Metaxalone vs Tizanidine for Cognitive Impairment

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Primus Pharmaceuticals

Must not be taking: Cimetidine, Antidepressants, Antibiotics, others

Disqualifiers: Sleep-wake medications, Mind altering drugs, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that affect the sleep-wake cycle, cimetidine, certain antidepressants, and certain antibiotics. If you are using any of these, you would need to stop before participating.

How does the drug Metaxalone differ from other treatments for cognitive impairment?

Metaxalone is primarily a muscle relaxant used for muscle pain, and its use for cognitive impairment is novel, as there are no standard treatments specifically targeting cognitive impairment with this drug. This makes it unique compared to other treatments that are typically used for cognitive issues. ^{1 2 3 4 5}

What is the purpose of this trial?

Every participant will receive active study drug and one (1 )comparator, in two (2) stages, one after the other. Each drug will be taken one (1) time after a high fat meal. Vital signs and discussion of medications, illness or injury are considered safety assessments and will be discussed at every visit. There will be ( four (4) visits.

Research Team

J C Lukban, DO

Principal Investigator

Sponsor GmbH

Eligibility Criteria

This trial is for individuals who experience muscle weakness (hypotonia) and may have cognitive impairments. Participants should be able to attend four visits, take the study drug after a high-fat meal, and discuss their health status at each visit.

Inclusion Criteria

Medically healthy

Able to eat a high fat meal

I weigh at least 120 pounds.

Exclusion Criteria

Positive urine drug test for mind altering medications

I am currently taking antibiotics.

I am currently taking anti-depressants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline

Participants undergo cognitive and driving simulation tests

1 day

1 visit (in-person)

Treatment

Participants receive single doses of study drugs and undergo repeated cognitive and driving tests

2 weeks

2 visits (in-person)

Follow-up

End of study safety assessments and discharge instructions

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Metaxalone 640 mg (M640)

Trial Overview The trial is testing the effects of Metaxalone 640 mg on truck driving ability and cognition compared to Tizanidine. Each participant will try both drugs in two stages, with each drug taken once post-meal.

Participant Groups

Group I: tizanidine 8 mg Active Control 1 Intervention

tizanidine 8 mg tablet, single dose at Visit 2 or Visit 3

Group II: metaxalone m640 mg Active Control 1 Intervention

metaxalone micronized 640 mg tablet, single dose at Visit 2 or Visit 3

Metaxalone 640 mg (M640) is already approved in United States for the following indications:

Approved in United States as Metaxalone for:

• Acute, painful musculoskeletal conditions

Who Is Running the Clinical Trial?

Primus Pharmaceuticals

Lead Sponsor

Trials

22

Recruited

2,400+

Sun Valley Arthritis Center

Collaborator

Trials

1

Recruited

20+

Findings from Research

Instenon forte, a combination medication, showed mixed effects on cognitive performance related to driving in a study of 32 young adults (15 males and 9 females) over a long-term treatment period.

While males experienced improved concentration and short-term memory, and better performance in complex traffic situations, females showed enhanced focal attention and reactive behavior under stress, but impaired performance in complex traffic situations, indicating that Instenon does not consistently improve driving fitness in healthy young volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental psychological study of the effect of a hexobendine-etamivan-etofylline combination]. Klebel, VE.[2013]

In an animal model of cerebral ischemia, the 5-HT2 receptor antagonists pirenperone, cinanserin, and ritanserin were effective in reducing working memory impairment caused by temporary blood flow loss, as shown by a significant decrease in errors during a memory task.

Administering these antagonists immediately after blood flow restoration demonstrated their potential to protect cognitive function following ischemic events, suggesting that targeting 5-HT2 receptors could be a therapeutic strategy for preventing memory deficits after such incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of 5-HT2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat. Ohno, M., Yamamoto, T., Watanabe, S.[2019]

In a study of 111 adults with mild cognitive impairment (MCI), treatment with vortioxetine for 6 months led to significant improvements in cognitive function, as measured by the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST), with most participants reaching cognitively normal scores by the end of the study.

Vortioxetine also showed a favorable safety profile, with only 9.9% of participants reporting adverse events and 2.7% experiencing adverse drug reactions, suggesting it is a promising option for improving cognitive function in older adults with MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vortioxetine improves cognition in mild cognitive impairment. Tan, SN., Tan, C.[2023]

A single dose of the anabolic androgenic steroid 17α-methyltestosterone significantly impaired inhibitory avoidance learning in male periadolescent rats, indicating a negative impact on cognitive function during adolescence.

The study found no cognitive impairment in female rats or effects on anxiety, suggesting that the cognitive effects of AAS may be sex-specific and highlight potential risks of steroid use during critical developmental periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats. Ramos-Pratts, K., Rosa-González, D., Pérez-Acevedo, NL., et al.[2021]

A systematic review of 19 studies involving 4855 participants found that antidiabetic agents significantly improve cognitive function in individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) compared to placebo.

Among the antidiabetic agents studied, pioglitazone (15 to 30 mg) showed the greatest efficacy in enhancing cognition, suggesting a potential therapeutic role for this medication in treating cognitive decline associated with AD/MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis. Cao, B., Rosenblat, JD., Brietzke, E., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Experimental psychological study of the effect of a hexobendine-etamivan-etofylline combination]. [2013]

2. Ireland pubmed.ncbi.nlm.nih.gov

Blockade of 5-HT2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Vortioxetine improves cognition in mild cognitive impairment. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis. [2019]