Healthy
Conditions
Keywords
Orfadin, Nitisinone, Bioequivalence
Brief summary
The purpose of this study is to evaluate the bioequivalence between Orfadin 20 mg and 10 mg capsules in healthy volunteers.
Detailed description
This is an open, randomized 2-way crossover study in 12 healthy volunteers. Subjects will receive single oral 20 mg doses of nitisinone administrated as one 20 mg capsule or as two 10 mg capsules of Orfadin. There will be a 3-week washout period between the doses. There will be a screening visit within 3 weeks prior to the first dose. During each treatment period, subjects will be admitted to the clinic from the afternoon on the day before drug administration (i.e., on Day -1) and remain at the clinic until the 48-hour post-dose blood sample has been collected in the morning of Day 3. They will then return for ambulatory visit in the morning of Day 4 (72-hour sample). A follow-up visit will take place 7-14 days after the last dose.
Interventions
DRUGNitisinone 20 mg
Nitisinone 20 mg capsules
DRUGNitisinone 10 mg
Nitisinone 10 mg capsules
Sponsors
Swedish Orphan Biovitrum
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female volunteers between 18-55 years of age, inclusive. * BMI between 18,5-30,0 kg/m2, inclusive.
Exclusion criteria
* Subjects with current keratopathy, or other abnormalities found by slit-lamp examination. * Subjects who are heavy smokers or consume more than 5 cups of coffee per day. * Subjects with history of drug and/or alcohol abuse or a positive drug screen or alcohol breath test. * Subjects with positive screens for hepatitis B surface antigen, hepatitis C antibodies and human immunodeficiency virus (HIV) 1-2 antibodies. * Subjects who were enrolled in another concurrent clinical study or intake of an investigational medicinal product within three months prior to inclusion in this study. * Subjects who donate more than 50 mL of blood within 60 days prior to drug administration or donate more than 1,5 liters of blood in the 10 months prior to first drug administration. * Female subjects that are pregnant or breastfeeding. * Female subjects of childbearing potential and all male subjects must be willing to use effective forms of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Area Under the Serum Concentration vs. Time Profile During 72 Hours After Dose (AUC72h). | 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 |
| The Maximum Serum Concentration (Cmax). | 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 |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All treatment arms | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 11 |
| Region of Enrollment Netherlands | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
The Area Under the Serum Concentration vs. Time Profile During 72 Hours After Dose (AUC72h).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nitisinone 2 x 10 mg Capsules | The Area Under the Serum Concentration vs. Time Profile During 72 Hours After Dose (AUC72h). | 262 uM*h |
| Nitisinone 1 x 20 mg Capsules | The Area Under the Serum Concentration vs. Time Profile During 72 Hours After Dose (AUC72h). | 267 uM*h |
90% CI: [0.988, 1.045]ANOVA
Primary
The Maximum Serum Concentration (Cmax).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nitisinone 2 x 10 mg Capsules | The Maximum Serum Concentration (Cmax). | 6438 nM |
| Nitisinone 1 x 20 mg Capsules | The Maximum Serum Concentration (Cmax). | 6366 nM |
90% CI: [0.945, 1.034]ANOVA