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

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.

The purpose of this study is to evaluate the bioequivalence between Orfadin 20 mg and 10 mg capsules in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Nitisinone 10 mg; Drug: Nitisinone 20 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9471 GP
    • Pharmaceutical Research Associates Group B.V (PRA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Nitisinone 2 x 10 mg; Two nitisinone 10 mg capsules by mouth as a single dose	Drug: Nitisinone 10 mg; Nitisinone 10 mg capsules
EXPERIMENTAL: Nitisinone 1 x 20 mg capsule; One nitisinone 20 mg capsule by mouth as a single dose	Drug: Nitisinone 20 mg; Nitisinone 20 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (ESTIMATE): May 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Bioequivalence; Nitisinone; Orfadin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nitisinone
• Other Study ID Numbers: Sobi.NTBC-004