Bioequivalence of Orfadin 20 mg Compared to Orfadin 10 mg Capsules.

Study Overview
=================
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.

Official Title
-----------------
A Study to Evaluate the Bioequivalence of Orfadin Capsules 20 mg Compared to Orfadin Capsules 10 mg. An Open-label, Randomized, Cross-over, Single-dose Study in Healthy Volunteers.

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Nitisinone 20 mg
* Drug: Nitisinone 10 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitisinone 2 x 10 mg<br>Two nitisinone 10 mg capsules by mouth as a single dose | Drug: Nitisinone 10 mg<br>* Nitisinone 10 mg capsules<br>|
| Experimental: Nitisinone 1 x 20 mg capsule<br>One nitisinone 20 mg capsule by mouth as a single dose | Drug: Nitisinone 20 mg<br>* Nitisinone 20 mg capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Orfadin, Nitisinone, Bioequivalence