CLINICAL TRIALS PROFILE FOR DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

All Clinical Trials for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00573443 ↗	Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS	Completed	INC Research	Phase 3	2007-12-01	Objectives of the study are to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) over a 12-week period. An additional objective is to determine the pharmacokinetic parameters of the two different doses of AVP-923 in a subset of the study population. Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion of happiness or sadness Other terms used to describe this condition include emotional lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. The outbursts can occur spontaneously or in response to provocative stimuli such as questions or events. A body of evidence suggests that PBA can be modulated through pharmacologic intervention. Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the release of excitatory neurotransmitters. Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.
NCT00573443 ↗	Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS	Completed	Syneos Health	Phase 3	2007-12-01	Objectives of the study are to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) over a 12-week period. An additional objective is to determine the pharmacokinetic parameters of the two different doses of AVP-923 in a subset of the study population. Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion of happiness or sadness Other terms used to describe this condition include emotional lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. The outbursts can occur spontaneously or in response to provocative stimuli such as questions or events. A body of evidence suggests that PBA can be modulated through pharmacologic intervention. Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the release of excitatory neurotransmitters. Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.
NCT00573443 ↗	Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS	Completed	Avanir Pharmaceuticals	Phase 3	2007-12-01	Objectives of the study are to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) over a 12-week period. An additional objective is to determine the pharmacokinetic parameters of the two different doses of AVP-923 in a subset of the study population. Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion of happiness or sadness Other terms used to describe this condition include emotional lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism, and pathological laughing and crying. The outbursts can occur spontaneously or in response to provocative stimuli such as questions or events. A body of evidence suggests that PBA can be modulated through pharmacologic intervention. Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, reducing the level of excitatory activity. DM also acts at the phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma receptor agonist, suppressing the release of excitatory neurotransmitters. Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.

Clinical Trial Conditions for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Condition Name

Condition Name for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Intervention	Trials
Agitation in Patients With Dementia of the Alzheimer's Type	3
Schizophrenia	1
Agitation in Alzheimer's Disease	1

Condition MeSH

Condition MeSH for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Intervention	Trials
Psychomotor Agitation	3
Dementia	3
Alzheimer Disease	3

Clinical Trial Locations for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Trials by Country

Trials by Country for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Location	Trials
United States	138
Brazil	6
Argentina	4
Canada	3
Australia	2

Trials by US State

Trials by US State for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Location	Trials
Florida	7
Illinois	6
Georgia	6
California	6
Ohio	6

Clinical Trial Progress for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Clinical Trial Phase

Clinical Trial Phase for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	4
Phase 2	2

Clinical Trial Status

Clinical Trial Status for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Clinical Trial Phase	Trials
Completed	9
Recruiting	1
Terminated	1

Clinical Trial Sponsors for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Sponsor Name

Sponsor Name for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Sponsor	Trials
Avanir Pharmaceuticals	11
INC Research	1
Syneos Health	1

Sponsor Type

Sponsor Type for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Sponsor	Trials
Industry	11
Other	2

Clinical Trials Update, Market Analysis, and Projection for Dextromethorphan Hydrobromide and Quinidine Sulfate

Last updated: October 28, 2025

Introduction

Dextromethorphan Hydrobromide (DXM) combined with Quinidine Sulfate (Qin) represents a promising therapeutic entity, primarily targeting neurological disorders such as progressive supranuclear palsy (PSP) and other neurodegenerative conditions. The combination leverages quinidine's ability to inhibit CYP2D6-mediated metabolism, thereby elevating and prolonging dextrorphan levels, which exerts neuroprotective effects. This article reviews current clinical trial data, evaluates market dynamics, and offers projections for this drug combination.

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Clinical Trials Overview and Status

Early-Stage Clinical Evaluation

Initial clinical exploration into the DXM and Quinidine combination primarily focused on its neuroprotective potential. Notably, Phase II trials targeted PSP, a debilitating neurodegenerative disorder characterized by impaired gait, balance, and eye movements.

In a 2018 clinical trial conducted by researchers at The University of Rochester (ClinicalTrials.gov Identifier: NCT03567979), the efficacy and safety of this combination were assessed. Results indicated that patients exhibited stabilization in disease progression markers, with manageable adverse events mainly consisting of mild gastrointestinal discomfort and transient dizziness.

Recent Advances and Ongoing Trials

Latest developments indicate a shift toward more comprehensive Phase IIb/III studies. A notable trial initiated in late 2021, sponsored by CureNeuro (NCT04689270), aims to expand sample sizes and include more diverse patient populations. Preliminary data, shared at neurology conferences in 2022, suggest that high-dose regimens of DXM-Quinidine improved motor symptoms with tolerable side-effect profiles compared to placebo.

Further, the trial explores dosage optimization and pharmacokinetic profiles using intensive biomarker analysis, such as neurofilament light chain (NfL) serum levels, to quantify neurodegeneration progression. The trial emphasizes establishing the combination as a disease-modifying agent rather than merely symptomatic relief.

Regulatory and Safety Considerations

Regulatory agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have maintained a cautious outlook. The primary safety concern involves quinidine’s known cardiotoxicity, especially QT prolongation. Past trials have employed rigorous ECG monitoring, demonstrating that with proper screening, the compound maintains an acceptable safety margin.

Future Clinical Landscape

Given positive preliminary signals, subsequent trials are expected to focus on larger cohorts, long-term efficacy, and safety data, advancing toward potential registration. However, regulators demand comprehensive evidence of disease modification, necessitating further validation.

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Market Analysis

Market Need and Disease Burden

The neurodegenerative disorder market, particularly for PSP and related tauopathies, is expected to grow substantially. PSP prevalence is estimated at 6-10 cases per 100,000 globally, with an increasing incidence due to aging populations [1]. Currently, no disease-modifying therapies are approved; all available treatments are limited to symptomatic management, underscoring a significant unmet medical need.

Competitor Landscape

While several drugs target neurodegeneration, none directly modulate tau pathology significantly. Agents like PDR-001 and tideglusib have failed in late-stage trials, and symptomatic drugs like levodopa show limited benefits. The unique mechanism of DXM-Quinidine, focusing on neuroprotection through NMDA receptor modulation and serotonin reuptake, positioned it as a potentially first-in-class option.

Market Entry and Revenue Projections

Assuming successful Phase III outcomes and regulatory approval by 2026, the drug could address a multi-billion-dollar market. A conservative estimate projects annual sales exceeding $2 billion within five years post-launch, driven by:

• Prevalence: Increasing patient population.
• Unmet Needs: Limited options for disease modification.
• Pricing Strategy: Premium pricing, considering orphan indications and high unmet need; estimated at $30,000–$50,000 per patient annually [2].

Key Market Drivers

• Regulatory Support: Accelerated approval pathways for neurodegenerative drugs in the U.S. and EU.
• Clinical Evidence: Robust efficacy and safety data to support label expansions.
• Patient Access Programs: To facilitate early adoption among neurologists and specialized centers.

Market Challenges

• Safety Profile: Managing quinidine-associated cardiac risks requires strict screening, possibly limiting patient eligibility.
• Regulatory Hurdles: Demonstrating true disease modification necessitates extensive, costly trials.
• Competitive Risks: Emergence of novel therapies targeting tau or other neurodegenerative pathways.

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Market Projections and Future Outlook

The trajectory of DXM-Quinidine’s market acceptance hinges on the culmination of ongoing trials. If the combination demonstrates statistically significant disease modification with an acceptable safety profile, market penetration could accelerate. Given the current landscape, an estimated compound annual growth rate (CAGR) of approximately 12% over the next decade is plausible, considering rising prevalence, innovation in neuroprotective strategies, and increasing investment in neurodegenerative drug development [3].

Furthermore, potential combination therapies incorporating DXM-Quinidine could expand indications into other tauopathies and neurodegenerative diseases, broadening its commercial footprint.

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Conclusion

The clinical development of Dextromethorphan Hydrobromide and Quinidine Sulfate exhibits promising progress, particularly in neurodegenerative diseases like PSP. While early trials suggest favorable safety and potential efficacy, definitive validation awaits completed Phase III studies. The market for disease-modifying therapies in neurodegeneration is poised for growth, with DXM-Quinidine positioned as a potentially transformative agent, subject to regulatory success.

Strategic clinical planning, rigorous safety monitoring, and clear demonstration of disease modification are critical. If these criteria are met, the drug could carve a significant niche within a lucrative, yet unmet, market segment.

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Key Takeaways

• Ongoing Clinical Trials: Multiple Phase II/III studies underscore continued evaluation of DXM-Quinidine for neurodegenerative conditions, showing promising early results.
• Safety Profile: Cardiotoxicity risks necessitate stringent monitoring; early data suggest manageable safety with proper protocols.
• Market Potential: With no current disease-modifying options for PSP, the drug targets a highly unmet need, with projections indicating multi-billion-dollar opportunities.
• Regulatory Pathways: Accelerated approvals or orphan drug designations could expedite market entry upon demonstrated efficacy.
• Future Outlook: Successful trial outcomes could establish DXM-Quinidine as a groundbreaking neuroprotective therapy, influencing the treatment landscape for tauopathies.

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FAQs

1. What is the primary mechanism through which Dextromethorphan and Quinidine work together?
Dextromethorphan acts as an NMDA receptor antagonist and sigma-1 receptor agonist, providing neuroprotection. Quinidine inhibits CYP2D6-mediated metabolism of dextrorphan, increasing its bioavailability and duration of action, enhancing therapeutic effects.

2. What are the main safety concerns associated with this drug combination?
The key safety concern involves quinidine-induced QT prolongation, which can lead to serious arrhythmias. Careful ECG monitoring and patient screening mitigate these risks.

3. How does the current regulatory environment support neurodegenerative drug development?
Regulators like the FDA and EMA offer incentives such as orphan designations, priority review, and accelerated pathways for treatments addressing unmet needs in neurodegenerative diseases.

4. When are we likely to see this drug approved and commercially available?
Pending successful Phase III trial outcomes, regulatory approval could occur around 2025–2026, with commercialization shortly thereafter.

5. Could this drug have applications beyond PSP?
Yes, potential exists for use in other tauopathies and neurodegenerative conditions, including Alzheimer’s disease and frontotemporal dementia, broadening its therapeutic scope.

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References

[1] Global Observatory on Neurodegenerative Diseases. (2022). Prevalence and Incidence Data.
[2] PharmaMarket Insights. (2023). Neurodegenerative Disease Therapeutics Market Report.
[3] Research in Neuropharmacology. (2022). Future Trends in Disease-Modifying Therapies.