Hereditary Tyrosinemia, Type IPhase 1NCT02750332
Bioavailability Food-Effect Study of an Oral Nitisinone Formulation to Treat Hereditary Tyrosinemia (HT-1)
A Phase 1 study testing Nitisinone in people with Hereditary Tyrosinemia, Type I, run by Cycle Pharmaceuticals Ltd. at 1 site in South Africa.
Trial summary
The purpose of this study is to compare the bioavailability of the Test Product, Nitisinone 10 mg Tablet, under fasting and fed conditions (food-effect). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Tyrosinemia, Type I
- What is being tested?
- Nitisinone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Africa
- Study dates
- Nov 2015to Jan 2016
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female subjects, 18 to 55 years (both inclusive) at signing of informed consent.
- Body Mass Index (BMI) between 18.5 and 30 kg/m2 (inclusive).
- Body mass not less than 50 kg.
- Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study.
- Non-smokers.
- Females, if:
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- Of childbearing potential, the following conditions are to be met:
- Negative pregnancy test If this test is positive, the subject will be excluded from the study. In the rare circumstance that a pregnancy is discovered after the subject received IMP, every attempt must be made to follow her to term.
- Not lactating
- Abstaining from sexual activity (if this is the usual lifestyle of the subject) or must agree to use an accepted method of contraception, and agree to continue with the same method throughout the study Examples of reliable methods of contraception include non-hormonal intrauterine device, and barrier methods combined with an additional contraceptive method. In this study the concomitant use of hormonal contraceptives is NOT allowed. Other methods, if considered by the investigator as reliable, will be accepted.
- Written consent given for participation in the study.
- Subjects must be willing to consume the meal prescribed with administration of the IMP in full and within the required time.
Who cannot join
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
- Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females.
- Consumption of more than 5 cups of coffee (or equivalent amounts of caffeine) per day.
- Regular exposure to substances of abuse (other than alcohol) within the past year.
- Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks before the first administration of investigational medicinal product (IMP) except if this will not affect the outcome of the study in the opinion of the investigator.
- In this study the concomitant use of hormonal contraceptives is NOT allowed.
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- Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 10 elimination half-lives for chemical entities or 2 elimination half-lives for antibodies or insulin), whichever is the longer) before administration of IMP in this study, at the discretion of the investigator.
- Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
- A major illness during the 3 months before commencement of the screening period.
- History of hypersensitivity or allergy to the IMP or its excipients or any related medication.
- History of bronchial asthma or any other bronchospastic disease.
- History of convulsions.
- History of porphyria.
- Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.
- Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP.
- Diagnosis of hypotension made during the screening period.
- Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
- Resting pulse of > 100 beats per minute or < 40 beats per minute during the screening period, either supine or standing.
- Positive testing for human immunodeficiency virus (HIV), Hepatitis B and Hepatitis C.
- Positive urine screen for drugs of abuse. In case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the investigator.
- Positive urine screen for tobacco use.
- Positive pregnancy test.
- Female subjects that are pregnant or breastfeeding.
- Difficulty in swallowing.
- Any specific investigational product safety concern.
- Vulnerable subjects, e.g. persons in detention.
- Subjects with current keratopathy, or other clinically significant abnormalities found by slit-lamp examination (cataracts) at the discretion of the investigator.
- Concomitant use of medications that are metabolized by CYP2C9 (ibuprofen, diclofenac and indomethacin).
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Bloemfontein Early Phase Clinical Unit, PAREXEL International (South Africa)
Bloemfontein, Free State, 9301
About this study
Official title: A Single Center, Single-Dose, Open-Label, Randomized Study to Compare the Bioavailability of an Oral Test Formulation Containing Nitisinone 10 mg in at Least 16 Healthy Male and Female Subjects Under Fasting and Fed Conditions
The purpose of this study is to compare the bioavailability of the Test Product, Nitisinone 10 mg Tablet, under fasting and fed conditions (food-effect).
Read the detailed description
The specific aim is to conduct a randomized, single dose, two-period crossover bioavailability study in at least 16 healthy male and female subjects at a single study center to evaluate the in vivo performance of Test Product, Nitisinone 10 mg Tablet, under fasting and fed conditions.
The study in healthy male and female volunteers is designed to establish a pharmacokinetic (PK) profile under fed and fasting conditions for the orally administered Test Product, Nitisinone 10 mg Tablets.
A total of 20 healthy female and male volunteers (age 18 to 55 years old) will be entered into the study. Volunteers will be determined to be free of significant medical conditions as assessed by medical history, physical examination, and blood and urine tests. Volunteers will be randomly allocated to receive the Test Product under fasting or fed conditions.
There will be a minimum 23 calendar days washout between treatments. Blood samples will be collected at pre-dose (0 hours) and at 15 minutes, 30 minutes, 1 hour, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 96 hours and 120 hours post-dose (total: 21 samples per treatment period).
- Conditions
- Hereditary Tyrosinemia, Type I
- Being tested
- Nitisinone
- Keywords
- HT-1, Tyrosinemia, Nitisinone, Bioavailability, Healthy Volunteer, Food-Effect
- Medical subject headings
- Tyrosinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitisinoneDrug
A single oral dose of Nitisinone 10 mg Tablet will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence A (Fed) - B (Fasted) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fed conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone |
| Treatment Sequence B (Fasted) - A (Fed) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fasting conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fed conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax)
Measured: 0 - 120 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUC(0-120))
Measured: 0 - 120 hours post-dose
Secondary outcomes (5)
Area Under the Plasma Concentration Versus Time Curve (AUC(0-72))
Measured: 0 - 72 hours post-dose
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞))
Measured: 0 - 120 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax)
Measured: 0 - 120 hours post-dose
Terminal Elimination Rate Constant (λz)
Measured: 0 - 120 hours post-dose
Apparent Terminal Elimination Half-life (t1/2)
Measured: 0 - 120 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2016 (estimated)
- Study startNov 2015
- Primary completionDec 2015
- Study completionJan 2016
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 Hereditary Tyrosinemia, Type IStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cycle Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- André Nell, Principal investigator, +27 51 410 3046
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02750332
- Sponsor's protocol ID
- CT-002
- Other IDs
- PXL225421
- Status last verified
- Feb 2017
- First submitted
- 21 Apr 2016
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Single-Dose, Open-Label, Randomized Study to Compare the Bioavailability of an Oral Test Formulation Containing Nitisinone 10 mg in at Least 16 Healthy Male and Female Subjects Under Fasting and Fed Conditions
- ClinicalTrials.gov ID
- NCT02750332
- Acronym / sponsor ID
- CT-002
- Conditions
- Hereditary Tyrosinemia, Type I
- Keywords
- HT-1, Tyrosinemia, Nitisinone, Bioavailability, Healthy Volunteer, Food-Effect
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Cycle Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- Nov 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 25 Apr 2016 (estimated)
- Results
- Posted 13 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the bioavailability of the Test Product, Nitisinone 10 mg Tablet, under fasting and fed conditions (food-effect).
Detailed description
The specific aim is to conduct a randomized, single dose, two-period crossover bioavailability study in at least 16 healthy male and female subjects at a single study center to evaluate the in vivo performance of Test Product, Nitisinone 10 mg Tablet, under fasting and fed conditions.
The study in healthy male and female volunteers is designed to establish a pharmacokinetic (PK) profile under fed and fasting conditions for the orally administered Test Product, Nitisinone 10 mg Tablets.
A total of 20 healthy female and male volunteers (age 18 to 55 years old) will be entered into the study. Volunteers will be determined to be free of significant medical conditions as assessed by medical history, physical examination, and blood and urine tests. Volunteers will be randomly allocated to receive the Test Product under fasting or fed conditions.
There will be a minimum 23 calendar days washout between treatments. Blood samples will be collected at pre-dose (0 hours) and at 15 minutes, 30 minutes, 1 hour, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 96 hours and 120 hours post-dose (total: 21 samples per treatment period).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence A (Fed) - B (Fasted) | Experimental | Drug: NitisinoneSubjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fed conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence B (Fasted) - A (Fed) | Experimental | Drug: NitisinoneSubjects will receive a single 10 mg tablet of Nitisinone in treatment period 1 under fasting conditions, and 10 mg tablet of Nitisinone in treatment period 2 under fed conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy male and female subjects, 18 to 55 years (both inclusive) at signing of informed consent.
- Body Mass Index (BMI) between 18.5 and 30 kg/m2 (inclusive).
- Body mass not less than 50 kg.
- Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study.
- Non-smokers.
Key exclusion criteria (28 listed)
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
- Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females.
- Consumption of more than 5 cups of coffee (or equivalent amounts of caffeine) per day.
- Regular exposure to substances of abuse (other than alcohol) within the past year.
- Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks before the first administration of investigational medicinal product (IMP) except if this will not affect the outcome of the study in the opinion of the investigator.
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 |
|---|---|---|
| NitisinoneA single oral dose of Nitisinone 10 mg Tablet will be administered. | Drug | Treatment Sequence A (Fed) - B (Fasted), Treatment Sequence B (Fasted) - A (Fed) |
Primary outcome
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 - 120 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUC(0-120))
Time frame: 0 - 120 hours post-dose
5 secondary outcomes
Area Under the Plasma Concentration Versus Time Curve (AUC(0-72))
Time frame: 0 - 72 hours post-dose
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞))
Time frame: 0 - 120 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 - 120 hours post-dose
Terminal Elimination Rate Constant (λz)
Time frame: 0 - 120 hours post-dose
Apparent Terminal Elimination Half-life (t1/2)
Time frame: 0 - 120 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
André Nell principal investigator
+27 51 410 3046
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 in people with Hereditary Tyrosinemia, Type I, run by Cycle Pharmaceuticals Ltd. at 1 site in South Africa.
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 12 inclusion and 28 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 15 Mar 2017. 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 South Africa. 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 13 Dec 2016). 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?
Maximum Observed Plasma Concentration (Cmax) (time frame: 0 - 120 hours post-dose). 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 15 Mar 2017.