CLINICAL TRIALS PROFILE FOR DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE

All Clinical Trials for DEXTROMETHORPHAN HYDROBROMIDE; 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.
NCT02153502 ↗	Efficacy, Safety, and Tolerability Study of AVP-786 as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment	Completed	Avanir Pharmaceuticals	Phase 2	2014-07-01	The objectives of this 10-week study are to evaluate the efficacy, safety, and tolerability of AVP 786 as an adjunctive therapy compared with placebo in patients with major depressive disorder (MDD) who have shown an inadequate response to standard antidepressant treatment. A secondary objective of this study is to assess the pharmacokinetics (PK) of AVP-786 and potential correlations with pharmacodynamic effects.

Clinical Trial Conditions for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE

Condition Name

Condition Name for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE
Intervention	Trials
Agitation in Patients With Dementia of the Alzheimer's Type	3
Pseudobulbar Affect (PBA)	1
Schizophrenia	1
Agitation in Alzheimer's Disease	1

Condition MeSH

Condition MeSH for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE
Intervention	Trials
Psychomotor Agitation	3
Dementia	3
Alzheimer Disease	3
Depressive Disorder, Treatment-Resistant	1

Clinical Trial Locations for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE

Trials by Country

Trials by Country for DEXTROMETHORPHAN HYDROBROMIDE; 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; QUINIDINE SULFATE
Location	Trials
Florida	7
Ohio	6
New York	6
Massachusetts	6
Illinois	6

Clinical Trial Progress for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE

Clinical Trial Phase

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

Clinical Trial Status

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

Clinical Trial Sponsors for DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE

Sponsor Name

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

Sponsor Type

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

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

Last updated: July 29, 2026

Executive summary: Dextromethorphan hydrobromide plus quinidine sulfate is a combination used to deliver dextromethorphan (primarily via NMDA-pathway modulation, sigma-1 activity, and downstream neuroactive effects) at clinically relevant exposure levels. Quinidine is included as a CYP2D6 inhibitor to reduce dextromethorphan metabolism. Market outlook depends on (1) whether the product is positioned and reimbursed in neurologic or psychiatric indications with clear endpoints, (2) payer access and specialty channel adoption, and (3) competitive entrants, including deuterated or reformulated dextromethorphan products and NMDA-pathway agents. Patent and exclusivity risk will be driven by indication-specific method-of-use and formulation IP rather than the salt combination itself, with regulatory exclusivity tied to the approved indication and FDA reference listed drug history.

Scope note (what this analysis covers): This update is limited to the combination of dextromethorphan hydrobromide with quinidine sulfate, focusing on clinical development momentum, competitive and market dynamics, and forward projections at a program level rather than on a single branded SKU.

---

What clinical trials exist for dextromethorphan hydrobromide plus quinidine sulfate and what are the latest results?

Which indications are being targeted and how are endpoints measured?

Dextromethorphan plus quinidine development has historically clustered around central nervous system disorders where modulation of glutamatergic signaling and neuroprotective pathways is implicated. Clinical programs typically emphasize:

• Symptom rating scale change from baseline (primary endpoints)
• Responder rate thresholds
• Functional measures and clinician global impression
• Safety endpoints driven by tolerability and cardiac conduction risk associated with quinidine exposure (QT/QRS monitoring)

What phases matter for near-term commercialization?

For revenue projection, the gating items are:

• Phase 3 completion and readiness for BLA sNDA submission
• FDA acceptability and label-confirming endpoint strategy
• Timing of trial readouts and any confirmatory requirements post-approval

Trial readouts and design patterns

Across CNS combination programs using quinidine-boosted dextromethorphan, the same operational pattern appears in trial designs:

• Randomized placebo- or active-controlled studies
• Fixed dosing with titration steps tied to tolerability
• Stratification by baseline severity and sometimes antidepressant/antipsychotic background medication
• Longitudinal safety follow-up to manage QT risk

Actionable interpretation: If the most recent readouts show durable effect size on validated scales with stable safety profiles, payer adoption is likely to track label breadth. If effect sizes are modest or safety signals narrow the therapeutic window, commercialization becomes contingent on subpopulation positioning and sequencing with existing standard-of-care.

---

How does the dextromethorphan hydrobromide/quinidine sulfate safety profile affect dosing and labeling?

What are the key safety drivers for quinidine-boosted exposure?

Clinical dosing is constrained by quinidine’s pharmacologic effects and class-related risks:

• QT prolongation risk and cardiac monitoring requirements
• Drug-drug interactions through CYP2D6 inhibition
• Tolerability issues that can lead to discontinuation (GI effects, CNS adverse events)
• Withdrawal and rebound considerations after long-term use (trial-specific)

Do CYP2D6 interactions change real-world eligibility?

Yes. CYP2D6 inhibition alters metabolism of concomitant medications, creating exclusion or caution in:

• Patients taking other QT-active drugs
• Patients on multiple serotonergic or antidepressant agents metabolized by CYP2D6
• Patients with cardiac conduction abnormalities

Actionable interpretation: In high-volume markets, safety-driven patient selection can limit TAM penetration unless the label includes clear monitoring pathways that physicians can implement in routine practice.

---

What is the Orange Book status of dextromethorphan hydrobromide plus quinidine sulfate and what does it mean for generic risk?

How exclusivity typically works for combination CNS drugs

Orange Book risk is less about the salts and more about:

• Method-of-use patents tied to the specific clinical indication
• Formulation patents that enable exposure (including controlled-release or specific ratios)
• Process/manufacturing patents affecting impurity profiles and stability

Generic entry risks for the combination

For combination products with a boosting component:

• A generic can be blocked if it must replicate the same dosing ratio and exposure profile.
• Even if a generic is possible at bioequivalence, patent infringement can be driven by method-of-use claims.
• If the originator’s IP estate is indication-specific, generics may enter only for non-patented indications or after successful paragraph IV challenges.

Actionable interpretation: If the dominant patents are method-of-use and still active, “generic launch” timelines will move from “chemical generic availability” to “indication-specific carve-outs,” affecting forecasted price erosion.

---

Which patents protect dextromethorphan hydrobromide plus quinidine sulfate and what is the likely expiration schedule?

How to map the patent estate to revenue risk

In practice, revenue protection usually comes from three layers:

1. Composition or combination claims (less common to drive long exclusivity for salts)
2. Formulation claims affecting stability, dissolution, or pharmacokinetics
3. Method-of-use claims for each approved indication

Expiration schedule mechanics

Revenue-impacting milestones:

• Earliest non-provisional filing that controls term
• PTA (patent term adjustment) that can extend expiration
• FDA exclusivity periods (5-year new chemical entity vs 3-year new clinical investigation vs 7-year for orphan, depending on applicable facts)
• Patent term overlap between different claim families

Actionable interpretation: If multiple claim families overlap through the later years of the decade, generic timing compresses to fewer plausible entry windows, often making settlement more likely.

---

Are there paragraph IV challenges, and what patent litigation affects generic entry?

How litigation changes launch probabilities

The market impact differs by case posture:

• Filed but stayed challenges may delay generic entry with no market disruption
• Settlements can create delayed launch horizons beyond expiration
• Consent judgments or injunction outcomes can force redesign or non-infringing labeling

What to watch in filings

For a quinidine-boosted dextromethorphan product, the most litigation-relevant issues include:

• Whether generic dosing ratios and bioequivalence enable infringement of formulation claims
• Whether label instructions infringe method-of-use claims
• Whether cardiac monitoring language and patient selection create carve-outs

Actionable interpretation: Litigation that targets method-of-use claims can substantially slow generic uptake even if composition patents are weak or already expired.

---

When does dextromethorphan hydrobromide plus quinidine sulfate lose exclusivity?

Exclusivity and patent overlap

Loss of exclusivity occurs on the later of:

• Patent expiration for the relevant claim family
• Expiration of FDA exclusivity tied to the indication
• Completion of any pediatric exclusivity extensions (if applicable)

Actionable interpretation: For combination CNS agents, “effective exclusivity” often lasts longer than the earliest patent because method-of-use claims and label restrictions can delay generic substitution.

---

What is the market size for dextromethorphan hydrobromide plus quinidine sulfate and how fast is adoption?

Market sizing approach for combination CNS drugs

A credible top-down projection typically triangulates:

• Indication incidence and treated prevalence
• Uptake rate after approval tied to line-of-therapy and prescriber comfort
• Average realized price after rebates and payer contracting
• Treatment duration per year and discontinuation rates

Adoption constraints that drive underperformance risk

• Competing neurologic agents with stronger efficacy signals or more tolerable profiles
• Requirement for ECG monitoring and prescribing infrastructure
• Sensitivity to drug-drug interactions in comorbid populations
• Off-label use substitution when patients can’t meet label criteria

Actionable interpretation: In CNS markets, payer behavior matters as much as clinical efficacy. If the combination is restricted to specialty pharmacies or requires prior authorization, the adoption curve flattens even when clinical uptake is strong.

---

How does the product compare with alternatives in its therapeutic area?

Competitive set structure

Competition typically comes from:

• Other NMDA-pathway modulators
• Sigma-1 agonist strategies and glutamatergic modulators
• Antidepressants or antipsychotics used off-label to cover overlapping symptom domains
• Novel agents with improved safety or less interaction burden

What matters competitively

• Magnitude of symptom improvement vs placebo in endpoints that payers consider
• Safety profile in elderly and comorbid cardiac patients
• Drug interaction burden and monitoring requirements
• Evidence for onset speed and durability

Actionable interpretation: If the combination has a differentiated mechanism but limited safety margin, it wins in prescriber segments that can manage monitoring and interactions; it loses in broader primary care or non-specialty settings.

---

Commercial projection: revenue outlook for dextromethorphan hydrobromide plus quinidine sulfate

Base-case revenue model structure (what determines the curve)

A practical projection uses:

• Patient starts (per quarter)
• Discontinuation and persistence (median duration)
• ASP assumptions net of rebates
• Uptake sensitivity to label breadth and guideline adoption
• Generic entry probability and timing

Three scenario framework

• Bull case: robust label positioning, strong endpoint differentiation, limited safety friction, minimal substitution before end of exclusivity
• Base case: steady growth with moderate payer friction, competition constrained by monitoring needs
• Bear case: effect size and tolerability reduce tiering, competitive entrants expand, and substitution accelerates on earlier carve-outs

Actionable interpretation: Without indication-specific sales history and FDA approval dates, the only decision-useful way to project is via scenario ranges tied to exclusivity and competitive timing. The combination’s revenue will likely be most sensitive to (1) patent exclusivity duration in the core indication and (2) the earliest point when payers can operationally prefer a safer or more convenient alternative.

---

Key development and regulatory milestones to monitor next

FDA pathway signals that change investment risk

• Filing acceptance and complete response timeline
• Label scope relative to trial population
• Postmarketing requirements tied to ECG monitoring, interaction management, or risk evaluation
• Any requested restricted distribution plans

Trial conduct signals

• Enrollment pace changes indicating endpoint confidence
• Amendment disclosures that narrow populations after interim safety review
• Consistency across subgroup analyses that affect label credibility

---

Key Takeaways

• Dextromethorphan hydrobromide plus quinidine sulfate market trajectory depends on how well the clinical program differentiates efficacy on validated endpoints versus placebo and competing mechanisms.
• Quinidine-driven CYP2D6 inhibition increases interaction and monitoring complexity, which can cap broader payer adoption even with clinical benefit.
• Exclusivity and generic risk are likely dominated by indication-specific method-of-use and formulation IP rather than by the salt combination itself.
• Revenue projections should be scenario-based around exclusivity end, litigation-driven launch delays, and payer access constraints, with greatest sensitivity to post-approval label breadth and monitoring burden.
• Competitive substitution will hinge on convenience, safety practicality, and the ability to integrate into routine practice without high monitoring costs.

---

FAQs

1) What patient populations are most likely to be restricted for dextromethorphan hydrobromide plus quinidine sulfate?
Patients with QT prolongation risk factors, those with significant cardiac conduction abnormalities, and those on interacting CYP2D6 substrate or QT-active medications are typically the highest-risk groups.

2) How do CYP2D6 inhibitors and substrates affect dosing decisions in real-world use?
They can change dextromethorphan exposure and alter concomitant drug concentrations, prompting dose adjustments, avoidance, or enhanced monitoring.

3) What endpoints matter most for payers approving dextromethorphan plus quinidine?
Validated symptom scales with clinically meaningful effect size, durability, and safety metrics that demonstrate a manageable risk-benefit profile.

4) What competitive threats could erode dextromethorphan plus quinidine adoption before exclusivity ends?
New NMDA-pathway or sigma-1 strategies with superior tolerability, less interaction burden, or easier administration can shift payer preference and prescriber behavior.

5) What litigation outcomes most directly delay generic substitution of dextromethorphan plus quinidine?
Settlements and injunctions tied to method-of-use claims and label design can delay entry even if composition patents are weaker.

---

References (APA)

1. U.S. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA.
2. FDA. Drug Approval Package and labeling documents for relevant dextromethorphan/quinidine combination approvals and changes. FDA.
3. FDA. Guidance documents on REMS, postmarketing requirements, and labeling risk management strategies. FDA.