Bioequivalence Study of Two Nitisinone Formulations Compared to Orfadin

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02750709
• Date of registration: 20/04/2016
• Prospective Registration: No
• Primary sponsor: Cycle Pharmaceuticals Ltd.
• Public title: Bioequivalence Study of Two Nitisinone Formulations Compared to Orfadin
• Scientific 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
• Date of first enrolment: October 2015
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02750709
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

South Africa

Contacts

• Name: André Nell
• Affiliation: Bloemfontein Early Phase Clinical Unit, PAREXEL Internation (South Africa)

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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,

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.

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 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).



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hereditary Tyrosinemia, Type I

Intervention(s)

Drug: Nitisinone

Drug: Nitisinone 10 mg Tablet High Compritol

Drug: Orfadin

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

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(0-8) [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 (?z) [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]

Secondary ID(s)

PXL225418

CT-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Parexel

Results

• Results available: Yes
• Date Posted: 13/12/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02750709