Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension

Healthy Volunteers Clinical Trial

Official title:

A Study to Evaluate the Bioequivalence of Orfadin Suspension 4 mg/mL Compared to Orfadin Capsules 10 mg, and the Effect of Food on the Bioavailability of the Suspension. An Open-label, Randomized, Cross-over, Single-dose Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01682538
• Other study ID #: Sobi.NTBC-001
• Status: Completed
• Phase: Phase 1
• First received: September 7, 2012
• Last updated: February 20, 2014
• Start date: August 2012
• Est. completion date: October 2012

Study information

• Verified date: February 2014
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The study is primarily being performed in order to demonstrate bioequivalence between the Orfadin (nitisinone) suspension and the marketed capsule formulation. The study will also contain a comparison of the bioavailability of the suspension given with food and on an empty stomach.

Description:

This is an open, randomized 3-way crossover study in 12 healthy volunteers. Subjects will receive single oral 30-mg doses of nitisinone as a suspension (fasting and with food) and as hard gelatin capsules (fasting only). There will be a 2-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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male volunteers

• Age: 18-55 years, inclusive

• BMI: 18,5-30,0 kg/m2, inclusive

Exclusion Criteria:

• heavy smokers

• Consumption of more than 4 cups of coffee per day.

• History of drug and/or alcohol abuse.

• Positive drug screen or alcohol breath test.

• Positive screens for hepatitis B surface antigen, hepatitis C antibodies and human immunodeficiency virus (HIV) 1-2 antibodies.

• Enrollment in another concurrent clinical study

• Intake of an investigational medicinal product within three months prior to inclusion in this study.

• Donation of more than 50 mL of blood within 60 days prior to drug administration

• Donation of more than 1,5 liters of blood in the 10 months prior to first drug administration.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Nitisinone, capsule

• Nitisinone, suspension

Locations

Country	Name	City	State
Netherlands	Pharmaceutical Research Associates Group B.V (PRA)	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.		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.	No
Primary	The Maximum Serum Concentration (Cmax) During Fasting Conditions.		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.	No
Secondary	The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h)	Measured for the Orfadin suspension treatments arms- both fasting and with food.	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.	No
Secondary	The Maximum Serum Concentration (Cmax)	Measured for the Orfadin suspension treatment arms- both fasting and with food.	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.	No
Secondary	AUC From Time Zero to Infinity	Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.	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.	No
Secondary	Time to Reach C-Max (t-Max)	Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.	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.	No
Secondary	Terminal Half-life	Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.	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.	No
Secondary	Oral Clearance (CL/F)	Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.	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.	No
Secondary	Apparent Volume of Distribution (Vz/F)	Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.	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.	No