Clinical trial NCT01682538: Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Orfadin
Nitisinone
Bioequivalence
Bioavailability
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2012-09-11
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.
timeFrame: 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.
measure: The Maximum Serum Concentration (Cmax) During Fasting Conditions.
timeFrame: 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.
Secondary outcomes:
measure: The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h)
timeFrame: 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.
measure: The Maximum Serum Concentration (Cmax)
timeFrame: 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.
measure: AUC From Time Zero to Infinity
timeFrame: 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.
measure: Time to Reach C-Max (t-Max)
timeFrame: 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.
measure: Terminal Half-life
timeFrame: 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.
measure: Oral Clearance (CL/F)
timeFrame: 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.
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 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.
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: Pharmaceutical Research Associates Group B.V (PRA)
Study officials:
affiliation: Swedish Orphan Biovitrum
name: Erik Brouwer, MD
role: STUDY_DIRECTOR
References: