Hereditary Tyrosinemia, Type IPhase 1NCT02750709
Bioequivalence Study of Two Nitisinone Formulations Compared to Orfadin
A Phase 1 study testing Nitisinone, Nitisinone 10 mg Tablet High Compritol and Orfadin 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 determine whether Nitisinone 10 mg Tablets (Test Product 1 (TP1)) and Nitisinone 10 mg Tablets High Compritol (Test Product 2 (TP2)) are bioequivalent to the reference product Orfadin 10 mg capsules. 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, Nitisinone 10 mg Tablet High Compritol and Orfadin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSouth Africa
- Study dates
- Oct 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
- 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:
- Not of childbearing potential, e.g., has been surgically sterilized, undergone a hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal,
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- Note: In postmenopausal women, the value of the serum pregnancy test may be slightly increased. This test will be repeated to confirm the results. If there is no increase indicative of pregnancy, the female will be included in the study.
- OR
- 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 Investigational Medicinal Product (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.
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 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.
- 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.
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- 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, Laboratory-Blind, Randomized, Three-Period Crossover Study to Determine the Bioequivalence of Two Oral Formulations Containing of Nitisinone 10 mg Compared to the Reference Formulation Orfadin 10 mg in at Least 18 Healthy Male and Female Subjects Under Fasting Conditions
The purpose of this study is to determine whether Nitisinone 10 mg Tablets (Test Product 1 (TP1)) and Nitisinone 10 mg Tablets High Compritol (Test Product 2 (TP2)) are bioequivalent to the reference product Orfadin 10 mg capsules.
Read the detailed description
The specific aim is to conduct a randomized, single dose, three-period cross-over bioequivalence (BE) study in at least 18 healthy male and female subjects at a single study center to evaluate the in vivo performance of Nitisinone 10 mg Tablet (Test Product 1) and Nitisinone 10 mg Tablet High Compritol (Test Product 2) to the reference product Orfadin 10 mg capsules.
The pharmacokinetics (PK) of Test Product 1 and 2 compared to the reference product, will be determined and compared in healthy volunteers.
The modified version of Nitisinone Tablet (Test Product 2, higher glyceryl dibehenate (Compritol 888)) was administered to determine the acceptance limit of the dissolution profile for Nitisinone tablets with a longer dissolution time (Test Product 2) since the dissolution time of Nitisinone tablets (Test Product 1) lengthened over time under accelerated study conditions. The hypothesis is that should bioequivalence between Test Product 1 and Test Product 2 be demonstrated then it is concluded that the prolonged dissolution time had no impact on the bioequivalence of Nitisinone tablets.
A total of 24 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 one of the three treatment sequence groups and, on each occasion, receive one of the following: Nitisinone 10 mg Tablet, Nitisinone 10 mg High Compritol Tablet and Orfadin 10 mg hard capsules (reference listed drug, (RLD)). 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).
The primary endpoints will be the maximum blood concentration (Cmax) and the area under the curve (AUC) from time zero to 120 hours post-dose.
For the FDA, bioequivalence of the test and reference products will be assessed on the basis of the 90% confidence intervals for estimates of the geometric mean ratios between the primary PK parameters of the test and reference products using an analysis of variance considering the bioequivalence range of 80.00% to 125.00% for Cmax and AUC(0-120).
For Health Canada, bioequivalence of the test and reference products will be assessed on the basis of the 90% confidence interval for estimate of the geometric mean ratio between the primary PK parameter AUC(0-120) of the test and reference products using an analysis of variance considering the bioequivalence range of 80.00% to 125.00% and the point estimate of the geometric mean ratio of the primary PK parameter Cmax considering the bioequivalence range of 80.00% to 125.00%.
- Conditions
- Hereditary Tyrosinemia, Type I
- Being tested
- Nitisinone, Nitisinone 10 mg Tablet High Compritol, Orfadin
- Keywords
- HT-1, Tyrosinemia, Nitisinone, Bioequivalence, Healthy Volunteer, Orfadin
- 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 in fasted state.
Nitisinone 10 mg Tablet High CompritolDrug
A single oral dose of Nitisinone 10 mg High Compritol tablet will be administered in fasted state.
OrfadinDrug
A single oral dose of Orfadin 10 mg hard capsule will be administered in fasted state.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence A (TP 1) - B (TP 2) - C (Reference) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
| Treatment Sequence A (TP 1) - C (Reference) - B (TP 2) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 2) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
| Treatment Sequence B (TP 2) - A (TP 1) - C (Reference) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
| Treatment Sequence B (TP 2) - C (Reference) - A (TP 1) | Experimental | Subjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 3, and under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
| Treatment Sequence C (Reference) - A (TP 1) - B (TP 2) | Experimental | Subjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
| Treatment Sequence C (Reference) - B (TP 2) - A (TP 1) | Experimental | Subjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 2, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. Receives: Drug: Nitisinone; Drug: Nitisinone 10 mg Tablet High Compritol; Drug: Orfadin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax)
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Area Under the Plasma Concentration Versus Time Curve, From Time Zero to 120 Hours Post-dose (AUC(0-120))
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Secondary outcomes (5)
Area Under the Plasma Concentration Versus Time Curve, From Time Zero to 72 Hours Post-dose (AUC(0-72))
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72 hours post-dose
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞)
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Time to Maximum Observed Plasma Concentration (Tmax)
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Terminal Elimination Rate Constant (λz)
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Apparent Terminal Half-life (t1/2)
Measured: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
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 startOct 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
- 24 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, Bloemfontein Early Phase Clinical Unit, PAREXEL Internation (South Africa)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02750709
- Sponsor's protocol ID
- CT-001
- Other IDs
- PXL225418
- Status last verified
- Feb 2017
- First submitted
- 20 Apr 2016
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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, Laboratory-Blind, Randomized, Three-Period Crossover Study to Determine the Bioequivalence of Two Oral Formulations Containing of Nitisinone 10 mg Compared to the Reference Formulation Orfadin 10 mg in at Least 18 Healthy Male and Female Subjects Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT02750709
- Acronym / sponsor ID
- CT-001
- Conditions
- Hereditary Tyrosinemia, Type I
- Keywords
- HT-1, Tyrosinemia, Nitisinone, Bioequivalence, Healthy Volunteer, Orfadin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Cycle Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- Oct 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 determine whether Nitisinone 10 mg Tablets (Test Product 1 (TP1)) and Nitisinone 10 mg Tablets High Compritol (Test Product 2 (TP2)) are bioequivalent to the reference product Orfadin 10 mg capsules.
Detailed description
The specific aim is to conduct a randomized, single dose, three-period cross-over bioequivalence (BE) study in at least 18 healthy male and female subjects at a single study center to evaluate the in vivo performance of Nitisinone 10 mg Tablet (Test Product 1) and Nitisinone 10 mg Tablet High Compritol (Test Product 2) to the reference product Orfadin 10 mg capsules.
The pharmacokinetics (PK) of Test Product 1 and 2 compared to the reference product, will be determined and compared in healthy volunteers.
The modified version of Nitisinone Tablet (Test Product 2, higher glyceryl dibehenate (Compritol 888)) was administered to determine the acceptance limit of the dissolution profile for Nitisinone tablets with a longer dissolution time (Test Product 2) since the dissolution time of Nitisinone tablets (Test Product 1) lengthened over time under accelerated study conditions. The hypothesis is that should bioequivalence between Test Product 1 and Test Product 2 be demonstrated then it is concluded that the prolonged dissolution time had no impact on the bioequivalence of Nitisinone tablets.
A total of 24 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 one of the three treatment sequence groups and, on each occasion, receive one of the following: Nitisinone 10 mg Tablet, Nitisinone 10 mg High Compritol Tablet and Orfadin 10 mg hard capsules (reference listed drug, (RLD)). 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).
The primary endpoints will be the maximum blood concentration (Cmax) and the area under the curve (AUC) from time zero to 120 hours post-dose.
For the FDA, bioequivalence of the test and reference products will be assessed on the basis of the 90% confidence intervals for estimates of the geometric mean ratios between the primary PK parameters of the test and reference products using an analysis of variance considering the bioequivalence range of 80.00% to 125.00% for Cmax and AUC(0-120).
For Health Canada, bioequivalence of the test and reference products will be assessed on the basis of the 90% confidence interval for estimate of the geometric mean ratio between the primary PK parameter AUC(0-120) of the test and reference products using an analysis of variance considering the bioequivalence range of 80.00% to 125.00% and the point estimate of the geometric mean ratio of the primary PK parameter Cmax considering the bioequivalence range of 80.00% to 125.00%.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence A (TP 1) - B (TP 2) - C (Reference) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence A (TP 1) - C (Reference) - B (TP 2) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 2) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence B (TP 2) - A (TP 1) - C (Reference) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 2, and 10 mg hard capsule of Orfadin (Reference) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence B (TP 2) - C (Reference) - A (TP 1) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 1, 10 mg hard capsule of Orfadin (Reference) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 3, and under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence C (Reference) - A (TP 1) - B (TP 2) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 2, and 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 3 under fasting conditions. Each treatment period will be separated by at least 23 calendar days of washout period. |
| Treatment Sequence C (Reference) - B (TP 2) - A (TP 1) | Experimental | Drug: Nitisinone, Drug: Nitisinone 10 mg Tablet High Compritol, Drug: OrfadinSubjects will receive a single 10 mg hard capsule of Orfadin (Reference) in treatment period 1, 10 mg tablet of Nitisinone 10 mg Tablet High Compritol (Test Product 2) in treatment period 2, 10 mg tablet of Nitisinone 10 mg Tablet (Test Product 1) in treatment period 3 under fasting 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 (17 listed)
- 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:
Key exclusion criteria (27 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 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.
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 in fasted state. | Drug | Treatment Sequence A (TP 1) - B (TP 2) - C (Reference), Treatment Sequence A (TP 1) - C (Reference) - B (TP 2), Treatment Sequence B (TP 2) - A (TP 1) - C (Reference), Treatment Sequence B (TP 2) - C (Reference) - A (TP 1), Treatment Sequence C (Reference) - A (TP 1) - B (TP 2), Treatment Sequence C (Reference) - B (TP 2) - A (TP 1) |
| Nitisinone 10 mg Tablet High CompritolA single oral dose of Nitisinone 10 mg High Compritol tablet will be administered in fasted state. | Drug | Treatment Sequence A (TP 1) - B (TP 2) - C (Reference), Treatment Sequence A (TP 1) - C (Reference) - B (TP 2), Treatment Sequence B (TP 2) - A (TP 1) - C (Reference), Treatment Sequence B (TP 2) - C (Reference) - A (TP 1), Treatment Sequence C (Reference) - A (TP 1) - B (TP 2), Treatment Sequence C (Reference) - B (TP 2) - A (TP 1) |
| OrfadinA single oral dose of Orfadin 10 mg hard capsule will be administered in fasted state. | Drug | Treatment Sequence A (TP 1) - B (TP 2) - C (Reference), Treatment Sequence A (TP 1) - C (Reference) - B (TP 2), Treatment Sequence B (TP 2) - A (TP 1) - C (Reference), Treatment Sequence B (TP 2) - C (Reference) - A (TP 1), Treatment Sequence C (Reference) - A (TP 1) - B (TP 2), Treatment Sequence C (Reference) - B (TP 2) - A (TP 1) |
Primary outcome
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Area Under the Plasma Concentration Versus Time Curve, From Time Zero to 120 Hours Post-dose (AUC(0-120))
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
5 secondary outcomes
Area Under the Plasma Concentration Versus Time Curve, From Time Zero to 72 Hours Post-dose (AUC(0-72))
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72 hours post-dose
Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞)
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Terminal Elimination Rate Constant (λz)
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
Apparent Terminal Half-life (t1/2)
Time frame: 0, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours
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.
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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
Bloemfontein Early Phase Clinical Unit, PAREXEL Internation (South Africa)
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, Nitisinone 10 mg Tablet High Compritol and Orfadin 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 17 inclusion and 27 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, 0.25, 0.50, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours). 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.