Riluzole Orodispersible Film Replicate Bioavailability

NCT04819438 | Completed Phase 1 Results

• 1 other identifier: Z7251J01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to compare the pharmacokinetic profile of riluzole after replicate single dose of the novel orodispersible film test formulation and of the marketed reference Rilutek® tablets and to evaluate their bioequivalence.

Conditions

Healthy Participants

Keywords

Bioequivalence; Riluzole; Orodispersible film

Outcome Measures

Primary Outcomes (2)

• Evaluation of the Bioequivalent Rate of Absorption (Cmax) of Riluzole After Replicate Single Dose Administration of Test and Reference

  For each individual, the maximum plasma concentration (Cmax) of riluzole after replicate single dose administration of Test and Reference was measured. The Cmax 90% confidence interval of the ratio Test/Reference of the population means was calculated. The bioequivalence is demonstrated when the 90% confidence Interval of this ratio lies within the range 80.00-125.00% (acceptance interval).

  0 h (pre-dose) and 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after the drug administration

• Evaluation of the Bioequivalent Extent of Absorption (AUC0-t) of Riluzole After Replicate Single Dose Administration of Test and Reference.

  For each individual, the area under the concentration-time curve from single dose Test and Reference administration to the last observed concentration time t (AUC0-t) of riluzole was measured. The AUC0-t 90% confidence interval of the ratio Test/Reference of the population means was calculated. The bioequivalence is demonstrated when the 90% confidence Interval of this ratio lies within the range 80.00-125.00% (acceptance interval).

  0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration

Secondary Outcomes (7)

• To Describe the t1/2 (Half-life) of Riluzole After Replicate Single Dose Administration of Test and Reference

  0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration

• To Describe the AUC0-∞ of Riluzole After Replicate Single Dose Administration of Test and Reference

  0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration

• Description Tmax: Time to Achieve Cmax Reference

  0 h (pre-dose), 15, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h after drug administration

• Evaluation of the Test Product Palatability

  Immediately after 1st Test product administration, approximately within 5 minutes after administration

• Evaluation of the Test Product Palatability

  Immediately after 2nd Test product administration, approximately within 5 minutes after administration

Study Arms (2)

Reference/Test/Reference/Test

EXPERIMENTAL

Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.

Drug: Riluzole 50 mg orodispersible film; Drug: Rilutek® 50 mg riluzole tablets

Test/Reference/Test/Reference

EXPERIMENTAL

Riluzole orodispersible film (test): The subjects will be treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek® (reference): The subjects will be treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.

Drug: Riluzole 50 mg orodispersible film; Drug: Rilutek® 50 mg riluzole tablets

Interventions

Riluzole 50 mg orodispersible film DRUG

Before each administration, the subjects will drink 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy will take the orodispersible film (32.0x22.0 mm) out of the provided pouch and place the product directly on the top surface (dorsal aspect) of the subjects' tongue.

Also known as: Test product (T)

Reference/Test/Reference/Test; Test/Reference/Test/Reference

Rilutek® 50 mg riluzole tablets DRUG

One film-coated tablet will be swallowed (without chewing) with 150 mL of still mineral water.

Also known as: Reference product (R)

Reference/Test/Reference/Test; Test/Reference/Test/Reference

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex and Age: men/women, 18-55 years old inclusive
• Tobacco: non-smokers for at least 6 months prior to study screening
• Body Mass Index (BMI): 18.5-29 kg/m2 inclusive
• Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
• Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception:
• A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
• A male sexual partner who agrees to use a male condom with spermicide
• A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, pregnancy test result must be negative at screening.

You may not qualify if:

• Electrocardiogram (ECG) 12-leads: (supine position) clinically significant abnormalities; corrected QT interval \> 450 msec
• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
• Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
• Cotinine: positive cotinine test at screening
• Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
• Diseases: clinically significant history or presence of renal, hepatic, gastrointestinal, cardiovascular, cerebrovascular, immunological, musculoskeletal, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases or surgeries that may interfere with the aim of the study. Gastrointestinal pathologies include any clinically significant disorder of the mouth, e.g. impairment of swallowing, lesions, ulcerations, deformities, untreated dental caries
• Dentures: presence of mouth jewellery, dentures, braces, piercings that may interfere with successful completion of the dosing
• Medications: medications, including over the counter medications and herbal remedies for 2 weeks before study screening; central nervous system depressants, including opioids, benzodiazepines, general anaesthetics and anticonvulsants, or cytochrome C inhibitors, including cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and antiretroviral agents, or strong cytochrome C inducers, including barbiturates, carbamazepine, glucocorticoids, phenytoin, St John's wort and rifampin, or hormonal oral or transdermal contraceptives for 30 days before study screening; implanted, injected, intravaginal or intrauterine hormonal contraceptives for 6 months before study screening
• Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
• Blood donation: blood donations for 3 months before this study
• Drug, alcohol, caffeine, tobacco: history of drug, alcohol \[\>1 drink/day for females and \>2 drinks/day for males, defined according to the Dietary Guidelines 2015 \], caffeine (\>5 cups coffee/tea/day) or tobacco use including any tobacco product like e-cigarettes and vamping products
• Drug test: positive result at the drug test at screening or Day -1
• Alcohol test: positive alcohol breath test at Day -1
• Diet: abnormal diets (\<1600 or \>3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians and vegans
• Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women

Sponsors & Collaborators

• Cross Research S.A.: lead
• Zambon SpA: collaborator

Study Sites (1)

CROSS Research SA Phase 1 Unit

Arzo, Canton Ticino, 6864, Switzerland

Location

MeSH Terms

Interventions

Riluzole

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Mathias Knecht, Chief Medical Officer
• Organization: Zambon S.p.A.

mathias.knecht@zambongroup.com

+41.91.960.4187

Study Officials

• Milko Radicioni, MD

  CROSS Research SA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study was designed in agreement with the EMA guideline "Guidance on the investigation of bioequivalence", CPMP/EWP/QWP/1401/98 Rev. 1 January 2010 (9).

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 29, 2021
• Study Start: January 15, 2021
• Primary Completion: March 14, 2021
• Study Completion: March 14, 2021
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)