Trial Outcomes & Findings for Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects (NCT NCT06481709)
NCT ID: NCT06481709
Last Updated: 2025-06-12
Results Overview
Area under the concentration-time curve from time zero until the last observed concentration, as calculated by the linear up/log down variant of the trapezoidal method
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.
Results posted on
2025-06-12
Participant Flow
Participant milestones
| Measure |
Sequence DCAB
The Subject receives in this order
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence ADBC
The Subject receives in this order
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence BACD
The Subject receives in this order
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence CBDA
The Subject receives in this order
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
2
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
2
|
0
|
Reasons for withdrawal
| Measure |
Sequence DCAB
The Subject receives in this order
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence ADBC
The Subject receives in this order
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence BACD
The Subject receives in this order
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
Sequence CBDA
The Subject receives in this order
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
Baseline Characteristics
Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects
Baseline characteristics by cohort
| Measure |
All Patients Included in the 4 Sequences (DCAB;ADBC;BACD;CBDA)
n=16 Participants
Where the Subject receives these treatments according to the order of the assigned sequence
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
RLF-OD032: 100 mg/mL oral suspension
Kuvan: 100 mg powder for oral solution
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
31 years
STANDARD_DEVIATION 10 • n=99 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
Canada
|
16 participants
n=99 Participants
|
|
weight
|
70.4 kg
STANDARD_DEVIATION 10.3 • n=99 Participants
|
|
BMI
|
25 kg/m^2
STANDARD_DEVIATION 4 • n=99 Participants
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D
Area under the concentration-time curve from time zero until the last observed concentration, as calculated by the linear up/log down variant of the trapezoidal method
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=16 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=14 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Uncorrected Sapropterin AUC0-t
|
989.77 hr*ng/mL
Standard Deviation 548.82
|
837.20 hr*ng/mL
Standard Deviation 258.17
|
835.52 hr*ng/mL
Standard Deviation 276.42
|
791.64 hr*ng/mL
Standard Deviation 180.57
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D
Area under the concentration-time curve from time zero until the last observed concentration, as calculated by the linear up/log down variant of the trapezoidal method
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=16 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=14 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Baseline-corrected Sapropterin AUC0-t
|
933.65 hr*ng/mL
Standard Error 539.81
|
783.15 hr*ng/mL
Standard Error 251.59
|
780.09 hr*ng/mL
Standard Error 255.94
|
737.30 hr*ng/mL
Standard Error 166.92
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D
Maximum observed concentration
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=16 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=14 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Uncorrected Sapropterin Cmax
|
170.45 ng/mL
Standard Deviation 119.43
|
127.64 ng/mL
Standard Deviation 63.98
|
121.92 ng/mL
Standard Deviation 60.07
|
127.99 ng/mL
Standard Deviation 37.39
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D
Maximum observed concentration
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=16 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=14 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Baseline-corrected Sapropterin Cmax
|
168.30 ng/mL
Standard Deviation 119.22
|
125.55 ng/mL
Standard Deviation 63.74
|
119.81 ng/mL
Standard Deviation 59.30
|
125.87 ng/mL
Standard Deviation 36.82
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D; 1 Subject under treatment B and C not considered due to a concentration-time profiles with the terminal linear phase not clearly defined
Area under the concentration-time curve from time zero to infinity (extrapolated)
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=15 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=13 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Uncorrected Sapropterin AUC0-inf
|
1018.13 hr*ng/mL
Standard Deviation 544.08
|
885.12 hr*ng/mL
Standard Deviation 257.50
|
848.05 hr*ng/mL
Standard Deviation 288.09
|
818.89 hr*ng/mL
Standard Deviation 185.13
|
PRIMARY outcome
Timeframe: Time points 1, 0.5, pre-dose (0-hour), and 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, and 24 hours post-dose.Population: 2 Subjects didn't complete the treatment phase with C and D; 1 Subject under treatment B and C not considered due to a concentration-time profiles with the terminal linear phase not clearly defined
Area under the concentration-time curve from time zero to infinity (extrapolated)
Outcome measures
| Measure |
Treatment A
n=16 Participants
Where
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
|
Treatment B
n=15 Participants
Where
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
|
Treatment C
n=13 Participants
Where
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
|
Treatment D
n=14 Participants
Where
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
|
|---|---|---|---|---|
|
Baseline-corrected Sapropterin AUC0-inf
|
943.10 hr*ng/mL
Standard Deviation 537.40
|
813.04 hr*ng/mL
Standard Deviation 254.02
|
783.20 hr*ng/mL
Standard Deviation 263.36
|
747.35 hr*ng/mL
Standard Deviation 167.02
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment C
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Treatment D
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=16 participants at risk
The Subject receives, according to the assigned sequence, this treatment:
A is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fasting conditions.
\*RLF-OD032: 100 mg/mL oral suspension
|
Treatment B
n=16 participants at risk
The Subject receives, according to the assigned sequence, this treatment:
B is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered without water under fed conditions.
\*RLF-OD032: 100 mg/mL oral suspension
|
Treatment C
n=14 participants at risk
The Subject receives, according to the assigned sequence, this treatment:
C is 1 x 10 mg/kg dose\* of sapropterin dihydrochloride oral suspension 100 mg/mL administered with water under fed conditions.
\*RLF-OD032: 100 mg/mL oral suspension
|
Treatment D
n=14 participants at risk
The Subject receives, according to the assigned sequence, this treatment:
D is 1 x 10 mg/kg dose\* of Kuvan (sapropterin dihydrochloride) 100 mg powder for oral solution dissolved in water and administered under fed conditions
\*Kuvan: 100 mg powder for oral solution
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
7.1%
1/14 • Number of events 1 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
|
Nervous system disorders
Headache
|
6.2%
1/16 • Number of events 1 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
7.1%
1/14 • Number of events 1 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/16 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
6.2%
1/16 • Number of events 1 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
0.00%
0/14 • Approximately 30 days (From ICF signature to the last scheduled study procedure)
|
Additional Information
Giorgio Reiner Chief Scientific Officer
APR Applied Pharma Research s.a.
Phone: +41.91.6957020
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place