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
Pseudobulbar Affect (Involuntary Laughing and/or Crying)	1
Pseudobulbar Affect (PBA)	1

Condition MeSH

Condition MeSH for DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Intervention	Trials
Dementia	3
Alzheimer Disease	3
Psychomotor Agitation	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
Ohio	6
New York	6
Massachusetts	6
Illinois	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

Last updated: April 27, 2026

DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE: Clinical, Market and Projection Brief

What is the current clinical and regulatory status for dextromethorphan + quinidine?

Dextromethorphan hydrobromide and quinidine sulfate is marketed in the US as NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate) for pseudobulbar affect (PBA), which is now treated under broader “amyotrophic lateral sclerosis and other neurodegenerative indications” in clinical practice. The core development path for the combination predates today’s modern global trial landscape and centers on PBA symptom control.

For a clinical-trials “update” on this specific combination, the most material and decision-relevant public record remains label-linked efficacy trials for PBA rather than a high volume of new late-stage programs that materially change the competitive or pricing outlook. As a result, the market view depends more on label lifecycle, substitution risk, payer behavior, and adherence than on a steady stream of new Phase 3 readouts for the same fixed-dose combination.

Trial relevance to current commercial use

Public evidence base for NUEDEXTA’s label is dominated by:

• Randomized, controlled efficacy in PBA endpoints (frequency and severity of crying and laughing episodes)
• Long-term tolerability monitoring in open-label or extension formats
• Dose-optimization constraints tied to the pharmacokinetic role of quinidine (CYP2D6 inhibition effect on dextromethorphan exposure)

(Clinical trial specifics by NCT number and phase are label-derived and historically concentrated; no new late-stage pivot trials are required to interpret present market dynamics because the combination is already positioned for chronic use in PBA.)

How does the IP and lifecycle picture shape near-term investment value?

For fixed-dose dextromethorphan/quinidine, the business impact comes from:

• US brand exclusivity and subsequent generic entry risk
• Formulation and manufacturing process defensibility
• Patent thickets around the combination (composition of matter, method-of-use, and specific dosing regimens)

Commercially, the combination’s value proposition is “ongoing chronic use with payer reimbursement,” so the practical risk is whether substitutable generics pressure net price faster than the brand can offset through contracts.

What is the market opportunity and where does demand come from?

Demand for dextromethorphan/quinidine is driven by:

• Diagnosis prevalence and coding patterns for PBA in MS, ALS, and other neurodegenerative diseases
• Clinician adoption for long-term symptom control
• Payer coverage thresholds and prior authorization practices
• Patient adherence for chronic dosing (impact of dosing frequency and side-effect tolerability)

In practice, market sizing is typically built using:

• Treated population estimates for PBA across neurologic indications
• Treatment penetration into diagnosed patients
• Annualized utilization per patient (dose and discontinuation rate)
• Net price after rebates and pharmacy benefit manager contracting

Given the fixed-dose combination’s long-established role, growth tends to be driven by:

• Access gains (preferred formulary status, lower authorization friction)
• Switching from under-treatment (patients identified later or not treated previously)
• Stable net pricing versus competitive erosion from generics

How does competition affect pricing and share?

Competitive pressure for NUEDEXTA is typically structured around:

• Generic substitution after relevant protections expire
• Alternative PBA treatments (therapies used off-label or other approved options depending on jurisdiction and guideline alignment)
• Health plan preference and contract leverage

Key point for projection: once a generic enters, net pricing usually declines quickly, and share stabilizes based on formulary placement rather than on differentiation.

What is the most realistic market projection for the next 3 to 5 years?

Because NUEDEXTA is an established chronic therapy with predictable payer behavior, projections typically map to three drivers:

1. Generic penetration and time-to-substitution
2. Patient identification and diagnosis growth
3. Net price trajectory from contract renegotiations

A decision-grade projection needs actual sales history and actual competitor/generic timing. Without that dataset in this source-limited environment, the only accurate projection framework available is a scenario structure tied to observable market mechanisms:

• Base case: slower-than-expected price erosion if formulary management delays switching; modest volume growth from diagnosis and access.
• Downside: faster generic substitution or payer tightening; net price falls faster than volume growth can offset.
• Upside: sustained brand differentiation via contracting plus higher penetration; net price stabilizes due to preferred positioning.

To convert this into investment terms: if your plan depends on new revenue growth from new Phase 3 efficacy, the combination is not positioned that way. If it depends on defending net price and maintaining covered access, the combination remains a cash-flow style asset with lifecycle risk.

What clinical and commercial risks will matter most to outcomes?

For dextromethorphan/quinidine, the risk stack for both patients and commercial performance is dominated by:

• Tolerability and discontinuation: quinidine-related tolerability constraints can limit long-term persistence in some cohorts
• Cardiac safety screening requirements: clinical practice may require ECG and careful medication reconciliation, affecting access and continuity
• Drug-drug interactions: quinidine’s pharmacologic activity creates interaction burden that can shift prescribing decisions
• Reimbursement friction: prior authorization and step-therapy policies can depress net utilization even if efficacy is established

Where are the “watch items” for the next reporting cycles?

Near-term market movement is typically observable through:

• Pharmacy claims trends for NUEDEXTA and any generic AB-rated equivalents
• Formulary changes in large PBMs
• Label expansions or safety communications that alter prescribing constraints (if any)
• New publication cycles on PBA management that change guideline adoption and patient identification rates

Because the drug combination’s clinical role is stable, the watch items are primarily market access and substitution, not new clinical efficacy.

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Market Snapshot and Projection Framework (Actionable)

Below is the decision structure used by investors and BD teams to translate market mechanics into 3 to 5 year outcomes for dextromethorphan/quinidine.

Key variables

Variable	What moves it	What to monitor
Net price	Generic substitution, PBM contracting	Average selling price trend; formulary tiering
Volume	Diagnosed PBA prevalence, prescribing adoption	Claims volume, patient persistence
Adherence	Tolerability and interaction burden	Discontinuation signals; dose persistence
Access	Prior auth, step edits, coverage criteria	PA approval rates, coverage edits
Competitive share	Generic entrant timing and substitution speed	AB-rated share shifts post-launch

Projection logic (how to translate into numbers)

Use a simple revenue roll-forward:

• Revenue(t) = Patients treated(t) × Annualized dose utilization × Net price(t)
• Patients treated(t) grows with diagnosis and penetration, while net price(t) declines with substitution unless contracting offsets the drop.

A base-case approach assumes:

• Volume: modest growth from access and identification
• Net price: downward slope tied to generic penetration
• Margin protection: limited, unless formulary positioning remains preferred

Upside and downside scenarios are driven almost entirely by net price trajectory and switching speed.

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Key Takeaways

• Dextromethorphan hydrobromide and quinidine sulfate is an established chronic PBA therapy; near-term commercial performance is driven more by payer access and substitution risk than by new late-stage clinical readouts.
• The biggest market swing factors are generic penetration speed, formulary tiering, and net price erosion, with volume growth typically slower and steadier.
• The clinical risk profile affects persistence: tolerability, drug-drug interactions, and monitoring requirements can reduce adherence and real-world persistence.
• For projections over 3 to 5 years, model revenue via treated patients × net price, with net price as the primary uncertainty.

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FAQs

1) What condition does the combination treat?
It treats pseudobulbar affect (PBA), a neurological condition characterized by involuntary laughing and crying episodes.

2) What is the commercial product name in the US?
The combination is sold as NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate).

3) What is the main driver of market share changes?
The dominant driver is generic substitution and formulary contracting rather than new clinical trial efficacy differentiation.

4) What clinical factors most affect persistence?
Tolerability, drug-drug interactions, and monitoring requirements can influence discontinuation and prescribing continuity.

5) How should revenue be forecasted?
Use a roll-forward model with treated patient count (volume) and net price (contracting and substitution) as separate drivers.

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References

[1] FDA. NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate) prescribing information. U.S. Food and Drug Administration.
[2] FDA. NUEDEXTA drug approval and label history (product labeling and regulatory actions). U.S. Food and Drug Administration.
[3] ClinicalTrials.gov. NUEDEXTA and dextromethorphan/quinidine clinical studies (trial registry records). National Institutes of Health.