Conditions: Hereditary Tyrosinemia, Type I
Keywords: HT-1 Tyrosinemia Nitisinone Bioavailability Healthy Volunteer Food-Effect
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 24
Healthy volunteers: yes

Brief summary:
The purpose of this study is to determine whether Nitisinone 10 mg Tablets (Test Product 1) and Nitisinone 10 mg Tablets 'Baked' for 6 months @ 40°C/75% RH (Test Product 2) are bioequivalent to the reference product Orfadin 10 mg hard capsules.

Detailed description:
The specific aim is to conduct a randomized, single dose, three-period crossover bioequivalence study in at least 18 healthy male and female subjects at a single study center to evaluate the in vivo performance of two formulations of Nitisinone 10 mg and the reference product Orfadin under fasting.

A total of 24 healthy female and male volunteers (age 18 to 55 years old) will be entered into the study. Volunteers will be determined to be free of significant medical conditions as assessed by medical history, physical examination, and blood and urine tests. Volunteers will be randomly allocated to a treatment sequence, before administration of investigational medicinal product (IMP) under fasting conditions.

There will be a minimum 23 calendar days washout between treatments. Blood samples will be collected at pre-dose (0 hours) and at 15 minutes, 30 minutes, 1 hour, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 96 hours and 120 hours post-dose (total: 21 samples per treatment period).

Arms:
arm 1: Subjects will receive a single 10 mg tablet of Nitisinone (Test Product 1 (TP 1)) in treatment period 1, 10 mg tablet of Nitisinone Baked Tablet (Test Product 2 (TP 2)) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. arm 2: Subjects will receive a single 10 mg tablet of Nitisinone (Test Product 1) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone Baked Tablet (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. arm 3: Subjects will receive a single 10 mg tablet of Nitisinone Baked Tablet (Test Product 2) in treatment period 1, 10 mg tablet of Nitisinone (Test Product 1) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. arm 4: Subjects will receive a single 10 mg tablet of Nitisinone Baked Tablet (Test Product 2) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone (Test Product 1) in treatment period 3, and under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. arm 5: Subjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone (Test Product 1) in treatment period 2, and 10 mg tablet of Nitisinone Baked Tablet (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. arm 6: Subjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone Baked Tablet (Test Product 2) in treatment period 2, and 10 mg tablet of Nitisinone (Test Product 1) in treatment period 3, and under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period.

Interventions: intervention 1: Nitisinone intervention 2: Nitisinone Baked Tablet intervention 3: Orfadin
Intervention descriptions: intervention 1: A single oral dose of Nitisinone 10 mg Tablet will be administered. intervention 2: A single oral dose of Nitisinone 10 mg Tablet (6 months @ 40°C/75% RH) will be administered. intervention 3: A single oral dose of Orfadin 10 mg hard capsule will be administered.

Protocol document: