CLINICAL TRIALS PROFILE FOR CARDIZEM

All Clinical Trials for Cardizem

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00223717 ↗	Treatment of Supine Hypertension in Autonomic Failure	Completed	Vanderbilt University	Phase 1	2001-01-01	Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined. In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997). Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF. It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.
NCT00223717 ↗	Treatment of Supine Hypertension in Autonomic Failure	Completed	Vanderbilt University Medical Center	Phase 1	2001-01-01	Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined. In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997). Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF. It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.
NCT00313157 ↗	RATe Control in Atrial Fibrillation	Completed	Asker & Baerum Hospital	Phase 3	2006-04-01	The purpose of this study is to compare the effect of metoprolol, verapamil, diltiazem and carvedilol on ventricular rate, working capacity and quality of life in patients with chronic atrial fibrillation.
NCT00578617 ↗	Ablation vs Drug Therapy for Atrial Fibrillation - Pilot Trial	Completed	Abbott Medical Devices	N/A	2006-09-01	The CABANA pilot study is designed to test the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of the elimination of atrial fibrillation (AF) is superior to current state-of-the-art therapy with either rate control or anti-arrhythmic drugs for reducing AF recurrences at 1 year follow-up.
NCT00578617 ↗	Ablation vs Drug Therapy for Atrial Fibrillation - Pilot Trial	Completed	Duke Clinical Research Institute	N/A	2006-09-01	The CABANA pilot study is designed to test the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of the elimination of atrial fibrillation (AF) is superior to current state-of-the-art therapy with either rate control or anti-arrhythmic drugs for reducing AF recurrences at 1 year follow-up.

Clinical Trial Conditions for Cardizem

Condition Name

Condition Name for Cardizem
Intervention	Trials
Atrial Fibrillation	4
Healthy	1
Heart Failure	1
Hypertension	1

Condition MeSH

Condition MeSH for Cardizem
Intervention	Trials
Atrial Fibrillation	4
Hypertension	2
Atrial Flutter	1
Pure Autonomic Failure	1

Clinical Trial Locations for Cardizem

Trials by Country

Trials by Country for Cardizem
Location	Trials
United States	21
Norway	1
Canada	1

Trials by US State

Trials by US State for Cardizem
Location	Trials
Minnesota	2
Tennessee	2
Arizona	1
Utah	1
Pennsylvania	1

Clinical Trial Progress for Cardizem

Clinical Trial Phase

Clinical Trial Phase for Cardizem
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	2
Phase 1	3

Clinical Trial Status

Clinical Trial Status for Cardizem
Clinical Trial Phase	Trials
Completed	6
Unknown status	1
Withdrawn	1

Clinical Trial Sponsors for Cardizem

Sponsor Name

Sponsor Name for Cardizem
Sponsor	Trials
Mayo Clinic	2
Medtronic	1
University of Arkansas	1

Sponsor Type

Sponsor Type for Cardizem
Sponsor	Trials
Other	10
Industry	5

Cardizem (diltiazem) Clinical Trials Update, Market Analysis, and Exclusivity-to-Generic Projection

Last updated: July 28, 2026

Cardizem is the brand name for diltiazem, a calcium channel blocker with long-established, largely generic competition in the US. For “Cardizem” as labeled in FDA and marketing channels, the commercial outlook is dominated by (1) ongoing patent and exclusivity expirations tied to specific Cardizem dosage forms (immediate-release vs extended-release) and (2) the pace at which ANDA filers can launch diltiazem generics or authorized competitors as formulation and method-of-use IP expires. A complete, IP-linked projection requires Orange Book-specific mappings for the exact Cardizem NDC(s) and the specific extended-release or immediate-release product variants in scope.

What clinical trials are ongoing or recently completed for Cardizem (diltiazem) in 2024–2026?

Answer: Recent Cardizem-specific development is generally not “new pivotal therapy” at late stage; diltiazem studies are more often comparative cardiovascular studies, dosing/PK in specific populations, and device or rhythm-control adjunct research. Trial visibility is typically product-agnostic (diltiazem) rather than “Cardizem” branded. Without the exact Cardizem dosage forms and NDCs, a precise, branded-only trial list cannot be compiled without risking incorrect attribution.

Which indications keep diltiazem trial activity alive?

Common study themes across diltiazem (class) in modern registries include:

• Atrial fibrillation (rate control), atrial flutter and SVT comparisons
• Hypertension and angina subgroup comparisons
• Pharmacokinetics and food-effect studies for oral extended-release formulations
• Real-world evidence evaluations that do not require new NDA-level development

What endpoints are most frequently used?

• Heart rate reduction and time-to-rate control in AF/SVT settings
• Blood pressure change vs comparator calcium channel blockers or beta-blockers
• Safety endpoints: AV block, bradycardia, hypotension
• PK endpoints: Cmax, Tmax, AUC, bioequivalence in special populations

What is the Orange Book status of Cardizem (diltiazem) and how many patents cover it?

Answer: Cardizem’s US availability is already heavily generic. The Orange Book estate for “Cardizem” depends on the exact formulation listed (immediate-release tablets vs CD/ER capsule/tablet versions). Without the specific listed drug and NDC, a correct count of active patents and expiration dates cannot be produced.

How does patent coverage typically break down for diltiazem brands?

For long-lived cardiovascular brands, the Orange Book listing usually spans:

• Drug substance and known salt/base coverage (often expired for diltiazem)
• Formulation patents for extended-release matrices or bead/coated systems
• Bioavailability or dissolution-related formulation patents
• Method-of-use patents for specific therapeutic regimens (fewer for diltiazem than for newer oncology or specialty drugs)

What investors usually check first

• Whether the Cardizem listed drug has an unexpired period of exclusivity (rare for such an older molecule)
• Whether any formulation patents are still active and require ANDA design-around

When does Cardizem lose exclusivity and what is the generic launch risk window?

Answer: Cardizem’s branded exclusivity is largely historical. The forward-looking “generic risk window” is driven less by fixed exclusivity and more by whether any remaining listed formulation patents still block paragraph IV ANDAs for specific dosage forms.

How to map exclusivity vs patent expiry for projection

In practice, the launch timing is constrained by:

• Expiration of each Orange Book patent (not “brand exclusivity” in general)
• Any pediatric exclusivity or other statutory exclusivity extensions attached to the NDA/NDA supplements
• Litigation stays triggered by paragraph IV filings and settlements (if present)

Which companies market Cardizem and how does the competitive landscape look by dosage form?

Answer: Cardizem (diltiazem) faces broad competition from multiple generic manufacturers across oral tablets and extended-release versions. The market is characterized by:

• High substitution to AB-rated generics
• Price compression after new ANDA launches
• Limited differentiation because efficacy is class-level and formulation patents, when present, tend to be dosage-form specific

What matters commercially

• Whether a manufacturer’s ANDA is “first-to-market” for a specific strength or release mechanism
• Supply reliability of controlled-rate-release products
• Contracting and pharmacy benefit management preferences for lowest-cost AB equivalent

What patent litigation affects Cardizem (diltiazem) and how do settlements change timing?

Answer: For older cardiovascular brands, diltiazem litigation is typically sporadic, often resolved through early ANDA settlements that include payment and launch-design terms. A litigation-to-timing projection requires the patent-by-patent docket for the specific Cardizem listed drug entries; otherwise, it risks misdating launch barriers.

Common litigation effects on projections

• Automatic 30-month stay after paragraph IV certification
• Narrow design-around pathways that reduce delay to eventual launch
• Settlement-based agreed launch dates or scope-limiting terms

How strong is the patent estate for Cardizem formulations (immediate-release vs extended-release)?

Answer: The patent estate strength is generally weak for diltiazem as an active ingredient because molecule-level novelty is long exhausted. The remaining enforceable value, when it exists, tends to be formulation-specific (extended-release) rather than broad method-of-use.

Typical “estate strength” indicators used by counsel

• Number of active patents listed per dosage form
• Claim breadth over dissolution profile and release mechanism
• Whether competitors already have allowed ANDAs or have launched
• Recent Federal Circuit or district court rulings affecting validity or infringement

What formulations of diltiazem are protected for Cardizem, and what generic design-arounds are feasible?

Answer: Where formulation patents still exist, typical design-arounds focus on:

• Release mechanism changes (different coating or matrix technologies)
• Dissolution and bioequivalence profile targeting to avoid infringement
• Different excipient systems that maintain similar PK while changing claimed elements

What “design-around feasibility” depends on

• Whether claims are tied to structural features (coating layers, bead geometry, polymer types)
• Whether claims are tied to functional dissolution targets with defined ranges
• Whether the protected technology is essential vs optional

What is the FDA regulatory status for Cardizem: ANDA, 505(b)(2), and interchangeability?

Answer: Cardizem has extensive ANDA coverage. The practical regulatory path is AB substitution once an ANDA is approved for the same active ingredient, dosage form, and strength with demonstrated bioequivalence.

Key projection drivers for regulatory timing

• Whether new ANDAs require new BE studies to maintain quality and scale
• Whether FDA accepts certain formulation adjustments as within BE tolerances
• Whether interchangeability designation is applicable at state-level decision points (commercially relevant but not a core FDA exclusivity driver)

Market analysis: Cardizem (diltiazem) revenue exposure, pricing trends, and demand outlook

Answer: For diltiazem, demand is steady due to entrenched use in cardiology and hypertension/angina/rate control workflows. Revenue trajectory is typically characterized by:

• Continued generic share gains
• Brand share erosion driven by price differentials
• Periodic step-downs around major ANDA launches
• Net revenue stabilization only when brand supply and contracting keep it in formularies

What drives demand in practice

• AF management guidelines emphasizing rate control options
• Cost sensitivity and payer preference for generics
• Persistence: oral chronic use with relatively stable patient cohorts
• Safety monitoring: bradycardia and conduction disease screening

How to project Cardizem (diltiazem) market share over the next 3–5 years?

Answer: A 3–5 year projection for branded “Cardizem” should be built on three time-linked variables:

1. Remaining active Orange Book patents for each Cardizem listed drug/strength
2. Whether paragraph IV settlements create delayed generic entries
3. The pace and scale of subsequent ANDA approvals and launches

A generic-first model usually implies:

• Brand share declines in most strengths where patents are expired
• Branded revenues become more sensitive to payer contracting than to clinical differentiation
• Extent of remaining dosage-form-level formulation exclusivity determines whether there is any mid-horizon “last protected strength” effect

Key Takeaways

• Cardizem is an older, heavily genericized diltiazem brand; forward-looking market and trial impacts are mostly driven by dosage-form-specific patent and regulatory timelines rather than new clinical development.
• A precise exclusivity-to-generic projection requires Orange Book mapping for the exact Cardizem listed drug and NDCs (immediate-release vs extended-release) and the active patent set tied to those listings.
• Competitive dynamics are dominated by AB-rated generic substitution and price compression; any remaining brand value tends to be tied to narrow formulation barriers and payer contracting rather than unique mechanism-of-action differentiation.

FAQs

1. What’s the difference between Cardizem immediate-release and extended-release formulations that changes generic interchangeability?
2. Which diltiazem strengths have the highest generic price pressure in US community pharmacies?
3. How do paragraph IV ANDA stays and settlements typically affect the launch timing for older cardiovascular brands like Cardizem?
4. Are diltiazem studies in atrial fibrillation shifting toward combination regimens, and what does that mean for demand?
5. What Orange Book listing patterns (patent vs exclusivity) most often determine whether an ANDA can launch for extended-release dosage forms?

References

1. FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. (accessed 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
2. ClinicalTrials.gov. (accessed 2026). https://clinicaltrials.gov/