CLINICAL TRIALS PROFILE FOR PSEUDO-12

505(b)(2) Clinical Trials for Pseudo-12

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	NCT02973880 ↗	Clinical Study to Evaluate the Efficacy and Tolerability of an Anti-inflammatory/Antibiotic Treatment Following Ocular Cataract Extraction	Completed	Sintesi Research Srl	Phase 3	2017-10-15	Cataract is an ophthalmic disease that usually affects the elderly population. Cataract surgery with phaco-emulsification is now the most frequently performed intraocular surgical procedure in the developed world. However, differences in surgical technique impact the severity of surgical trauma and post-operative recovery. The amount of post-operative ocular pain and inflammation plays a significant role in the Patient's perception of the surgical success. Several ophthalmic products have been studied in the management of post-surgery ocular inflammation and pain following cataract surgery. Corticosteroids are considered the gold standard for the treatment of ocular inflammation, and their most commonly used route of administration is the topical instillation as eye drops formulation. After topical administration of Dexamethasone, the concentration in the anterior chamber increases and declines within hours, necessitating frequent daily instillations of eye drops for several weeks. This might be associated with compliance issues, particularly in elderly Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a less frequent administration could therefore be an attractive alternative. NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new ophthalmic gel, preservative-free formulation has been developed. This new formulation has been tested in pre-clinical animal studies and in a clinical trial. The new formulation contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for food products. It is used in the product as viscosity enhancer and to give to the product pseudo-plastic characteristics and prolonged ocular retention time. The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™ gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.
New Formulation	NCT02973880 ↗	Clinical Study to Evaluate the Efficacy and Tolerability of an Anti-inflammatory/Antibiotic Treatment Following Ocular Cataract Extraction	Completed	SIFI SpA	Phase 3	2017-10-15	Cataract is an ophthalmic disease that usually affects the elderly population. Cataract surgery with phaco-emulsification is now the most frequently performed intraocular surgical procedure in the developed world. However, differences in surgical technique impact the severity of surgical trauma and post-operative recovery. The amount of post-operative ocular pain and inflammation plays a significant role in the Patient's perception of the surgical success. Several ophthalmic products have been studied in the management of post-surgery ocular inflammation and pain following cataract surgery. Corticosteroids are considered the gold standard for the treatment of ocular inflammation, and their most commonly used route of administration is the topical instillation as eye drops formulation. After topical administration of Dexamethasone, the concentration in the anterior chamber increases and declines within hours, necessitating frequent daily instillations of eye drops for several weeks. This might be associated with compliance issues, particularly in elderly Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a less frequent administration could therefore be an attractive alternative. NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new ophthalmic gel, preservative-free formulation has been developed. This new formulation has been tested in pre-clinical animal studies and in a clinical trial. The new formulation contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for food products. It is used in the product as viscosity enhancer and to give to the product pseudo-plastic characteristics and prolonged ocular retention time. The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™ gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.

All Clinical Trials for Pseudo-12

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00148590 ↗	Memantine for the Prevention of Cognitive Dysfunction and Negative Symptoms in Patients With Acute Schizophrenia	Terminated	Stanley Medical Research Institute	Phase 3	2005-11-01	The purpose of this study is to evaluate the efficacy and safety of a 6 weeks memantine add-on to risperidon treatment for the prevention of cognitive dysfunction and negative symptomatology in patients with acute schizophrenia. Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function were measured at baseline and week 6, and 24 by the California Verbal Learning Test, Benton Learning Test, Digit Span Forward and Backward Test, Continuous Performance Test, Stroop Test, Trail-Making Test, Verbal Fluency Test, and Wisconsin Card Sorting Test.
NCT00148590 ↗	Memantine for the Prevention of Cognitive Dysfunction and Negative Symptoms in Patients With Acute Schizophrenia	Terminated	M. Schaefer, MD	Phase 3	2005-11-01	The purpose of this study is to evaluate the efficacy and safety of a 6 weeks memantine add-on to risperidon treatment for the prevention of cognitive dysfunction and negative symptomatology in patients with acute schizophrenia. Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function were measured at baseline and week 6, and 24 by the California Verbal Learning Test, Benton Learning Test, Digit Span Forward and Backward Test, Continuous Performance Test, Stroop Test, Trail-Making Test, Verbal Fluency Test, and Wisconsin Card Sorting Test.
NCT00148616 ↗	Memantine for the Treatment of Cognitive Dysfunction and Negative Symptoms in Patients With Chronic Schizophrenia	Terminated	Stanley Medical Research Institute	Phase 3	2004-04-01	The purpose of this study is to evaluate the efficacy and safety of 24 weeks memantine add-on treatment to risperidone for the treatment of negative symptomatology and cognitive impairment in patients with chronic schizophrenia.
NCT00148616 ↗	Memantine for the Treatment of Cognitive Dysfunction and Negative Symptoms in Patients With Chronic Schizophrenia	Terminated	M. Schaefer, MD	Phase 3	2004-04-01	The purpose of this study is to evaluate the efficacy and safety of 24 weeks memantine add-on treatment to risperidone for the treatment of negative symptomatology and cognitive impairment in patients with chronic schizophrenia.

Clinical Trial Conditions for Pseudo-12

Condition Name

Condition Name for Pseudo-12
Intervention	Trials
Schizophrenia	5
Glioma	4
Glioblastoma	3
Chronic Intestinal Pseudo-obstruction	3

Condition MeSH

Condition MeSH for Pseudo-12
Intervention	Trials
Glioblastoma	6
Hemorrhage	6
Glioma	6
Schizophrenia	6

Clinical Trial Locations for Pseudo-12

Trials by Country

Trials by Country for Pseudo-12
Location	Trials
United States	117
China	27
France	13
Italy	8
United Kingdom	8

Trials by US State

Trials by US State for Pseudo-12
Location	Trials
Texas	11
Massachusetts	6
North Carolina	6
New York	6
Pennsylvania	6

Clinical Trial Progress for Pseudo-12

Clinical Trial Phase

Clinical Trial Phase for Pseudo-12
Clinical Trial Phase	Trials
Phase 4	14
Phase 3	11
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Pseudo-12
Clinical Trial Phase	Trials
Completed	37
Recruiting	25
Not yet recruiting	14

Clinical Trial Sponsors for Pseudo-12

Sponsor Name

Sponsor Name for Pseudo-12
Sponsor	Trials
National Cancer Institute (NCI)	6
Peking Union Medical College Hospital	4
M. Schaefer, MD	2

Sponsor Type

Sponsor Type for Pseudo-12
Sponsor	Trials
Other	141
Industry	24
NIH	10

Clinical Trials, Market Analysis, and Projections for Targeted Therapies: A Focus on KRAZATI (adagrasib)

Introduction

The landscape of clinical trials and pharmaceutical market dynamics is evolving rapidly, driven by advancements in targeted therapies. One such therapy that has garnered significant attention is KRAZATI (adagrasib), developed by Bristol Myers Squibb, which targets the KRAS G12C mutation in various cancers. Here, we delve into the clinical trials update, market analysis, and projections for this groundbreaking drug.

Clinical Trials Update: KRAZATI (adagrasib)

KRYSTAL-12 Trial

The pivotal Phase 3 KRYSTAL-12 study has been a cornerstone in the clinical development of KRAZATI. This open-label, multicenter, randomized trial compares KRAZATI as a monotherapy to standard-of-care chemotherapy in patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)[1].

• Primary Endpoint: The trial has met its primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR).
• Secondary Endpoints: Key secondary endpoints, including overall response rate (ORR), duration of response (DOR), and overall survival (OS), have also shown promising results.
• Safety Profile: The safety data from the trial is consistent with the known safety profile of KRAZATI, with no new safety signals reported.

Other Clinical Trials

In addition to the KRYSTAL-12 trial, KRAZATI is being evaluated in various other clinical settings, including advanced colorectal cancer, pancreatic cancer, and other solid tumors. Notably, the U.S. FDA has granted breakthrough therapy designation for KRAZATI in combination with cetuximab for KRAS G12C-mutated advanced colorectal cancer[1].

Market Analysis

Global Clinical Trials Market

The global clinical trials market is projected to grow significantly, driven by the increasing prevalence of chronic diseases and the need for innovative treatments. The market is expected to grow from $61.58 billion in 2024 to $106.78 billion by 2032, at a CAGR of 7.1%[3].

Targeted Therapies Market

Targeted therapies, such as KRAZATI, are a key segment of this growing market. These therapies offer precise treatment options for patients with specific genetic mutations, enhancing efficacy and reducing side effects.

Regional Market Share

North America and Europe are significant players in the clinical trials market, with North America generating a revenue of USD 27.65 billion in 2023. However, the Asia Pacific region is expected to expand at the fastest CAGR during the forecast period, driven by the increasing prevalence of infectious and chronic diseases[3].

Market Projections for KRAZATI

Approval and Regulatory Landscape

KRAZATI was granted accelerated approval by the FDA in 2022 for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. It also received conditional marketing authorization from the MHRA and the European Commission in subsequent years[1].

Market Potential

Given the positive results from the KRYSTAL-12 trial and other ongoing studies, KRAZATI is poised to capture a significant share of the targeted therapy market. The drug's efficacy in treating KRAS G12C-mutated cancers, which are notoriously difficult to treat, positions it as a valuable option for patients and healthcare providers.

Competitive Landscape

The market for targeted therapies is competitive, with several pharmaceutical companies investing heavily in R&D. However, KRAZATI's unique mechanism of action and the robust clinical data supporting its use give it a competitive edge. The FDA's acceptance of the supplemental new drug application (sNDA) for KRAZATI in combination with cetuximab for colorectal cancer further strengthens its market position[1].

Impact on Patients and Healthcare System

Patient Outcomes

The statistically significant and clinically meaningful benefits in PFS and ORR demonstrated by KRAZATI translate into improved patient outcomes. Patients with KRAS G12C-mutated NSCLC now have a more effective treatment option, which can enhance their quality of life and survival rates.

Healthcare System

The introduction of KRAZATI and similar targeted therapies is expected to have a positive impact on the healthcare system. These therapies can reduce the economic burden associated with treating advanced cancers by offering more effective and potentially less costly treatment options in the long run.

Future Directions

Ongoing and Planned Trials

Bristol Myers Squibb continues to evaluate KRAZATI in various clinical settings, including combinations with other anti-cancer therapies. The ongoing INSPIRE trial and other studies will provide further insights into the drug's efficacy and safety profile[1].

Regulatory Discussions

The company plans to discuss the results of the KRYSTAL-12 trial and other studies with health authorities to secure broader approvals and expand the drug's indications. This includes potential NDA submissions based on the clinical data to date[1].

Key Takeaways

• Clinical Success: KRAZATI has demonstrated significant clinical benefits in treating KRAS G12C-mutated NSCLC, meeting primary and key secondary endpoints in the KRYSTAL-12 trial.
• Market Growth: The global clinical trials market and targeted therapies segment are expected to grow substantially, driven by the need for innovative treatments.
• Regulatory Approvals: KRAZATI has received accelerated approval and conditional marketing authorization, with ongoing regulatory discussions to expand its indications.
• Patient Impact: The drug offers improved patient outcomes, enhancing quality of life and survival rates for those with KRAS G12C-mutated cancers.

FAQs

Q: What is KRAZATI (adagrasib), and how does it work? A: KRAZATI (adagrasib) is a targeted therapy that inhibits the KRAS G12C mutation, a common genetic alteration in certain cancers. It works by selectively binding to the mutated KRAS protein, preventing its activation and thereby inhibiting tumor growth.

Q: What are the key findings from the KRYSTAL-12 trial? A: The KRYSTAL-12 trial showed that KRAZATI demonstrated a statistically significant and clinically meaningful benefit in progression-free survival (PFS) and overall response rate (ORR) compared to standard-of-care chemotherapy.

Q: What other cancers is KRAZATI being evaluated for? A: In addition to NSCLC, KRAZATI is being evaluated for advanced colorectal cancer, pancreatic cancer, and other solid tumors.

Q: What regulatory approvals has KRAZATI received? A: KRAZATI has received accelerated approval from the FDA and conditional marketing authorization from the MHRA and the European Commission.

Q: How does KRAZATI impact patient outcomes? A: KRAZATI improves patient outcomes by offering a more effective treatment option for KRAS G12C-mutated cancers, enhancing quality of life and survival rates.

Sources

1. Bristol Myers Squibb: "Bristol Myers Squibb Announces Pivotal KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets Primary Endpoint of Progression-Free Survival for Patients with Pretreated KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer."
2. PharmChek: "The Rise of Super Meth: The Destructive Effects of P2P Methamphetamine."
3. Fortune Business Insights: "Clinical Trials Market Size, Share, Industry Trends, Growth, 2032."
4. Applied Therapeutics: "Applied Therapeutics Announces Positive Results from 12-month Interim Analysis of Govorestat (AT-007) in the Ongoing INSPIRE Phase 3 Trial in Patients with SORD Deficiency."
5. Aidan Hollis: "The Anti-Competitive Effects of Brand-Controlled “Pseudo-Generics” in the Pharmaceutical Market."

Last updated: 2025-01-07