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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 October 23, 2014