Trial Outcomes & Findings for Bioavailability Food-Effect Study of an Oral Nitisinone Formulation to Treat Hereditary Tyrosinemia (HT-1) (NCT NCT02750332)
NCT ID: NCT02750332
Last Updated: 2017-03-15
Results Overview
COMPLETED
PHASE1
20 participants
0 - 120 hours post-dose
2017-03-15
Participant Flow
Participant milestones
| Measure |
Treatment Sequence A (Fed) - B (Fasted)
Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fed conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period.
Nitisinone: A single oral dose of Nitisinone 10 mg Tablet will be administered.
|
Treatment Sequence B (Fasted) - A (Fed)
Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fasting conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fed conditions. Each treatment period will be separated by at least 23 calendar days of washout period.
Nitisinone: A single oral dose of Nitisinone 10 mg Tablet will be administered.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
10
|
10
|
|
Treatment Period 1
COMPLETED
|
10
|
9
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
1
|
|
Treatment Period 2
STARTED
|
10
|
9
|
|
Treatment Period 2
COMPLETED
|
10
|
9
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence A (Fed) - B (Fasted)
Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fed conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period.
Nitisinone: A single oral dose of Nitisinone 10 mg Tablet will be administered.
|
Treatment Sequence B (Fasted) - A (Fed)
Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fasting conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fed conditions. Each treatment period will be separated by at least 23 calendar days of washout period.
Nitisinone: A single oral dose of Nitisinone 10 mg Tablet will be administered.
|
|---|---|---|
|
Treatment Period 1
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Bioavailability Food-Effect Study of an Oral Nitisinone Formulation to Treat Hereditary Tyrosinemia (HT-1)
Baseline characteristics by cohort
| Measure |
All Study Participants
n=20 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black
|
18 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
South Africa
|
20 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
1168.23 ng/mL
Geometric Coefficient of Variation 22.2
|
1054.32 ng/mL
Geometric Coefficient of Variation 15.6
|
PRIMARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUC(0-120))
|
71441.92 hr*ng/mL
Geometric Coefficient of Variation 26.4
|
67242.59 hr*ng/mL
Geometric Coefficient of Variation 17.1
|
SECONDARY outcome
Timeframe: 0 - 72 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUC(0-72))
|
52976.29 hr*ng/mL
Geometric Coefficient of Variation 24.0
|
49762.02 hr*ng/mL
Geometric Coefficient of Variation 17.5
|
SECONDARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞))
|
100007.01 hr*ng/mL
Geometric Coefficient of Variation 34.5
|
90749.55 hr*ng/mL
Geometric Coefficient of Variation 19.3
|
SECONDARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax)
|
3.00 hr
Interval 2.0 to 8.0
|
6.00 hr
Interval 2.0 to 10.0
|
SECONDARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Terminal Elimination Rate Constant (λz)
|
0.011 1/hr
Geometric Coefficient of Variation 26.9
|
0.012 1/hr
Geometric Coefficient of Variation 15.7
|
SECONDARY outcome
Timeframe: 0 - 120 hours post-dosePopulation: All subjects for whom the primary PK parameters Cmax and AUC(0-120) could be calculated for at least 2 treatment periods (where one of the treatment periods is the Reference product), and who had no major protocol deviations thought to impact on the analysis of the PK data were included in the statistical PK analysis for the study.
Outcome measures
| Measure |
Test Product (Fasted)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 Participants
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2)
|
64.40 hr
Geometric Coefficient of Variation 26.9
|
59.22 hr
Geometric Coefficient of Variation 15.7
|
Adverse Events
Test Product (Fasted)
Test Product (Fed)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Test Product (Fasted)
n=20 participants at risk
A single oral dose of Nitisinone 10 mg Tablet will be administered under fasted conditions.
|
Test Product (Fed)
n=19 participants at risk
A single oral dose of Nitisinone 10 mg Tablet will be administered under fed conditions.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/20 • Adverse event data were collected over the period of the study (November 2015 - December 2015).
20 subjects were entered in to the study and randomized to either fasted or fed treatment sequence before first administration of the Investigational Medicinal Product (IMP). One subject withdrew from the study after Treatment Period 1 (Fasted) due to personal reasons. As a result, only 19 subjects completed the fed treatment.
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected over the period of the study (November 2015 - December 2015).
20 subjects were entered in to the study and randomized to either fasted or fed treatment sequence before first administration of the Investigational Medicinal Product (IMP). One subject withdrew from the study after Treatment Period 1 (Fasted) due to personal reasons. As a result, only 19 subjects completed the fed treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Itching Throat
|
0.00%
0/20 • Adverse event data were collected over the period of the study (November 2015 - December 2015).
20 subjects were entered in to the study and randomized to either fasted or fed treatment sequence before first administration of the Investigational Medicinal Product (IMP). One subject withdrew from the study after Treatment Period 1 (Fasted) due to personal reasons. As a result, only 19 subjects completed the fed treatment.
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected over the period of the study (November 2015 - December 2015).
20 subjects were entered in to the study and randomized to either fasted or fed treatment sequence before first administration of the Investigational Medicinal Product (IMP). One subject withdrew from the study after Treatment Period 1 (Fasted) due to personal reasons. As a result, only 19 subjects completed the fed treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place