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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT01682538
First received: September 7, 2012
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: Nitisinone, capsule
Drug: Nitisinone, suspension
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions. [ 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. ] [ Designated as safety issue: No ]
  • The Maximum Serum Concentration (Cmax) During Fasting Conditions. [ 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Area Under the Serum Concentration Curve (AUC) 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin suspension treatments arms- both fasting and with food.

  • 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin suspension treatment arms- both fasting and with food.

  • AUC From Time Zero to Infinity [ 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.

  • Time to Reach C-Max (t-Max) [ 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.

  • Terminal Half-life [ 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.

  • Oral Clearance (CL/F) [ 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.

  • Apparent Volume of Distribution (Vz/F) [ 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. ] [ Designated as safety issue: No ]
    Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.


Enrollment: 12
Study Start Date: August 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Orfadin capsules, fasting
Orfadin capsules, single dose, 30 mg
Drug: Nitisinone, capsule
Experimental: Orfadin suspension, fasting
Orfadin suspension 4 mg/mL, single dose 30 mg (7,5 mL)
Drug: Nitisinone, suspension
Experimental: Orfadin suspension, with food
Orfadin suspension 4mg/mL, single dose 30 mg (7,5 mL)
Drug: Nitisinone, suspension

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682538

Locations
Netherlands
Pharmaceutical Research Associates Group B.V (PRA)
Zuidlaren, Netherlands
Sponsors and Collaborators
Swedish Orphan Biovitrum
Investigators
Study Director: Erik Brouwer, MD Swedish Orphan Biovitrum
  More Information

No publications provided

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT01682538     History of Changes
Other Study ID Numbers: Sobi.NTBC-001
Study First Received: September 7, 2012
Results First Received: October 8, 2013
Last Updated: February 20, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Swedish Orphan Biovitrum:
Orfadin
Nitisinone
Bioequivalence
Bioavailability

Additional relevant MeSH terms:
Nitisinone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014