Trial Outcomes & Findings for Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension (NCT NCT01682538)
NCT ID: NCT01682538
Last Updated: 2014-03-17
Results Overview
COMPLETED
PHASE1
12 participants
Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.
2014-03-17
Participant Flow
First subject screened: 29 August 2012 Last subject last visit: 25 October 2012.
Participant milestones
| Measure |
All Treatment Groups
All participants received all study treatments in a randomized fashion. Subjects were allocated to one of the following treatment sequences (2 subjects to each sequence):
A B C; B C A; C A B; C B A; A C B; B A C where A=Orfadin capsules, single dose, 30 mg; B=Orfadin suspension, single dose 30 mg, fasting; C=Orfadin suspension, single dose 30 mg, fed
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension
Baseline characteristics by cohort
| Measure |
Overall Study
n=12 Participants
All treatment arms
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
35 years
STANDARD_DEVIATION 12 • n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
|
Region of Enrollment
Netherlands
|
12 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Full analysis set was used; subjects with available PK data for at least one of the treatments.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.
|
403 uM*h
Interval 315.0 to 500.0
|
346 uM*h
Interval 264.0 to 456.0
|
—
|
PRIMARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Full analysis set was used; subjects with available PK data for at least one of the treatments.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
The Maximum Serum Concentration (Cmax) During Fasting Conditions.
|
10213 nM
Interval 8030.0 to 18000.0
|
9741 nM
Interval 7780.0 to 20300.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Full analysis set was used; subjects with available PK data for at least one of the treatments.
Measured for the Orfadin suspension treatments arms- both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h)
|
346 uM*h
Interval 264.0 to 456.0
|
350 uM*h
Interval 251.0 to 467.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Full analysis set was used; subjects with available PK data for at least one of the treatments.
Measured for the Orfadin suspension treatment arms- both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
The Maximum Serum Concentration (Cmax)
|
9741 nM
Interval 7780.0 to 20300.0
|
7808 nM
Interval 5300.0 to 12500.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Per-protocol set (bioequivalence) was used for fasted treatment groups and per-protocol set (food effect) for fed treatment group (all subjects with available PK data)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
AUC From Time Zero to Infinity
|
633 h*uM
Interval 366.0 to 891.0
|
559 h*uM
Interval 454.0 to 715.0
|
577 h*uM
Interval 417.0 to 858.0
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Per protocol set (bioequivalence) was used for fasting treatments and per protocol set (food effect) used for fed treatment (all subjects with available PK data)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
Time to Reach C-Max (t-Max)
|
3.50 hours
Interval 0.75 to 8.0
|
0.38 hours
Interval 0.25 to 4.0
|
8.00 hours
Interval 3.5 to 10.0
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Per protocol set (bioequivalence) was used for fasting treatments and per protocol set (food effect) used for fed treatment (all subjects with available PK data)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
Terminal Half-life
|
48.7 hours
Interval 20.6 to 66.4
|
53.6 hours
Interval 39.3 to 63.7
|
54.3 hours
Interval 37.3 to 75.6
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Per protocol set (bioequivalence) was used for fasting treatments and per protocol set (food effect) used for fed treatment (all subjects with available PK data)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
Oral Clearance (CL/F)
|
0.145 L/h
Interval 0.102 to 0.249
|
0.160 L/h
Interval 0.127 to 0.201
|
0.158 L/h
Interval 0.106 to 0.218
|
SECONDARY outcome
Timeframe: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.Population: Per protocol set (bioequivalence) was used for fasting treatments and per protocol set (food effect) used for fed treatment (all subjects with available PK data)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Outcome measures
| Measure |
Orfadin Capsules, Fasting
n=12 Participants
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
Orfadin Suspension, With Food
n=11 Participants
Orfadin suspension 4 mg/mL, single dose, 30 mg (7,5 mL)
|
|---|---|---|---|
|
Apparent Volume of Distribution (Vz/F)
|
9.80 L
Interval 7.42 to 12.0
|
12.2 L
Interval 8.59 to 16.7
|
12.8 L
Interval 8.48 to 17.2
|
Adverse Events
Orfadin Capsules, Fasting
Orfadin Suspension, Fasting
Orfadin Suspension, With Food
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Orfadin Capsules, Fasting
n=12 participants at risk
Orfadin capsules, single dose, 30 mg
|
Orfadin Suspension, Fasting
n=12 participants at risk
Orfadin suspension 4 mg/mL, single dose, 30 mg (7.5 mL)
|
Orfadin Suspension, With Food
n=12 participants at risk
Orfadin suspension 4 mg/mL, single dose, 30 mg (7.5 mL)
|
|---|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
General disorders
Catheter site related reaction
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Infections and infestations
Nasopharyngitis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60