Healthy VolunteersPhase 1NCT01682538
Bioequivalence of Orfadin Suspension Compared to Orfadin Capsules, and the Effect of Food on the Bioavailability of the Suspension
A Phase 1 study testing Nitisinone, capsule and Nitisinone, suspension in people with Healthy Volunteers, run by Swedish Orphan Biovitrum at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Nitisinone, capsule and Nitisinone, suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2012to Oct 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male volunteers
- Age: 18-55 years, inclusive
- BMI: 18,5-30,0 kg/m2, inclusive
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Pharmaceutical Research Associates Group B.V (PRA)
Zuidlaren
About this study
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
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.
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- Nitisinone, capsule, Nitisinone, suspension
- Keywords
- Orfadin, Nitisinone, Bioequivalence, Bioavailability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitisinone, capsuleDrug
Nitisinone, suspensionDrug
| Study group | Role | What they receive |
|---|---|---|
| Orfadin capsules, fasting | Active comparator | Orfadin capsules, single dose, 30 mg Receives: Drug: Nitisinone, capsule |
| Orfadin suspension, fasting | Experimental | Orfadin suspension 4 mg/mL, single dose 30 mg (7,5 mL) Receives: Drug: Nitisinone, suspension |
| Orfadin suspension, with food | Experimental | Orfadin suspension 4mg/mL, single dose 30 mg (7,5 mL) Receives: Drug: Nitisinone, suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.
Measured: 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.
The Maximum Serum Concentration (Cmax) During Fasting Conditions.
Measured: 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 (7)
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.
Measured: 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.
The Maximum Serum Concentration (Cmax)
Measured for the Orfadin suspension treatment arms- both fasting and with food.
Measured: 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.
AUC From Time Zero to Infinity
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Measured: 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.
Time to Reach C-Max (t-Max)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Measured: 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.
Terminal Half-life
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Measured: 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.
Oral Clearance (CL/F)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Measured: 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.
Apparent Volume of Distribution (Vz/F)
Measured for the Orfadin capsules and suspension treatments arms - both fasting and with food.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2012 (estimated)
- Study startAug 2012
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Erik Brouwer, MD, Study director, Swedish Orphan Biovitrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01682538
- Sponsor's protocol ID
- Sobi.NTBC-001
- Status last verified
- Feb 2014
- First submitted
- 7 Sep 2012
- Last updated
- 17 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01682538
- Acronym / sponsor ID
- Sobi.NTBC-001
- Conditions
- Healthy Volunteers
- Keywords
- Orfadin, Nitisinone, Bioequivalence, Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 11 Sep 2012 (estimated)
- Results
- Posted 20 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Orfadin capsules, fasting | Active comparator | Drug: Nitisinone, capsuleOrfadin capsules, single dose, 30 mg |
| Orfadin suspension, fasting | Experimental | Drug: Nitisinone, suspensionOrfadin suspension 4 mg/mL, single dose 30 mg (7,5 mL) |
| Orfadin suspension, with food | Experimental | Drug: Nitisinone, suspensionOrfadin suspension 4mg/mL, single dose 30 mg (7,5 mL) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy male volunteers
- Age: 18-55 years, inclusive
- BMI: 18,5-30,0 kg/m2, inclusive
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitisinone, capsule | Drug | Orfadin capsules, fasting |
| Nitisinone, suspension | Drug | Orfadin suspension, fasting, Orfadin suspension, with food |
Primary outcome
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.
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.
7 secondary outcomes
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.
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Screening Protocol
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Brouwer, MD study director
Swedish Orphan Biovitrum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitisinone, capsule and Nitisinone, suspension in people with Healthy Volunteers, run by Swedish Orphan Biovitrum at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2014.