Trial Outcomes & Findings for Riluzole Orodispersible Film Replicate Bioavailability (NCT NCT04819438)

NCT ID: NCT04819438

Last Updated: 2025-05-02

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 54 participants
• Primary outcome timeframe: 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
• Results posted on: 2025-05-02

Participant Flow

Participants were recruited at the Phase I Unit from January 2021 to February 2021.

Fifty-four (54) subjects were randomised in the study and 53 of them received at least one dose of investigational product, while one subject discontinued the study before receiving any treatment due to adverse event.

Participant milestones

Measure	Riluzole 50mg (Test) / Rilutek 50mg (Reference) / Riluzole 50mg (Test) / Rilutek 50mg (Reference) Riluzole 50 mg Orodispersible Film (Test, T): The subjects were treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. Before each administration, the subjects drank 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy took the orodispersible film (32.0x22.0 mm) out of the provided pouch and placed the product directly on the top surface (dorsal aspect) of the subjects' tongue. Rilutek 50 mg Tablet (Reference, R): The subjects were treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. One film-coated tablet was swallowed (without chewing) with 150 mL of still mineral water.	Rilutek 50mg (Reference) / Riluzole 50mg (Test) / Rilutek 50mg (Reference) / Riluzole 50mg (Test) Riluzole 50 mg Orodispersible Film (Test, T): The subjects were treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. Before each administration, the subjects drank 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy took the orodispersible film (32.0x22.0 mm) out of the provided pouch and placed the product directly on the top surface (dorsal aspect) of the subjects' tongue. Rilutek 50 mg Tablet (Reference, R): The subjects were treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. One film-coated tablet was swallowed (without chewing) with 150 mL of still mineral water.
Overall Study STARTED	27	27
Overall Study COMPLETED	26	25
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Riluzole 50mg (Test) / Rilutek 50mg (Reference) / Riluzole 50mg (Test) / Rilutek 50mg (Reference) Riluzole 50 mg Orodispersible Film (Test, T): The subjects were treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. Before each administration, the subjects drank 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy took the orodispersible film (32.0x22.0 mm) out of the provided pouch and placed the product directly on the top surface (dorsal aspect) of the subjects' tongue. Rilutek 50 mg Tablet (Reference, R): The subjects were treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. One film-coated tablet was swallowed (without chewing) with 150 mL of still mineral water.	Rilutek 50mg (Reference) / Riluzole 50mg (Test) / Rilutek 50mg (Reference) / Riluzole 50mg (Test) Riluzole 50 mg Orodispersible Film (Test, T): The subjects were treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. Before each administration, the subjects drank 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy took the orodispersible film (32.0x22.0 mm) out of the provided pouch and placed the product directly on the top surface (dorsal aspect) of the subjects' tongue. Rilutek 50 mg Tablet (Reference, R): The subjects were treated with one film-coated tablet containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. One film-coated tablet was swallowed (without chewing) with 150 mL of still mineral water.
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	0	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

Riluzole Orodispersible Film Replicate Bioavailability

Baseline characteristics by cohort

Measure	All Study Participants n=54 Participants 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. The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence. The subjects received single oral doses of 50 mg of riluzole, as test orodispersible film and reference film-coated tablets under fasting conditions, in each of 4 subsequent periods separated by wash-out intervals of at least 7 days between consecutive administrations, according to a 2-treatment, 4-period, replicate cross-over design.
Age, Continuous	40.3 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Switzerland	54 participants n=5 Participants
Body weight	65.86 kilograms STANDARD_DEVIATION 10.87 • n=5 Participants
Height	167.8 centimeters STANDARD_DEVIATION 8.9 • n=5 Participants
Body mass index	23.30 kilograms/square meters STANDARD_DEVIATION 2.65 • n=5 Participants

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) n=51 Participants The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Evaluation of the Bioequivalent Rate of Absorption (Cmax) of Riluzole After Replicate Single Dose Administration of Test and Reference	315.62 ng/mL Standard Deviation 124.95	278.81 ng/mL Standard Deviation 123.32

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) n=51 Participants The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Evaluation of the Bioequivalent Extent of Absorption (AUC0-t) of Riluzole After Replicate Single Dose Administration of Test and Reference.	1263.40 h*ng/mL Standard Deviation 571.58	1135.98 h*ng/mL Standard Deviation 514.98

SECONDARY outcome

Timeframe: 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 half-life of riluzole, calculated, if feasible, as ln2/λz, After Replicate Single Dose Administration of Test and Reference.

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) n=51 Participants The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
To Describe the t1/2 (Half-life) of Riluzole After Replicate Single Dose Administration of Test and Reference	10.22 h Standard Deviation 1.66	10.22 h Standard Deviation 1.48

SECONDARY outcome

Timeframe: 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

For each individual, the area under the concentration-time curve extrapolated to infinity after single dose administration of Test and Reference (AUC0-∞) was measured. The AUC0-∞ 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).

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) n=51 Participants The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
To Describe the AUC0-∞ of Riluzole After Replicate Single Dose Administration of Test and Reference	1348.31 h*ng/mL Standard Deviation 630.80	1207.79 h*ng/mL Standard Deviation 566.13

SECONDARY outcome

Timeframe: 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

The results will be displayed and summarised in tables and figures.

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) n=51 Participants The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Description Tmax: Time to Achieve Cmax Reference	0.75 h Interval 0.25 to 2.0	0.75 h Interval 0.25 to 4.0

SECONDARY outcome

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

Population: Data for this outcome measure were only collected after administration of the Test product (Riluzole orodispersible film). The overall number of participants analyzed is the number of subjects who received Riluzole 50 mg orodispersible film (T) at the 1st administration.

Palatability was scored according to the following scale. Palatability evaluation description and scores (between brackets): Very unpleasant (0), Unpleasant (1), Acceptable (2), Good (3), Very good (4).

Minimun value is 0, maximum value is 4. An higher score mean a better outcome.

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=52 Participants 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® Tablet (Reference) The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Evaluation of the Test Product Palatability 0 - very unpleasant	0 Participants	—
Evaluation of the Test Product Palatability 1 - unpleasant	1 Participants	—
Evaluation of the Test Product Palatability 2 - acceptable	15 Participants	—
Evaluation of the Test Product Palatability 3 - good	31 Participants	—
Evaluation of the Test Product Palatability 4 - very good	5 Participants	—

SECONDARY outcome

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

Population: Data for this outcome measure were only collected after administration of the Test product (Riluzole orodispersible film). The overall number of participants analyzed is the number of subjects who received Riluzole 50 mg orodispersible film (T) at the 2nd administration.

Palatability was scored according to the following scale. Palatability evaluation description and scores (between brackets): Very unpleasant (0), Unpleasant (1), Acceptable (2), Good (3), Very good (4).

Minimun value is 0, maximum value is 4. An higher score mean a better outcome.

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=51 Participants 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® Tablet (Reference) The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Evaluation of the Test Product Palatability 0 - very unpleasant	0 Participants	—
Evaluation of the Test Product Palatability 1 - unpleasant	2 Participants	—
Evaluation of the Test Product Palatability 2 - acceptable	14 Participants	—
Evaluation of the Test Product Palatability 3 - good	28 Participants	—
Evaluation of the Test Product Palatability 4 - very good	7 Participants	—

SECONDARY outcome

Timeframe: pre-dose (0), 0.5 and 1 h after the drug administration

Population: Data for this outcome measure were only collected for the Test product (Riluzole orodispersible film). No mouth inspection was performed after Reference (Rilutek®) administration. The overall number of participants analyzed is the number of subjects who received Riluzole 50 mg orodispersible film (T).

Mouth inspections were performed before the Test administration and 30 min and 1 h after administrations of Test, to check the mucosal irritation at the application site. The outcome number shows the overall number of subjects with mucosal irritation.

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=52 Participants 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® Tablet (Reference) The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Number of Participants With Mucosal Irritation	0 Participants	—

SECONDARY outcome

Timeframe: At screening (initial visit) and at final visit (approximately 1 month)

Overall investigator's interpretation (as normal or abnormal and, if abnormal, clinically significant or not clinically significant).

The following analyses were performed at screening: Leukocytes, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, thrombocytes, electrolytes, enzymes (alkaline phosphatase, γ-GT, AST, ALT), total bilirubin, creatinine, glucose, urea, uric acid, total cholesterol, triglycerides, cotinine, total proteins. Serum pregnancy test (women). Urine analysis: pH, specific weight, appearance, colour, nitrites, proteins, glucose, urobilinogen, bilirubin, ketones, haematic pigments, leukocytes. Urine sediment (analysis performed only if positive): leukocytes, erythrocytes, flat cells, round cells, crystals, cylinders, mucus, bacteria. Hepatitis B (HBs antigen), Hepatitis C (HCV antibodies), HIV 1/2 (HIV Ag/Ab combo).

The same analyses, with the exception of cotinine, urine drug test, virology and pregnancy test, were performed at the final visit

Outcome measures

Measure	Riluzole Orodispersible Film (Test) n=53 Participants 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® Tablet (Reference) The subjects will be treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence.
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Screening visit · Normal	3 Participants	—
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Screening visit · Abnormal, Not Clinically Significant	50 Participants	—
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Screening visit · Abnormal, Clinically Significant	0 Participants	—
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Final visit (approximately 1 month) · Normal	1 Participants	—
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Final visit (approximately 1 month) · Abnormal, Not Clinically Significant	52 Participants	—
Haematology, Blood Chemistry and Urinalysis Laboratory Tests Interpretation Final visit (approximately 1 month) · Abnormal, Clinically Significant	0 Participants	—

Adverse Events

Riluzole Orodispersible Film (Test)

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

Rilutek® (Reference)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Riluzole Orodispersible Film (Test) n=52 participants at risk The subjects were treated with one orodispersible film containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Riluzole 50 mg Oral Film: Before each administration, the subjects drank 20 mL of still mineral water in order to wet their mouth. Afterwards, using gloves, the investigator or deputy took the orodispersible film (32.0x22.0 mm) out of the provided pouch and placed the product directly on the top surface (dorsal aspect) of the subjects' tongue.	Rilutek® (Reference) n=53 participants at risk The subjects were treated with one film-coated table containing 50 mg of riluzole in two out of the four study periods according to the randomisation sequence Rilutek 50Mg Tablet: One film-coated tablet was swallowed (without chewing) with 150 mL of still mineral water.
Gastrointestinal disorders Hypoaesthesia oral	100.0% 52/52 • Number of events 102 • 36 days	0.00% 0/53 • 36 days
Nervous system disorders Headache	21.2% 11/52 • Number of events 15 • 36 days	26.4% 14/53 • Number of events 15 • 36 days

Additional Information

Dr. Mathias Knecht, Chief Medical Officer

Zambon S.p.A.

Phone: +41.91.960.4187

Email: mathias.knecht@zambongroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place