Bioequivalence Study of a Test Capsule Formulation of Fingolimod With the Reference Capsule Formulation of Fingolimod

NCT03757338 | Completed Phase 1

• 2 other identifiers: ACTRN12615001055594ZPS-578 (C15-020-LBB)
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• 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.

  Measurement within 72 hours post-dose.

• 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.

  Measurement within 72 hours post-dose.

• Fingolimod AUC0-∞ (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-∞ 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.

  Measurement within 72 hours post-dose.

Secondary Outcomes (2)

• 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.

  Measurement within 72 hours post-dose.

• 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.

  Measurement within 72 hours post-dose.

Other Outcomes (5)

• Fingolimod Phosphate 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.

  Measurement within 72 hours post-dose.

• Fingolimod Phosphate 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.

  Measurement within 72 hours post-dose.

• Fingolimod Phosphate AUC0-∞ (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.

  Measurement within 72 hours post-dose.

Study Arms (2)

Fingolimod Reference Formulation

ACTIVE COMPARATOR

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

Drug: Fingolimod Reference Formulation

Fingolimod Test Formulation

EXPERIMENTAL

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.

Drug: Fingolimod Test Formulation

Interventions

Fingolimod Reference Formulation DRUG

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.

Also known as: Gylenia®

Fingolimod Reference Formulation

Fingolimod Test Formulation DRUG

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.

Also known as: Lebrina®

Fingolimod Test Formulation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asofarma S.A.I. y C.: lead
• Zenith Technology Corporation Limited: collaborator

Study Sites (1)

Zenith Clinical Site

Dunedin, 9010, New Zealand

Location

Related Publications (3)

• Food and Drug Administration, USA. Bioequivalence Recommendations for fingolimod, Aug 2011.

  BACKGROUND

• Australian Product Information, Gilenya, 1 April 2015

  BACKGROUND

• Hung NA, Costa FG, Hung CT, Rosenberg ME. Bioequivalence Study of 2 Capsule Formulations of Fingolimod 0.5 mg Assessing Both Parent Drug and Active Metabolite in New Zealand Healthy Subjects (Truncated Design). Clin Pharmacol Drug Dev. 2020 Jul;9(5):610-620. doi: 10.1002/cpdd.813. Epub 2020 May 28.

  PMID: 32468719 DERIVED

Study Officials

• Noelyn A Hung, MB ChB

  Zenith Technology Corporation Ltd, 156 Frederick Street, Dunedin, New Zealand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study was conducted as a blinded study regarding dose administration and sample collection. In addition, the blood samples from each subject were coded in a manner to make the analyst blind to the identity of the samples, allowing efficient conduct of the analytical procedure.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single centre, single dose, blinded, two treatment, two period, two sequence, two-way crossover, randomized study.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: October 23, 2015
• Primary Completion: January 26, 2016
• Study Completion: January 26, 2016
• Last Updated: November 29, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)