- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02750332
Bioavailability Food-Effect Study of an Oral Nitisinone Formulation to Treat Hereditary Tyrosinemia (HT-1)
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Free State
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Bloemfontein, Free State, South Africa, 9301
- Bloemfontein Early Phase Clinical Unit, PAREXEL International (South Africa)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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:
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.
Exclusion Criteria:
- 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.
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Treatment Sequence A (Fed) - B (Fasted)
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.
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A single oral dose of Nitisinone 10 mg Tablet will be administered.
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Experimental: Treatment Sequence B (Fasted) - A (Fed)
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.
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A single oral dose of Nitisinone 10 mg Tablet will be administered.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Maximum Observed Plasma Concentration (Cmax)
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Area Under the Plasma Concentration Versus Time Curve (AUC(0-120))
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area Under the Plasma Concentration Versus Time Curve (AUC(0-72))
Time Frame: 0 - 72 hours post-dose
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0 - 72 hours post-dose
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Area Under the Plasma Concentration Versus Time Curve, With Extrapolation to Infinity (AUC(0-∞))
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Time to Maximum Observed Plasma Concentration (Tmax)
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Terminal Elimination Rate Constant (λz)
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Apparent Terminal Elimination Half-life (t1/2)
Time Frame: 0 - 120 hours post-dose
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0 - 120 hours post-dose
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: André Nell, +27 51 410 3046
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Amino Acid Metabolism, Inborn Errors
- Tyrosinemias
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Nitisinone
Other Study ID Numbers
- CT-002
- PXL225421 (Other Identifier: PAREXEL)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hereditary Tyrosinemia, Type I
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Cycle Pharmaceuticals Ltd.ParexelCompletedHereditary Tyrosinemia, Type ISouth Africa
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Swedish Orphan BiovitrumCompletedEfficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1 (HT-1)Hereditary Tyrosinemia, Type IBelgium, Denmark, France, Germany, Sweden
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Yassin Abdelghaffar Charity Center for Liver Disease...Society of Friends of Liver Patients in the Arab World (SLPAW)RecruitingHereditary Tyrosinemia, Type IEgypt
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Swedish Orphan BiovitrumCompletedHereditary Tyrosinemia, Type IGermany, United Kingdom, France
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Swedish Orphan BiovitrumCompletedHereditary Tyrosinemia, Type IBelgium, Denmark, France, Germany, Austria, Czechia, Finland, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom
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Cycle Pharmaceuticals Ltd.ParexelCompletedHereditary Tyrosinemia, Type ISouth Africa
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Vitaflo International, LtdCompletedAlkaptonuria | Tyrosinemias | Tyrosinemia, Type I | Tyrosinemia, Type II | Tyrosinemia, Type IIIUnited Kingdom
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Swedish Orphan BiovitrumRecruitingHereditary Tyrosinemia, Type IChina
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metaX Institut fuer Diatetik GmbHGreat Ormond Street Hospital for Children NHS Foundation Trust; Birmingham...Not yet recruitingAlkaptonuria | Homocystine; Metabolic Disorder | Tyrosinemia, Type I | Tyrosinemia, Type II | Tyrosinemia, Type III | MSUD (Maple Syrup Urine Disease)
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Sutphin DrugsUnknownHereditary Tyrosinemia, Type IIndia
Clinical Trials on Nitisinone
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Swedish Orphan BiovitrumCompleted
-
Cycle Pharmaceuticals Ltd.ParexelCompletedHereditary Tyrosinemia, Type ISouth Africa
-
Swedish Orphan BiovitrumCompleted
-
National Human Genome Research Institute (NHGRI)Completed
-
University of FloridaCompleted
-
Cycle Pharmaceuticals Ltd.ParexelCompletedHereditary Tyrosinemia, Type ISouth Africa
-
Swedish Orphan BiovitrumCompletedHereditary Tyrosinemia, Type IGermany, United Kingdom, France
-
Sutphin DrugsUnknownHereditary Tyrosinemia, Type IIndia
-
Swedish Orphan BiovitrumCompletedHereditary Tyrosinemia, Type IBelgium, Denmark, France, Germany, Austria, Czechia, Finland, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, United Kingdom
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National Eye Institute (NEI)National Human Genome Research Institute (NHGRI)Completed