Clinical Trial: Bioequivalence Study of Two Oral Nitisinone Formulations to Treat Hereditary Tyrosinemia (HT-1)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Three-Period Crossover Study to Determine the Bioequivalence of Two Oral Formulations Containing Nitisinone 10 mg Compared to Reference Formulation Orfadin In Healthy Subjects Under Fasting Conditio

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 Summary:

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).


Sponsor: Cycle Pharmaceuticals Ltd.

Current Primary Outcome:

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 - 120 hours post-dose ]
  • Area Under the Plasma Concentration Versus Time Curve (AUC(0-120)) [ Time Frame: 0 - 120 hours post-dose ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Area Under the Plasma Concentration Versus Time Curve (AUC(0-72)) [ Time Frame: 0 - 72 hours post-dose ]
  • Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞)) [ Time Frame: 0 - 120 hours post-dose ]
  • Time to Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 - 120 hours post-dose ]
  • Terminal Elimination Rate Constant (λz) [ Time Frame: 0 - 120 hours post-dose ]
  • Apparent Terminal Elimination Half-life (t1/2) [ Time Frame: 0 - 120 hours post-dose ]


Original Secondary Outcome: Same as current

Information By: Cycle Pharmaceuticals Ltd.

Dates:
Date Received: April 21, 2016
Date Started: March 2016
Date Completion:
Last Updated: October 19, 2016
Last Verified: October 2016