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

• ClinicalTrials.gov Identifier: NCT01857362
• Recruitment Status: Completed
• First Posted: May 20, 2013
• Results First Posted: October 27, 2014
• Last Update Posted: October 12, 2021
• Sponsor: Swedish Orphan Biovitrum
• Information provided by (Responsible Party): Swedish Orphan Biovitrum

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Nitisinone 20 mg; Drug: Nitisinone 10 mg	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: May 2013
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The Area Under the Serum Concentration vs. Time Profile During 72 Hours After Dose (AUC72h). [ Time Frame: 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 ]
2. The Maximum Serum Concentration (Cmax). [ Time Frame: 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Netherlands

Pharmaceutical Research Associates Group B.V (PRA)

Zuidlaren, Netherlands, 9471 GP

Sponsors and Collaborators

Swedish Orphan Biovitrum

Investigators

• Study Director: Erik Brouwer, MD; Swedish Orphan Biovitrum

More Information

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT01857362
• Other Study ID Numbers: Sobi.NTBC-004
• First Posted: May 20, 2013
• Results First Posted: October 27, 2014
• Last Update Posted: October 12, 2021
• Last Verified: September 2021

Keywords provided by Swedish Orphan Biovitrum:

Orfadin; Nitisinone; Bioequivalence

Additional relevant MeSH terms:

Nitisinone; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action