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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Metaxalone to determine its effects on drowsiness, reaction time, and thinking. Participants will take two different doses of Metaxalone, each a week apart, after consuming a high-fat meal. The trial aims to understand how the drug impacts alertness and the risk of falls. Ideal participants weigh at least 120 pounds and are generally healthy without significant medical issues affecting daily life. Those taking certain medications or with sleep disorders are not eligible. As a Phase 4 trial, Metaxalone has already received FDA approval and proven effective; this research seeks to understand how it benefits more patients.

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.

What is the safety track record for Metaxalone?

Research has shown that Metaxalone is usually well-tolerated. Studies have identified the most common side effects as drowsiness and dizziness, which may intensify when taken with food. Other reported side effects include headaches, nausea, and nervousness.

Metaxalone has received FDA approval as a muscle relaxant, indicating it has passed extensive safety tests for its approved use. However, participants should exercise caution, especially with activities like driving, as the drug can reduce alertness.

While Metaxalone is considered safe, participants should remain aware of these possible side effects and discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using Metaxalone for drowsiness and cognition because it offers a potentially unique approach compared to existing treatments. Unlike common medications that primarily focus on stimulating the central nervous system to combat drowsiness, Metaxalone is typically known as a muscle relaxant. This trial is exploring its effect on cognition, which could reveal benefits like improved alertness and mental clarity without the jitters or side effects associated with traditional stimulants. Additionally, the trial is testing two dosages—640 mg and 800 mg—to determine the optimal balance of effectiveness and minimal side effects, offering hope for a more personalized treatment strategy.

What evidence suggests that Metaxalone might be an effective treatment for drowsiness and cognition?

Research shows that Metaxalone works well as a muscle relaxant and is less likely to cause drowsiness compared to similar drugs. Studies find it is generally safe when taken as directed, though it can cause side effects like sleepiness, nausea, and dizziness. This trial will compare two dosages of Metaxalone, 800 mg and 640 mg, to evaluate their effects on drowsiness and cognition. While Metaxalone is known for its safety, limited evidence supports its effectiveness in addressing sleepiness or cognitive issues. However, it is used to ease pain from muscle injuries, which might improve clarity of thought by reducing pain. Overall, Metaxalone is trusted for its primary use, but more research is needed to understand its effects on sleepiness and cognition. ^{6 7 8 9 10}

Who Is on the Research Team?

J Lukban, DO

Principal Investigator

Primus Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06348303

Study to Assess Drowsiness, Cognition, Fall Risk After ... 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 ...

2. withpower.com withpower.com/trial/phase-4-sleepiness-2-2024-131a7

Metaxalone for Drowsiness and Cognition Metaxalone is generally safe for humans at prescribed doses, but higher doses can lead to more serious effects like drowsiness, nausea, and dizziness. Rarely, ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06348303/study-to-assess-drowsiness-cognition-fall-risk-after-metaxalone-640-mg-and-metaxalone-800-mg

Study to Assess Drowsiness, Cognition, Fall Risk After ... 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 ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/013217s053lbl.pdf

Skelaxin (metaxalone) tablets - accessdata.fda.gov Safety and effectiveness in children 12 years of age and below have not been established. The most frequent reactions to metaxalone include: CNS: drowsiness, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18711953/

Choosing a skeletal muscle relaxant Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and ...

6. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Metaxalone

Metaxalone | C12H15NO3 | CID 15459 - PubChem - NIH 7.10 Drug Warnings ... The most frequent adverse effects of metaxalone are drowsiness, dizziness, headache, nervousness or irritability, nausea, vomiting, and GI ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/metaxalone-oral-route/description/drg-20071948

Metaxalone (oral route) - Side effects & dosage This medicine may make you dizzy, drowsy, or less alert than you are normally. These effects may be increased if you take this medicine with food. Do not drive ...

8. webmd.com webmd.com/drugs/2/drug-7898/metaxalone-oral/details

Metaxalone (Skelaxin) - Uses, Side Effects, and More The risk of drowsiness and dizziness may be increased if you drink alcohol with it. Does metaxalone interact with other medicines (drug ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2006/013217s046lbl.pdf

SKELAXIN® (Metaxalone) Tablets ... The most frequent reactions to metaxalone include: CNS: drowsiness, dizziness, headache, and nervousness or “irritability”;. Digestive: nausea, vomiting, ...

10. drugs.com drugs.com/mtm/metaxalone.html

Metaxalone Uses, Side Effects & Warnings Taking this medicine with food may cause increased drowsiness or dizziness. This medicine can affect the results of certain medical tests. Tell ...