CLINICAL TRIALS PROFILE FOR TADALAFIL

505(b)(2) Clinical Trials for tadalafil

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Covance Harrogate	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Hammersmith Medicines Research	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	GlaxoSmithKline	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.

All Clinical Trials for tadalafil

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00050609 ↗	Study of Tadalafil for the Treatment of Diabetic Patients With Symptoms of Upset Stomach and Delayed Stomach Emptying	Completed	ICOS Corporation	Phase 2	2003-02-01	The purposes of this study are to determine whether an experimental drug known as tadalafil can reduce symptoms of dyspepsia (fullness after eating, inability to finish a regular meal, bloating, discomfort or pain in the upper abdomen, belching after meals, nausea, vomiting) in diabetic patients, and/or reduce the amount of time the stomach takes to empty the contents of a standard meal. The safety of tadalafil given once daily for 8 weeks in this population will also be studied.
NCT00050609 ↗	Study of Tadalafil for the Treatment of Diabetic Patients With Symptoms of Upset Stomach and Delayed Stomach Emptying	Completed	Eli Lilly and Company	Phase 2	2003-02-01	The purposes of this study are to determine whether an experimental drug known as tadalafil can reduce symptoms of dyspepsia (fullness after eating, inability to finish a regular meal, bloating, discomfort or pain in the upper abdomen, belching after meals, nausea, vomiting) in diabetic patients, and/or reduce the amount of time the stomach takes to empty the contents of a standard meal. The safety of tadalafil given once daily for 8 weeks in this population will also be studied.
NCT00122499 ↗	A Study to Assess the Efficacy of Tadalafil to Treat Erectile Dysfunction After Radiotherapy of Prostate Cancer	Completed	Erasmus Medical Center	Phase 3	2003-02-01	This study has been designed to evaluate the efficacy and safety of a 20-mg dose of tadalafil administered "on demand" to patients with erectile dysfunction (ED) after external-beam radiotherapy (EBRT) of prostate cancer.
NCT00125918 ↗	PHIRST-1: Tadalafil in the Treatment of Pulmonary Arterial Hypertension	Completed	ICOS Corporation	Phase 3	2005-08-01	The purpose of this study is to evaluate the safety and effectiveness of tadalafil for the treatment of pulmonary arterial hypertension.
NCT00125918 ↗	PHIRST-1: Tadalafil in the Treatment of Pulmonary Arterial Hypertension	Completed	Eli Lilly and Company	Phase 3	2005-08-01	The purpose of this study is to evaluate the safety and effectiveness of tadalafil for the treatment of pulmonary arterial hypertension.
NCT00157326 ↗	Tadalafil in Subjects With Mild to Moderate Hypertension	Completed	ICOS Corporation	Phase 2	2005-09-01	Purpose: The primary objective of this study is to evaluate the efficacy and safety of tadalafil when administered once daily at doses of 5 and 20 mg to adult subjects for 8 weeks with mild to moderate hypertension.

Clinical Trial Conditions for tadalafil

Condition Name

Condition Name for tadalafil
Intervention	Trials
Erectile Dysfunction	54
Benign Prostatic Hyperplasia	19
Pulmonary Arterial Hypertension	14
Impotence	11

Condition MeSH

Condition MeSH for tadalafil
Intervention	Trials
Erectile Dysfunction	71
Hypertension	35
Prostatic Hyperplasia	28
Hyperplasia	27

Clinical Trial Locations for tadalafil

Trials by Country

Trials by Country for tadalafil
Location	Trials
United States	508
Canada	63
Germany	54
Italy	37
United Kingdom	32

Trials by US State

Trials by US State for tadalafil
Location	Trials
California	33
Florida	28
Texas	23
Ohio	20
New York	20

Clinical Trial Progress for tadalafil

Clinical Trial Phase

Clinical Trial Phase for tadalafil
Clinical Trial Phase	Trials
PHASE4	2
PHASE3	7
PHASE2	6

Clinical Trial Status

Clinical Trial Status for tadalafil
Clinical Trial Phase	Trials
Completed	140
Recruiting	26
Not yet recruiting	25

Clinical Trial Sponsors for tadalafil

Sponsor Name

Sponsor Name for tadalafil
Sponsor	Trials
Eli Lilly and Company	59
ICOS Corporation	22
Actelion	6

Sponsor Type

Sponsor Type for tadalafil
Sponsor	Trials
Other	200
Industry	149
NIH	18

Tadalafil Clinical Trials Update, Market Analysis, and Expiry-Driven Generic/Biosimilar Outlook

Last updated: July 27, 2026

Tadalafil (PDE5 inhibitor; brands include Cialis and generics) is an established, off-patent small molecule in most major markets. Near-term growth is driven by penetration of once-daily regimens, formulation upgrades (where patented), and expanding label breadth in selected jurisdictions. Commercial risk is primarily tied to generic intensity and loss of any remaining exclusivity by geography and dosage form, not to biosimilar pathways.

What is tadalafil’s current clinical trials landscape and who is running key studies?

Tadalafil’s clinical pipeline in 2024-2026 is dominated by incremental studies rather than first-in-class development: new patient subgroups, dose optimization, combination regimens, real-world evidence, and product performance (bioequivalence and formulation comparisons where tied to regulatory strategy).

Which trial types are most common for tadalafil

• Phase 3: label expansion or comparative efficacy studies in specific indications (often erectile dysfunction subtypes, pulmonary hypertension variants, or lower urinary tract symptoms when studied in combination).
• Phase 4/Observational: real-world effectiveness, persistence on once-daily dosing, safety in comorbid populations (cardiovascular disease, diabetes, older adults).
• Pharmacokinetic/pharmacodynamic and formulation studies: bioequivalence, food-effect, and steadystate exposure for tablets and combinations.

Key sponsors and geographies

• Established generics and branded manufacturers run post-marketing comparative and pharmacology studies tied to their local product dossiers.
• Academic groups and national consortia conduct smaller clinical investigations, typically in urology and cardiovascular comorbidity cohorts.
• Trial activity is concentrated in Europe, North America, and major Asia-Pacific markets, with many studies registering as interventional “comparative efficacy” or “product performance.”

How to interpret the clinical update

For an off-patent molecule, trial value is usually tied to:

• supporting label positioning (claims that affect payer and prescribing patterns),
• maintaining differentiated product performance for specific dosages (Tmax/food effect where relevant),
• creating evidence for combination therapies that can preserve market share even after price erosion.

What are tadalafil’s approved indications by region, and which ones drive volume?

Tadalafil’s dominant revenue categories historically are:

• Erectile dysfunction (ED): on-demand and once-daily.
• Benign prostatic hyperplasia (BPH) and ED (some jurisdictions: combination indications or separate label lines).
• Pulmonary arterial hypertension (PAH): in many markets, tadalafil is an option in vasodilator strategies, though practice patterns depend on local guidelines and alternative therapies.

Does tadalafil have meaningful ongoing utilization growth in ED/BPH

• ED: once-daily regimens increase treatment continuity and reduce demand variability compared with on-demand dosing.
• BPH/LUTS: growth depends on competition from alpha blockers and 5-alpha reductase inhibitors, plus device and procedural options. Tadalafil’s uptake depends on whether local formularies prefer PDE5 inhibitors for LUTS subpopulations.

PAH utilization is more guideline-dependent

• PAH growth is not purely price-driven. Outcomes, combination strategies, and patient selection matter.
• Market share changes often track guideline updates and payer criteria rather than new pivotal trials.

What is the tadalafil market size and how does it evolve in 2025-2030?

Tadalafil is a mature, commodity-like product in many markets, with pricing compressed by multiple generic entries. Market value still grows modestly through:

• increased prescriptions and adherence to once-daily dosing,
• demographic drivers (aging populations),
• continued uptake in LUTS/ED dual-pathways,
• brand-to-generic migration stabilizing as competition normalizes.

Market projection (directional, driven by penetration not exclusivity)

• 2025-2026: market growth is limited and real demand growth is moderated by deep generic penetration and frequent price resets.
• 2027-2030: volume growth can continue, but value growth depends on country-specific pricing, reimbursement, and relative generic discount intensity.

Primary value drivers

• Once-daily dosing adoption (higher persistence, easier scheduling).
• Persistent provider familiarity and patient demand for PDE5 inhibitors.
• Formulation differentiation (where legally protected in a given jurisdiction).

Primary headwinds

• Continuous generic competition and manufacturing capacity expansion.
• Payer controls that impose maximum allowable prices.
• Margin compression on tablets, especially for common strengths.

Which tadalafil products and strengths capture the most share?

Global utilization concentrates on:

• 5 mg once daily (ED with or without BPH/LUTS positioning depending on region)
• 10 mg and 20 mg on-demand dosing for ED

Why 5 mg once-daily is structurally important

• It converts ED from episodic to baseline therapy.
• It is easier for patients to adhere to, improving persistence versus PRN-only patterns.

How strong is tadalafil’s patent estate and when does exclusivity expire by key geography?

For tadalafil, the practical patent question is not “does exclusivity exist,” but “does any meaningful incremental exclusivity remain” for specific formulations or combinations in particular countries.

General reality for tadalafil

• The original active ingredient is long past primary composition and basic use protections.
• Remaining IP tends to be limited to:
  • specific formulation technologies (rarely dominant at scale),
  • method-of-use claims tied to particular dosing strategies or patient subgroups (jurisdiction-dependent),
  • combination products (if any are separately protected),
  • secondary patents that may have expired or are weak once courts and generic entry pressure apply.

Exclusivity timing framework

Because tadalafil is largely off-patent, market entry dynamics are driven by:

• last remaining secondary patent expiries for differentiated products in a country,
• regulatory and patent litigation history that affects launch timing,
• settlement terms that delay generic entry in specific labels/dosages.

What Orange Book status exists for tadalafil in the US, and what does it imply for generic launch risk?

Tadalafil is listed on the US FDA Orange Book for multiple NDA/ANDA products across strengths and dosage forms. With the active ingredient long off primary exclusivity, the Orange Book record typically reflects:

• numerous ANDA approvals,
• legacy patents (often older) that may still appear for specific products,
• method-of-use or formulation patents that can affect paragraph IV strategy for certain applicants.

Practical implication

For most market participants, US generic risk is not “whether” generics exist, but:

• whether any specific ANDA-holder is delayed for a given strength based on litigation or settlement.

Which companies manufacture and compete in tadalafil’s branded and generic markets?

Branded

• Cialis (tadalafil) remains a recognizable brand in some markets where residual differentiation persists.

Generics

• Multiple global generic manufacturers supply tadalafil tablets at scale.
• Competitive intensity is highest in:
  • ED-first-line formulations,
  • 5 mg daily and common on-demand strengths where volume is greatest.

What patent litigation has affected tadalafil generic entry, and what settlement patterns matter?

Tadalafil’s litigation history includes:

• patent infringement disputes around Orange Book-listed patents,
• paragraph IV challenges tied to formulation or method-of-use listings,
• settlements that can delay specific ANDA launches for a period in the US.

How litigation impacts market outcomes

Even when patents are weak, litigation can:

• delay initial generic entry for targeted strengths,
• enable brand to defend share while price erosion accelerates later,
• shift launch timing to later windows once injunction risk declines.

What generic entry risks exist for tadalafil, and how do they vary by strength and jurisdiction?

Because tadalafil is widely generic, risk is concentrated in niche cases:

• a specific jurisdiction where a particular formulation still has enforceable IP,
• a strength/dosage packaged under a separately protected product line,
• recent product launches with unique excipients or release profiles.

Bottom line risk profile

• In most major markets, “generic entry risk” is low in the sense that generics are already entrenched.
• The economic risk is mainly margin dilution and wholesale price resets, not FDA approval blockages.

How does tadalafil compare with sildenafil and vardenafil in market positioning and trial activity?

Market positioning

• Sildenafil often competes strongly on on-demand ED.
• Tadalafil’s differentiation is usually once-daily convenience and longer pharmacodynamic profile.
• Vardenafil competes but typically faces lower brand stickiness.

Clinical evidence pattern

• Trials for tadalafil versus comparators tend to focus on patient preference, adherence, and persistence, not only mean efficacy endpoints.

What manufacturing and regulatory constraints could affect tadalafil supply or pricing?

Tadalafil is a mature small molecule, so bottlenecks are usually operational:

• API supply and impurity control for high-volume generic batches,
• compliance standards (GMP) and site inspections that can force temporary production shifts,
• regional regulatory submissions and bioequivalence requirements.

Key Takeaways

• Tadalafil is in a mature commercialization phase where clinical activity is mostly incremental and label-positioning oriented, not first-wave innovation.
• Market growth is modest and driven by uptake of once-daily regimens and demographic demand rather than new exclusivity.
• Patent-driven entry delays are geographically and formulation-specific; the base molecule is broadly off primary protection in major markets.
• Competitive pressure from entrenched generics makes pricing and margin stability the main commercial variable through 2030.
• Litigation and settlement histories matter mainly for short-term launch timing for specific strengths or product lines, not for sustained exclusivity.

FAQs

1. What once-daily tadalafil dosing strategies are most associated with improved persistence versus PRN dosing?
2. Do tadalafil LUTS/ED claims increase reimbursement coverage compared with ED-only indications in key EU markets?
3. Which tadalafil strengths face the most aggressive generic price competition in the US?
4. How do FDA bioequivalence and patent listing differences affect paragraph IV strategy for tadalafil ANDAs?
5. What combination therapies with tadalafil have the strongest clinical and payer adoption prospects?

References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. US FDA.
2. ClinicalTrials.gov. Tadalafil (interventional and observational studies). US NIH.
3. EMA. European public assessment reports and SmPCs for tadalafil-containing products. European Medicines Agency.
4. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD classification and utilization context for PDE5 inhibitors.
5. Company investor presentations and annual reports covering PDE5 inhibitor market share and generic competition (where applicable).