Bio Equivalency 20 Mgm Orfadin and 20 Mgm of Nitisonine

Study Overview
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Brief Summary
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he purpose of this study is to determine whether Nitisinone 10 mg Tablets (Test Product are bioequivalent to the reference product Orfadin 10 mg

Detailed Description
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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 4 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 nitinosine Determination of succinylacetone (SA) in blood (serum/plasma) and/or urine will be performed. Results from samples analyzed at the central laboratory, including determination of nitisinone, will be used in the evaluation of pharmacokinetics, efficacy and safety during the two treatment periods.

Official Title
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Orfadin and Nitinosine Study

Conditions
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Hereditary Tyrosinemia, Type I

Intervention / Treatment
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* Drug: Nitisinone
* Drug: Orfadin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All HT-1 patients receiving Orfadin treatment are eligible for entry. Male and female patients of all ages diagnosed with HT-1. Stable lab values, including liver values <2 ULN (ALP, ALT, AST, bilirubin, INR). Women of childbearing potential willing to use adequate contraception Signed informed consent/assent. Exclusion Criteria: Any medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion. Enrollment in another concurrent clinical interventional study within three months prior to inclusion in this study. Pregnant women. Lactating women. .Known hepatitis B, hepatitis C or HIV infection. Foreseeable inability to cooperate with given instructions or study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Orfandin .5 mgm/kg mgm bid<br>Two participant will receive .5 mgm/kg mgm of orfadin | Drug: Orfadin<br>* Orfadin<br>|
| Experimental: Nitinosine .5 mgm/kg bid<br>Two participant will receive .5 mgm/kg of nitinosine | Drug: Nitisinone<br>* Measure bio equivalency/efficacy of nitinosine and orfadin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Succinylacetone level | Succinylacetone level will be measured every 2 weeks for eight weeks | 8 weeks |