Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000112369
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
8/01/2026
Date registered
Help: Date registered
29/01/2026
Date last updated
Help: Date last updated
23/06/2026
Date data sharing statement initially provided
Help: Data sharing statement date
29/01/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
A Multicenter, Randomized, Fixed Sequence, Cross-over Study to Assess the Safety, Tolerability, and Pharmacokinetics of MRX-4TZT TDS (Tizanidine Transdermal Delivery System) versus Oral Tizanidine in Multiple Sclerosis Patients with Established Spasticity
Scientific title
A Multicenter, Randomized, Fixed Sequence, Cross-over Study to Assess the Safety, Tolerability, and Pharmacokinetics of MRX-4TZT TDS (Tizanidine Transdermal Delivery System) versus Oral Tizanidine in Multiple Sclerosis Patients with Established Spasticity
Additional trial identifiers [1] 315891 0
MRX-4TZT-05
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Multiple Sclerosis 339669 0
Spasticity 340383 0
Condition category
Condition code
Neurological 335900 335900 0 0
Multiple sclerosis
Musculoskeletal 336588 336588 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Each participant will receive the following:

Period 1: All 80 participants will take oral tizanidine daily according to the following schedule:
Week 1 - Oral tizanidine 2mg taken three times daily (TID) (6mg/day)
Week 2 - Oral tizanidine 4mg TID (12mg/day)
Week 3 - Oral tizanidine 6mg TID (18mg/day)

Period 2, washout and Period 3: At the commencement of Period 2, participants will be randomized to 1 of 4 fixed-sequence, crossover treatment groups. The treatment groups for periods 2 and 3 run for 7 days each. Participants will receive either oral tizanidine or the MRX-4TZT tizanidine transdermal delivery system (TDS) in each period. There will be a minimum 4-day washout between treatment period 2 and 3. All participants will receive oral tizanidine 6mg TID (18mg/day) during the washout period.

Group 1: Period 2 – MRX-4TZT 32 mg dose (80 cm2 TDS) once daily (QD)
Period 3 – Oral tizanidine 8 mg TID (24 mg/day)

Group 2: Period 2 – Oral tizanidine 8 mg TID (24 mg/day)
Period 3 – MRX-4TZT 32 mg dose (80 cm2 TDS) QD

Group 3: Period 2 – MRX-4TZT 40 mg dose (100 cm2 TDS) QD
Period 3 – Oral tizanidine 10 mg TID (30 mg/day)

Group 4: Period 2 – Oral tizanidine 10 mg TID (30 mg/day)
Period 3 – MRX-4TZT 40 mg dose (100 cm2 TDS) QD

Tapering off period: all participants will undergo a tapering off period at the end of Period 3, during which oral tizanidine will be administered at a dose of 18mg (6mg TID) for 3 days, followed by 12 mg (4 mg TID) for 3 days, and finally 6 mg (2 mg TID) for 3 days.

Participants will administer study drugs at site or at home, they will be trained on how to apply the MRX-4TZT. Participants will record at-home dosing details including details around the TDS application and removal, where applicable in a dosing diary. This will be monitored by study staff to ensure compliance. Participants will be advised to inform site staff if the TDS becomes loose or detaches during the wear period.
Intervention code [1] 332492 0
Treatment: Drugs
Description of the comparator or control
Oral tizanidine is an active comparator in this study.
Control group
Active

Outcomes
Primary outcome [1] 343423 0
To evaluate the safety of once daily administration of 2 TDS sizes of MRX-4TZT (32 mg and 40 mg) and 2 dose levels of oral tizanidine (8 mg and 10 mg TID) for 7 days in multiple sclerosis patients with established spasticity.
Timepoint [1] 343423 0
1. All AEs will be collected from the time of first study drug administration on Day 1 until the end of treatment (EOT) visit. 2. Changes from baseline assessments will be monitored at the following timepoints: - Clinical Lab Safety Tests - Day 22, 33 and 46. - ECGs - Day 22, 33 and 46. - Vital signs - Day 22-26, 33-37 and 46 - Physical Examinations - Day 22, 26, 33, 37 and 46 - Stanford Sleepiness Scale - Day 8, 15, 22, 26, 33 and 37.
Primary outcome [2] 344100 0
To evaluate the tolerability of once daily administration of 2 TDS sizes of MRX-4TZT (32 mg [80 cm2 TDS] and 40 mg [100 cm2 TDS]) and 2 dose levels of oral tizanidine (8 mg and 10 mg TID) for 7 days in multiple sclerosis patients with established spasticity.
Timepoint [2] 344100 0
All AEs will be collected from the time of first study drug administration on Day 1 until the end of treatment (EOT) visit.
Secondary outcome [1] 454393 0
To evaluate the PK profile of once daily administration of 2 TDS sizes of MRX-4TZT (32 mg and 40 mg) and 2 dose levels of oral tizanidine (8 mg and 10 mg TID) for 7 days in multiple sclerosis patients with established spasticity.
Timepoint [1] 454393 0
Blood samples will be collected for plasma PK analysis as follows in Period 2 and 3: a. In participants receiving TDS: PK blood samples will be collected pre dose on Day 1 (within 2 hours before the first TDS application), Day 4 (pre-removal of TDS applied on Day 3), and Day 5 (pre-removal of TDS applied on Day 4). PK blood samples will also be optionally collected 8 hours (±30 min) post dose on Day 5 (i.e., 8 hours post application of TDS on Day 5). b. In participants receiving oral tizanidine: PK blood samples will be collected pre dose (within 2 hours of the first dose of study drug administration of the day) on Day 1, Day 4, and Day 5. PK blood samples will also be collected 1 hour (±15 min) post dose on Day 1, and 4 (±15 min) hours after administration of the first dose of study drug of the day on Day 4.
Secondary outcome [2] 454394 0
To evaluate the dermal irritancy of 2 TDS sizes of MRX-4TZT (32 mg and 40 mg) administered once daily for 7 days in multiple sclerosis patients with established spasticity.
Timepoint [2] 454394 0
Dermal irritancy will be monitored on days 25, 26, 36 and 37 during the MRX-4TZT treatment period, as applicable.
Secondary outcome [3] 454395 0
To evaluate dermal adhesion of 2 TDS sizes of MRX-4TZT (32 mg and 40 mg) administered once daily for 7 days in multiple sclerosis patients with established spasticity.
Timepoint [3] 454395 0
Dermal adhesion will be monitored on days 25, 26, 36 and 37 during the MRX-4TZT treatment period, as applicable.

Eligibility
Key inclusion criteria
1. Male or female aged 18 to 70 years, inclusive, at screening.
2. Established diagnosis (per McDonald Criteria) of MS of any phenotype with stable disease status for >/=3 months prior to Day 1.
3. History of spasticity due to MS for >/= 6 months prior to Day 1.
4. Modified Ashworth Scale (MAS) score of >/= 2 in at least 1 muscle group at screening.
5. Expanded Disability Status Scale (EDSS) score of 4.0 to 7.5 at screening.
6. Has never been treated with baclofen or has previously been treated with baclofen but treatment ceased at least 28 days prior to Day 1 due to poor tolerability, lack of efficacy, or minimal clinical benefit, in the opinion of the investigator.
7. Negative tests for hepatitis B surface antigen, hepatitis C virus antibody, and HIV types 1 and 2 antibodies at screening.
8. Creatinine clearance, calculated by glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) Study equation, greater than 60 mL/min at Screening.
9. Skin type with Fitzpatrick scale score of I, II, or III, or have skin colorimeter scores equivalent to the allowed Fitzpatrick skin type.
10. Sufficient surface area and clear skin at the time of screening at the proposed TDS application sites, in the opinion of the investigator.
11. Agrees to avoid sunburn at the proposed TDS application sites during the conduct of the study.
12. Agrees to refrain from the use of make-up, creams, lotions, powders, or other topical products at the proposed TDS application sites during Period 2 and Period 3.
13. Understands the study procedures in the informed consent form (ICF) and is willing and able to comply with the protocol.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Acute MS exacerbation requiring treatment within 3 months prior to Day 1.
2. Any concomitant disease or disorder that has symptoms of spasticity, or may influence the participant’s level of spasticity, or results in an inability to rate the participant’s level of MS spasticity including infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement in the opinion of the investigator.
3. History of unstable psychiatric disease, or current signs or symptoms of significant medical disorders such as severe, progressive, or uncontrolled pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary, hematological, endocrine, immunologic, or neurological disease.
4. History of seizures at any time in the past, excluding childhood febrile seizures.
5. History of significant cognitive deficit, severe or untreated anxiety, or severe or untreated depression in the opinion of the investigator.
6. Any positive responses on the Columbia Suicide Severity Rating Scale (C-SSRS) at screening or Day 1 that indicates the individual may be at increased risk by participating in this study or may cause potential interference with study conduct or results, at investigator discretion.
7. History of malignancy that has not been in remission for >/=5 years, except effectively treated basal cell skin carcinoma.
8. Known or suspected substance abuse disorder, as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening in the opinion of the investigator, or positive drug or alcohol test at Screening or Day 1.
9. History of significant dermatologic disease or conditions such as atopy, psoriasis, vitiligo, or condition known to alter skin appearance or physiologic response (e.g., diabetes, porphyria).
10. Obvious difference in skin color between proposed TDS application sites or the presence of a skin condition, excessive hair, scar tissue, tattoo, open sores, raised moles, or damaged skin in or around the proposed TDS application sites (including sunburn, uneven skin tones), body piercings, or other disfigurations that would interfere with placement of the TDS, dermal irritancy assessment, drug absorption, or reactions to drug, in the opinion of the investigator.
11. Inability to swallow or tolerate oral medications.
12. Any other significant disease, disorder or significant laboratory finding which, in the opinion of the investigator, places the individual at risk as a result of their study participation, may influence the results of the study, or affect the individual’s ability to participate.
13. Planned elective surgery or other procedures requiring general anesthesia during the study.
14. For female participants of childbearing potential, use of oral or implanted hormonal contraception within 28 days prior to Day 1.
15. Use of baclofen within 7 days prior to Day 1.
16. Use of intravenous methylprednisolone within 3 months prior to Day 1.
17. Use of botulinum toxin A or B within 3 months prior to Day 1, with the exception of treatment for neurogenic bladder or cosmetic Botox.
18. Use of long-acting opioids or round the clock use of short-acting opioids for the treatment of pain within 28 days prior to Day 1.
19. Use of benzodiazepines within 7 days prior to Day 1.
20. Use of gabapentin or pregabalin that has not been stable for >/=3 months prior to Day 1.
21. Use of dantrolene within 7 days prior to Day 1.
22. Use of clonidine within 7 days prior to Day 1.
23. Use of any product containing tetrahydrocannabinol (THC) within 28 days prior to Day 1 (non-THC containing CBD oil/products are permitted).
24. Use of any other concomitant medications that may potentially interfere with the actions of the study drug or outcome variables, in the opinion of the investigator.
25. Known or suspected allergy to any of the formulation components of tizanidine HCl capsules (Zanaflex® or generic equivalent) or MRX-4TZT.
26. Current participation in any other investigational drug study or receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) before Day 1.

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)
Randomization will be performed centrally using an electronic system and each randomized participant will be assigned a unique randomization number. The randomization number encodes the participant’s dose and sequence assignment for Period 2 and Period 3.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerized randomization list will be used.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/02/2026
Actual
26/05/2026
Date of last participant enrolment
Anticipated
10/11/2026
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
80
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 29691 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 29692 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 29693 0
Southern Neurology - Kogarah
Recruitment hospital [4] 29694 0
Emeritus Research - Botany - Botany
Recruitment hospital [5] 29695 0
Emeritus Research - Camberwell
Recruitment hospital [6] 29696 0
Wollongong Private Hospital - Wollongong
Recruitment postcode(s) [1] 45018 0
5067 - Kent Town
Recruitment postcode(s) [2] 46039 0
2305 - New Lambton
Recruitment postcode(s) [3] 46040 0
2139 - Concord
Recruitment postcode(s) [4] 46041 0
2217 - Kogarah
Recruitment postcode(s) [5] 46042 0
2019 - Botany
Recruitment postcode(s) [6] 46043 0
3124 - Camberwell
Recruitment postcode(s) [7] 46044 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 320482 0
Commercial sector/Industry
Name [1] 320482 0
MEDRx Australia Pty Ltd
Country [1] 320482 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
MEDRx Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 323104 0
Commercial sector/Industry
Name [1] 323104 0
InClin Pty Ltd
Address [1] 323104 0
Country [1] 323104 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 319034 0
Bellberry Human Research Ethics Committee C
Ethics committee address [1] 319034 0
Ethics committee country [1] 319034 0
Australia
Date submitted for ethics approval [1] 319034 0
12/11/2025
Approval date [1] 319034 0
22/12/2025
Ethics approval number [1] 319034 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 146054 0
A/Prof Andrew Lee
Address 146054 0
Specialists on College, Suite 3/27 College Road, Kent Town, SA 5067 Australia
Country 146054 0
Australia
Phone 146054 0
+61 08 8132 0494
Fax 146054 0
Email 146054 0
[email protected]
Contact person for public queries
Name 146055 0
Mr Taylor Kilfoil
Address 146055 0
InClin Pty Ltd, Suite 210, 25/29 Berry Street, North Sydney, NSW, Australia, 2060.
Country 146055 0
Australia
Phone 146055 0
+61 408 880 403
Fax 146055 0
Email 146055 0
[email protected]
Contact person for scientific queries
Name 146056 0
Mr Taylor Kilfoil
Address 146056 0
InClin Pty Ltd, Suite 210, 25/29 Berry Street, North Sydney, NSW, Australia, 2060.
Country 146056 0
Australia
Phone 146056 0
+61 408 880 403
Fax 146056 0
Email 146056 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.