)
NOT COMPLETED
|
4
|
|
Week 8 - Week 12 (10 mg/kg/Day)
STARTED
|
25
|
|
Week 8 - Week 12 (10 mg/kg/Day)
Received Escalated Dose
|
25
|
|
Week 8 - Week 12 (10 mg/kg/Day)
COMPLETED
|
24
|
|
Week 8 - Week 12 (10 mg/kg/Day)
NOT COMPLETED
|
1
|
|
Week 12 - Week 16 (20 mg/kg/Day)
STARTED
|
24
|
|
Week 12 - Week 16 (20 mg/kg/Day)
Received Escalated Dose
|
21
|
|
Week 12 - Week 16 (20 mg/kg/Day)
COMPLETED
|
23
|
|
Week 12 - Week 16 (20 mg/kg/Day)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Sapropterin Dihydrochloride
Sapropterin dihydrochloride: Subjects will receive oral tablets, once-daily (for 2.5, 5, 10mg/kg/day doses) or twice-daily (for the 20 mg/kg/day dose) of sapropterin dihydrochloride during a 16-week dose escalation phase, with dose levels increasing within subjects every 4 weeks as follows: 2.5, 5, 10, and 20 mg/kg/day. Prior to dose escalation, the investigator evaluated each subject's safety profile at the previous dose level to determine if the subject would escalate to the next dose level; maintain the same dose; or de-escalate to the previous dose.
|
|---|---|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
Adverse Event
|
1
|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
Physician Decision
|
1
|
|
Week 0 - Week 4 (2.5 mg/kg/Day)
Study Compliance
|
1
|
|
Week 4 - Week 8 (5 mg/kg/Day)
Adverse Event
|
1
|
|
Week 4 - Week 8 (5 mg/kg/Day)
Physician Decision
|
1
|
|
Week 4 - Week 8 (5 mg/kg/Day)
Lost to Follow-up
|
1
|
|
Week 4 - Week 8 (5 mg/kg/Day)
Withdrew Consent
|
1
|
|
Week 8 - Week 12 (10 mg/kg/Day)
Pregnancy
|
1
|
|
Week 12 - Week 16 (20 mg/kg/Day)
Lost to Follow-up
|
1
|
Baseline Characteristics
A Phase 2 Study of the Effects of 6R-BH4 in Subjects With Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
Sapropterin Dihydrochloride
n=32 Participants
Sapropterin dihydrochloride: Subjects will receive oral tablets, once-daily (for 2.5, 5, 10mg/kg/day doses) or twice-daily (for the 20 mg/kg/day dose) of sapropterin dihydrochloride during a 16-week dose escalation phase, with dose levels increasing within subjects every 4 weeks as follows: 2.5, 5, 10, and 20 mg/kg/day.
|
|---|---|
|
Age, Continuous
|
28.5 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
32 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
|
SCD Genotype
SS (homozygous, 2 hemoglobin S alleles)
|
19 participants
n=5 Participants
|
|
SCD Genotype
SC (heterozygous, 1 hemoglobin S allele, 1 hemoglobin C allele)
|
13 participants
n=5 Participants
|
|
PAT (peripheral arterial tonometry) at baseline (Ratio)
Normal (PAT > 1.67)
|
9 Participants
n=5 Participants
|
|
PAT (peripheral arterial tonometry) at baseline (Ratio)
Abnormal (PAT</= 1.67)
|
18 Participants
n=5 Participants
|
|
PAT (peripheral arterial tonometry) at baseline (Ratio)
Missing
|
5 Participants
n=5 Participants
|
|
TRV (tricuspid regurgitant velocity) at baseline (m/sec)
TRV< 2.5
|
18 Participants
n=5 Participants
|
|
TRV (tricuspid regurgitant velocity) at baseline (m/sec)
TRV>/= 2.5
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 16 weeksPopulation: All Treated Subjects
A treatment-emergent adverse events (TEAE) is any adverse events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Outcome measures
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=32 Participants
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
n=29 Participants
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
n=25 Participants
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
n=21 Participants
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Subjects with any adverse event
|
27 Participants
|
18 Participants
|
20 Participants
|
15 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Subjects with any serious adverse events
|
3 Participants
|
2 Participants
|
6 Participants
|
3 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Subjects with any treatment-related adverse event
|
9 Participants
|
4 Participants
|
6 Participants
|
3 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Any subject with a treatment-related serious adverse event
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Any subject with an AE causing study discontinuation
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Any subject with an SAE causing study discontinuation
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Baseline, Week 4, 8, 12 and 16.Population: At each timepoint of the dose-escalation phase, subjects with evaluable PAT score at the corresponding timepoint and baseline were included in the change from baseline analysis.
The PAT score was calculated using the ratio between the arterial pulse wave amplitude following a 5-minute arterial occlusion in the forearm to the pre-occlusion value (Reactive Hyperemia Index). A value of \</= 1.67 represents an impaired response or endothelial dysfunction. Change in PAT from Baseline to posttreatment visit is calculated by subtracting the Baseline measurement from the posttreatment measurement.
Outcome measures
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=27 Participants
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores
Baseline
|
1.5815 Ratio
Standard Deviation 0.4292
|
—
|
—
|
—
|
|
Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores
Change from Baseline to Week 4
|
0.1317 Ratio
Standard Deviation 0.4811
|
—
|
—
|
—
|
|
Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores
Change from Baseline to Week 8
|
0.2852 Ratio
Standard Deviation 0.6020
|
—
|
—
|
—
|
|
Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores
Change from Baseline to Week 12
|
0.3656 Ratio
Standard Deviation 0.5004
|
—
|
—
|
—
|
|
Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores
Change from Baseline to Week 16
|
0.3604 Ratio
Standard Deviation 0.8800
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Baseline, Week 4, 8, 12 and 16.Population: At each timepoint of the dose-escalation phase, subjects with urine 8-isoprostane at the corresponding timepoint and baseline were included in the change from baseline analysis.
Change in urine 8-isoprostane from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement. This outcome was used to assess change in oxidative stress.
Outcome measures
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=32 Participants
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Change From Baseline in the Urine 8-Isoprostane
Baseline
|
1019.68 pg/mg creatinine
Standard Deviation 479.90
|
—
|
—
|
—
|
|
Change From Baseline in the Urine 8-Isoprostane
Change from Baseline to Week 4
|
-27.58 pg/mg creatinine
Standard Deviation 622.53
|
—
|
—
|
—
|
|
Change From Baseline in the Urine 8-Isoprostane
Change from Baseline to Week 8
|
-69.75 pg/mg creatinine
Standard Deviation 402.83
|
—
|
—
|
—
|
|
Change From Baseline in the Urine 8-Isoprostane
Change from Baseline to Week 12
|
24.71 pg/mg creatinine
Standard Deviation 355.71
|
—
|
—
|
—
|
|
Change From Baseline in the Urine 8-Isoprostane
Change from Baseline to Week 16
|
-275.19 pg/mg creatinine
Standard Deviation 566.99
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Baseline, Week 4, 8, 12 and 16.Population: At each timepoint of the dose-escalation phase, subjects with urinary spot albumin to creatinine at the corresponding timepoint and baseline were included in the change from baseline analysis.
Change in Urine Albumin to Creatinine Ratio from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement. This outcome was used to assess change in renal function.
Outcome measures
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=26 Participants
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Change From Baseline in the Urine Spot Albumin to Creatinine Ratio
Baseline
|
17.88 mg/mmol
Standard Deviation 42.44
|
—
|
—
|
—
|
|
Change From Baseline in the Urine Spot Albumin to Creatinine Ratio
Change from Baseline to Week 4
|
1.66 mg/mmol
Standard Deviation 27.43
|
—
|
—
|
—
|
|
Change From Baseline in the Urine Spot Albumin to Creatinine Ratio
Change from Baseline to Week 8
|
-5.51 mg/mmol
Standard Deviation 25.31
|
—
|
—
|
—
|
|
Change From Baseline in the Urine Spot Albumin to Creatinine Ratio
Change from Baseline to Week 12
|
-10.76 mg/mmol
Standard Deviation 24.73
|
—
|
—
|
—
|
|
Change From Baseline in the Urine Spot Albumin to Creatinine Ratio
Change from Baseline to Week 16
|
-9.32 mg/mmol
Standard Deviation 23.82
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Baseline, Week 4, 8, 12 and 16.Population: At each timepoint of the dose-escalation phase, subjects with tricuspid regurgitant velocity at the corresponding timepoint and baseline were included in the change from baseline analysis.
Change in tricuspid regurgitant velocity (TRV) from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement.
Outcome measures
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=32 Participants
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Change From Baseline in the Tricuspid Regurgitant Velocity (TRV)
Change from Baseline to Week 12
|
0.01 m/sec
Standard Deviation 0.43
|
—
|
—
|
—
|
|
Change From Baseline in the Tricuspid Regurgitant Velocity (TRV)
Change from Baseline to Week 16
|
0.16 m/sec
Standard Deviation 0.72
|
—
|
—
|
—
|
|
Change From Baseline in the Tricuspid Regurgitant Velocity (TRV)
Baseline
|
2.09 m/sec
Standard Deviation 0.84
|
—
|
—
|
—
|
|
Change From Baseline in the Tricuspid Regurgitant Velocity (TRV)
Change from Baseline to Week 4
|
0.09 m/sec
Standard Deviation 0.53
|
—
|
—
|
—
|
|
Change From Baseline in the Tricuspid Regurgitant Velocity (TRV)
Change from Baseline to Week 8
|
0.03 m/sec
Standard Deviation 0.73
|
—
|
—
|
—
|
Adverse Events
Sapropterin Dihydrochloride 2.5 mg/kg/Day
Serious events: 3 serious events
Other events: 27 other events
Deaths: 0 deaths
Sapropterin Dihydrochloride 5.0 mg/kg/Day
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Sapropterin Dihydrochloride 10.0 mg/kg/Day
Serious events: 6 serious events
Other events: 20 other events
Deaths: 0 deaths
Sapropterin Dihydrochloride 20.0 mg/kg/Day
Serious events: 3 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=32 participants at risk
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
n=29 participants at risk
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
n=25 participants at risk
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
n=21 participants at risk
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
|
9.4%
3/32 • Up to 16 weeks
|
6.9%
2/29 • Up to 16 weeks
|
20.0%
5/25 • Up to 16 weeks
|
14.3%
3/21 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Nervous system disorders
Migraine
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
Other adverse events
| Measure |
Sapropterin Dihydrochloride 2.5 mg/kg/Day
n=32 participants at risk
Sapropterin dihydrochloride 2.5 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 5.0 mg/kg/Day
n=29 participants at risk
Sapropterin dihydrochloride 5.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 10.0 mg/kg/Day
n=25 participants at risk
Sapropterin dihydrochloride 10.0 mg/kg/day at Incidence
|
Sapropterin Dihydrochloride 20.0 mg/kg/Day
n=21 participants at risk
Sapropterin dihydrochloride 20.0 mg/kg/day at Incidence
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
|
28.1%
9/32 • Up to 16 weeks
|
24.1%
7/29 • Up to 16 weeks
|
40.0%
10/25 • Up to 16 weeks
|
19.0%
4/21 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
General disorders
Pyrexia
|
6.2%
2/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
General disorders
Non-cardiac chest pain
|
6.2%
2/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Asthenia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Nausea
|
6.2%
2/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
2/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Infections and infestations
Urinary tract infection
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Infections and infestations
Nasopharyngitis
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
3.1%
1/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
3.1%
1/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.4%
3/32 • Up to 16 weeks
|
10.3%
3/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
9.5%
2/21 • Up to 16 weeks
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Nervous system disorders
Insomnia
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
8.0%
2/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Nervous system disorders
Migraine
|
6.2%
2/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Electrocardiogram T wave abnormal
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Cyst
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
General disorders
Fatigue
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Flank pain
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Oedma
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Pain
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Immune system disorders
Allergic Sinusitis
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Injury, poisoning and procedural complications
Injury
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Eye disorders
Ocular icterus
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Endocrine disorders
Goitre
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Reproductive system and breast disorders
Vaginal Pain
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Reproductive system and breast disorders
Menstrual disorder
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
General disorders
Tenderness
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Abdominal pain lower
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Dental caries
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Gastroenteritis viral
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Gastrointestinal disorders
Stomach discomfort
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Bronchitis acute
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Hordeolum
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Infection
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Otitis media
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Otitis media acute
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Infections and infestations
Sinusitis
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Skin papilloma
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal oedema
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Gout
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint sprain
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Sacral pain
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Alanine aminotransferase increased
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Albumin urine
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Albumin urine present
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Blood bicarbonate decreased
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Blood creatinine increased
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Blood pressure increased
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Blood uric acid increased
|
3.1%
1/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Cardiac mumur
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Liver function test abnormal
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Mammogram abnormal
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Urinary sediment present
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
Weight increased
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Investigations
White blood cells urine positive
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypervolaemia
|
0.00%
0/32 • Up to 16 weeks
|
3.4%
1/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Metabolism and nutrition disorders
Vitamin B12 deficiency
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Vascular disorders
Arterial thrombosis limb
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Vascular disorders
Ecchymosis
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Vascular disorders
Orthostatic hypotension
|
3.1%
1/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Cardiac disorders
Bundle branch block right
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
4.0%
1/25 • Up to 16 weeks
|
0.00%
0/21 • Up to 16 weeks
|
|
Infections and infestations
Urinary tract infection fungal
|
0.00%
0/32 • Up to 16 weeks
|
0.00%
0/29 • Up to 16 weeks
|
0.00%
0/25 • Up to 16 weeks
|
4.8%
1/21 • Up to 16 weeks
|
Additional Information
Joshua Lilienstein/Medical Director, Global Medical Affairs
BioMarin Pharmaceutical Inc.
Phone: 651.523.0310
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60