Metaxalone for Drowsiness and Cognition

Overseen By J Sanders

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Primus Pharmaceuticals

Must not be taking: MAOIs, SSRIs, SNRIs, others

Disqualifiers: Sleep disorders, Drug use, 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

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications to join this trial. Specifically, you cannot use medications that affect sleep, certain antidepressants, muscle relaxants, or sedatives. If you're on any of these, you might need to stop them before participating.

Is metaxalone generally safe for humans?

Metaxalone is generally safe for humans at prescribed doses, but higher doses can lead to more serious effects like drowsiness, nausea, and dizziness. Rarely, it has been implicated in fatalities, especially when taken in large amounts or combined with other substances. ^{1 2 3 4 5}

How does the drug Metaxalone differ from other treatments for drowsiness and cognition?

Metaxalone is primarily a muscle relaxant, which is unique because it is not typically used for treating drowsiness and cognition issues. Unlike other treatments that might directly target cognitive function, Metaxalone's role in this context is novel and not well-documented, as it is usually prescribed for muscle pain relief. ^{1 2 4 6 7}

What is the purpose of this trial?

Every participant will receive Metaxalone in two (2) stages, one week after the other. A single dose of each Metaxalone dose will be taken one (1) time after a high fat meal which must be eaten within 30 minutes. Every participant will be given written tests to measure drowsiness, reaction time and thinking process and will also be asked to take walking tests to assess fall risk. Participation in this study will last approximately 2-4 weeks.

Research Team

J Lukban, DO

Principal Investigator

Primus Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for healthy individuals experiencing excessive daytime sleepiness. Participants will be involved in the study for about 2-4 weeks, taking Metaxalone after a high-fat meal and undergoing tests to assess drowsiness, cognition, and fall risk.

Inclusion Criteria

I am generally healthy with no major health issues affecting study outcomes.

I weigh at least 150 pounds.

Exclusion Criteria

Positive urine test for amphetamines, barbiturates, cocaine, opiates, benzodiazepines, or cannabinoids

I have severe liver or kidney problems.

I am currently taking cimetidine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Baseline assessments including vital signs, urine testing, and cognitive and physical tests

1 day

1 visit (in-person)

Treatment - Arm 1

Participants receive a single dose of Metaxalone 640 mg after a high-fat meal, followed by cognitive and physical tests

1 week

1 visit (in-person)

Treatment - Arm 2

Participants receive a single dose of Metaxalone 800 mg after a high-fat meal, followed by cognitive and physical tests

1 week

1 visit (in-person)

Follow-up

End of study safety visit to discuss side effects, recent medications, and any illness or injury

1 week

1 visit (phone)

Treatment Details

Interventions

• Metaxalone

Trial Overview The study is testing two doses of Metaxalone (640 mg and 800 mg) taken orally. Each participant will try both doses in separate stages to compare their effects on drowsiness, cognitive function, and balance.

Participant Groups

Group I: Active 800 mg Active Control 1 Intervention

Metaxalone 800 mg tablet, a single-dose at Visit 3 of 4 visits.

Group II: Active 640 mg Active Control 1 Intervention

Metaxalone (M640) 640 mg tablet, a single-dose at visit 2 of 4 visits.

Metaxalone 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+

ClinOhio Research Services, LLC

Industry Sponsor

Trials

2

Recruited

50+

Findings from Research

In a study of 142 adults who ingested metaxalone, higher doses (over 2400 mg) were linked to more serious medical outcomes, with 100% of these cases requiring management at health care facilities.

The most common adverse effects included drowsiness, tachycardia, and agitation, with 50.8% of cases resulting in 'no effect', indicating that while some ingestions can be serious, many do not lead to severe outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult metaxalone ingestions reported to Texas poison control centers, 2000-2006. Forrester, MB.[2013]

A case study indicates that metaxalone, a muscle relaxant, was the sole cause of death in a relatively young individual, highlighting its potential risks despite being rarely associated with fatalities.

Blood concentration levels of metaxalone were significantly high at the time of hospital admission (37.4 mcg/mL) and postmortem, suggesting that even at these levels, the drug's safety profile may need further evaluation, especially considering the blood-to-plasma ratio of 1.4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rare fatality attributed solely to metaxalone. Curtis, B., Jenkins, C., Wiens, AL.[2015]

In a study of 61 postmortem cases from 2002 to 2014, metaxalone was found at varying concentrations, with higher levels associated with overdose deaths; mean concentrations were 14.2 mg/L for additive deaths and 36.7 mg/L for primary deaths.

Notably, 34% of the cases had metaxalone concentrations at or below the therapeutic level of ≤4 mg/L, indicating that many decedents may not have been using the drug at harmful levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmortem Metaxalone (Skelaxin®) Data from North Carolina. Bishop-Freeman, SC., Miller, A., Hensel, EM., et al.[2015]

Alfaxalone, a synthetic neuroactive steroid, was found to activate human pregnane X receptors (h-PXR) more effectively than allopregnanolone in vitro, suggesting its potential for neuroprotection and cognitive maintenance.

In a clinical study involving 15 patients undergoing hip arthroplasty, those anesthetized with alfaxalone showed better cognitive performance and higher serum levels of mature brain-derived neurotrophic factor (m-BDNF) compared to those receiving propofol or sevoflurane, indicating that alfaxalone may support cognitive function post-anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial. Serrao, JM., Goodchild, CS.[2023]

A fatal overdose case involving metaxalone revealed high concentrations of the drug (19 mg/L in aortic blood) alongside other substances, indicating potential risks associated with its use, especially in combination with other medications.

The study highlights the limited information on metaxalone toxicity, as the pathologist attributed the cause of death primarily to hydrocodone intoxication, suggesting that while metaxalone can be present in overdose cases, its direct role in fatalities may require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metaxalone (Skelaxin)-related death. Poklis, JL., Ropero-Miller, JD., Garside, D., et al.[2019]

Switching from benzodiazepines to orexin receptor antagonists (suvorexant and lemborexant) improved cognitive dysfunction in four reported cases, suggesting a potential alternative treatment for patients experiencing cognitive decline due to benzodiazepine use.

Orexin receptor antagonists not only help with insomnia but also appear to mitigate the cognitive side effects associated with long-term benzodiazepine use, offering a promising option for those affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of switching from benzodiazepine to orexin receptor antagonists improves cognitive function in psychiatric disorders: four case reports. Hori, H.[2023]

A new high-throughput tandem mass spectroscopic method was developed to accurately measure metaxalone levels in human plasma, ensuring precise and reliable results for clinical studies.

The method demonstrated excellent stability and recovery rates, with no interference from other substances, making it suitable for evaluating metaxalone's effectiveness in pain relief across various plasma conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metaxalone estimation in biological matrix using high-throughput LC-MS/MS bioanalytical method. Goswami, D., Saha, A., Gurule, S., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Adult metaxalone ingestions reported to Texas poison control centers, 2000-2006. [2013]

2. England pubmed.ncbi.nlm.nih.gov

A rare fatality attributed solely to metaxalone. [2015]

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

Postmortem Metaxalone (Skelaxin®) Data from North Carolina. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial. [2023]

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

Metaxalone (Skelaxin)-related death. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Successful treatment of switching from benzodiazepine to orexin receptor antagonists improves cognitive function in psychiatric disorders: four case reports. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Metaxalone estimation in biological matrix using high-throughput LC-MS/MS bioanalytical method. [2013]