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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03757338




Registration number
NCT03757338
Ethics application status
Date submitted
27/11/2018
Date registered
28/11/2018
Date last updated
29/11/2018

Titles & IDs
Public title
Bioequivalence Study of a Test Capsule Formulation of Fingolimod With the Reference Capsule Formulation of Fingolimod
Scientific title
A Randomized, Single Dose, Crossover, Bioequivalence Study of Fingolimod 0.5 mg Capsule (Asofarma S.A.I. y C., Argentina) Compared With Gilenya 0.5 mg Capsule (Novartis Pharmaceuticals, Australia Pty Ltd) in Fasting Healthy Subjects
Secondary ID [1] 0 0
ZPS-578 (C15-020-LBB)
Secondary ID [2] 0 0
ACTRN12615001055594
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fingolimod Reference Formulation
Treatment: Drugs - Fingolimod Test Formulation

Active Comparator: Fingolimod Reference Formulation - 0.5 mg Fingolimod capsule (manufactured by Novartis, Batch No. S0099), orally administered as a single dose of 3 x 0.5 mg capsules.

Experimental: Fingolimod Test Formulation - 0.5 mg Fingolimod capsule (manufactured by manufactured by Asofarma S.A.I. y C. on behalf of Tolmar, Batch No. 22264), orally administered as a single dose of 3 x 0.5 mg capsules.


Treatment: Drugs: Fingolimod Reference Formulation
To compare the rate and extent of absorption for Fingolimod when administered as a single oral dose of 3 x 0.5 mg capsules of the reference product produced by Novartis Pharmaceutical with the proposed test product manufactured by Asofarma S.A.I. y C. in healthy volunteers, under fasted conditions.

Treatment: Drugs: Fingolimod Test Formulation
To compare the rate and extent of absorption for Fingolimod when administered as a single oral dose of 3 x 0.5 mg capsules of the proposed test product manufactured by Asofarma S.A.I. y C. with the reference product produced by Novartis Pharmaceutical in healthy volunteers, under fasted conditions.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Fingolimod plasma Cmax (maximum plasma concentration) when administered as a single oral dose of 3 x 0.5 mg capsule of the test versus reference product. - Fingolimod plasma Cmax will be calculated based on plasma Fingolimod concentrations within 1 hour pre-dose (time 0) and at 1, 2, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24, 32, 48, 56 and 72 hours post-dose.
Timepoint [1] 0 0
Measurement within 72 hours post-dose.
Primary outcome [2] 0 0
Fingolimod AUC0-t (area under the plasma concentration-time curve from time of intake until the last quantifiable concentration) when administered as a single oral dose of 3 x 0.5 mg capsule of the test versus reference product. - Fingolimod AUC0-t will be calculated based on plasma Fingolimod concentrations within 1 hour pre-dose (time 0) and at 1, 2, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24, 32, 48, 56 and 72 hours post-dose.
Timepoint [2] 0 0
Measurement within 72 hours post-dose.
Primary outcome [3] 0 0
Fingolimod AUC0-8 (area under the plasma concentration-time curve from time of intake until infinity) when administered as a single oral dose of 3 x 0.5 mg capsule of the test versus reference product. - Fingolimod AUC0-8 will be calculated based on plasma Fingolimod concentrations within 1 hour pre-dose (time 0) and at 1, 2, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24, 32, 48, 56 and 72 hours post-dose.
Timepoint [3] 0 0
Measurement within 72 hours post-dose.
Secondary outcome [1] 0 0
Fingolimod elimination t1/2 (elimination half-life), when administered as a single oral dose of 3 x 0.5 mg capsule of the test versus reference product. - Fingolimod t1/2 will be calculated based on plasma Fingolimod concentrations within 1 hour pre-dose (time 0) and at 1, 2, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24, 32, 48, 56 and 72 hours post-dose.
Timepoint [1] 0 0
Measurement within 72 hours post-dose.
Secondary outcome [2] 0 0
Fingolimod Tmax (time to Cmax), when administered as a single oral dose of 3 x 0.5 mg capsule of the test versus reference product. - Fingolimod Tmax will be calculated based on plasma Fingolimod concentrations within 1 hour pre-dose (time 0) and at 1, 2, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24, 32, 48, 56 and 72 hours post-dose.
Timepoint [2] 0 0
Measurement within 72 hours post-dose.

Eligibility
Key inclusion criteria
- Written informed consent for the participation in the study.

- Aged between 18 and 45 years, inclusive.

- All females of childbearing potential must have a negative serum pregnancy test 3 days
prior to dosing in both study periods.

- Females of childbearing potential must agree to acceptable method of contraception (as
agreed with the study doctor) or abstain from sexual activity during the study.

- Body Mass Index (BMI) within 18 - 30 kg/m2, inclusive, with body mass above 45 kg.

- Normal, healthy individuals as determined by medical history, physical examination,
vital signs, ECG and laboratory tests.

- Non-smoker (for at least 6 months). This includes all tobacco products and nicotine
containing patches and gums.

- Must abstain from consuming alcohol and caffeine and remain chocolate free for 48
hours prior to the study and throughout each study period (i.e. until 72 hours
post-dosing in each period).

- Non-consumption of grapefruits or oranges, grapefruit and/or orange juice and any
grapefruit and/or orange products for 1 week prior to the study and throughout the
study (i.e. until 72 hours after receiving the final dose).

- Subjects must agree and be able to follow the study procedures, in the Investigator's
opinion.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known hypersensitivity to fingolimod, its analogues or excipients of the tested drug
or the reference drug, lactose malabsorption, glucose-galactose malabsorption or Lapp
lactase deficiency.

- Aggravated history of allergies (evidence of anaphylactic shock or Quincke's edema).

- History of gastrointestinal (GI), hepatic or renal abnormality or any other
abnormality, which, in the Investigator's opinion, may affect absorption,
distribution, metabolism and excretion of the IMPs (e.g. operative interventions to
the GI tract other than appendectomy).

- Pregnant or breastfeeding females.

- Acute infectious diseases within 4 weeks before the study start.

- Significant cardio-vascular, pulmonary, hematologic, neurologic, psychiatric,
endocrine, immunologic, ophthalmologic or dermatologic disease.

- Subjects who have had any severe eye problems or conditions especially inflammation of
the eye, such as uveitis.

- Vital signs measured in the seated position: heart rate <50 or >90 beats per minute or
systolic BP <90 mmHg or >160 mmHg or diastolic BP <50 mmHg or >90 mmHg.

- Subjects with prolonged QTc interval (defined as >450 msec for males and >470 msec for
females).

- Any clinically significant laboratory abnormalities at screening, including potassium,
bilirubin, asparte transaminase (AST) and alanine transaminase (ALT) blood levels.

- Evidence of routine consumption of more than 10 units of alcohol per week within 6
months before screening (1 unit of alcohol is equivalent to 500 ml of beer, 200 ml of
wine or 50 ml of spirit), positive breath test for alcohol or alcohol consumption
within 48 hours prior to the study start.

- Evidence of any drug abuse within one year prior to the study start or positive urine
drug and prohibited medication screen.

- Concomitant drug therapy of any kind with the exception of prescribed hormonal
contraceptives.

- Having received vaccinations within 1 month prior to dosing or any planned vaccination
within 2 months of the last dose of fingolimod.

- Administration of any medication that can cause a significant effect onto hemodynamics
or liver function within 30 days prior to the study start.

- Administration of any medications which can induce or inhibit the drug hepatic
metabolism via CYP1A2, CYP2D6, CYP2C8, CYP3A4 and CYP17 (hepatic metabolism inducers
include barbiturates, carbamazepine, phenytoin, glucocorticosteroids, omeprazole;
hepatic metabolism inhibitors include antidepressants, cimetidine, diltiazem,
macrolides, imidazole, neuroleptics, verapamil, fluoroquinolones, antihistamine
drugs), as well as herbal preparations and extracts within 30 days prior to the study
start.

- Administration of any injectable deposit (sustained release) formulations or drug
implants within 3 months prior to the study drug administration.

- Participation in any clinical study within 60 days prior to the study start.

- Donation or loss of more than 450 ml of blood within 2 months prior to the screening
visit.

- Possible difficulties with study drug swallowing.

- History of tuberculosis or participation in the tuberculosis control program.

- Herpes simplex or varicella zoster virus infection including cold sore, genital
herpes, chickenpox or shingles.

- Human Immunodeficiency Virus (HIV) positive test, positive test for hepatitis B or C.

- Other acute or chronic medical or mental conditions, laboratory abnormalities which
may increase risk associated with the study participation or with study drug
administration or which may affect interpretation of the study results and, in the
Investigator's opinion, make the subject non-eligible for participation in this study.

- Inability of the subject to follow the requirements of the study.

- Employees of the study Sponsor.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Dunedin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Asofarma S.A.I. y C.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Zenith Technology Corporation Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The study evaluates the bioequivalence of the Test formulation, 0.5 mg Fingolimod HCl capsule
(Asofarma S.A.I. y C. on behalf of Tolmar, Batch No. 22264), relative to that of the
Reference formulation, 0.5 mg Gilenya® (fingolimod) capsule (Novartis Pharmaceuticals, Batch
No. S0099), following oral administration of a single oral dose of 3 x 0.5 mg in healthy,
adult, male and female subjects under fasting conditions.
Trial website
https://clinicaltrials.gov/show/NCT03757338
Trial related presentations / publications
Food and Drug Administration, USA. Bioequivalence Recommendations for fingolimod, Aug 2011.
Australian Product Information, Gilenya, 1 April 2015
Public notes

Contacts
Principal investigator
Name 0 0
Noelyn A Hung, MB ChB
Address 0 0
Zenith Technology Corporation Ltd, 156 Frederick Street, Dunedin, New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications