CLINICAL TRIALS PROFILE FOR TRINTELLIX

All Clinical Trials for TRINTELLIX

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02969876 ↗	Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine	Terminated	Takeda	Phase 4	2017-08-24	The study is a 6-week, proof-of-concept, open trial of vortioxetine for 20 patients with major depressive disorder.
NCT02969876 ↗	Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine	Terminated	Massachusetts General Hospital	Phase 4	2017-08-24	The study is a 6-week, proof-of-concept, open trial of vortioxetine for 20 patients with major depressive disorder.
NCT02845349 ↗	Vortioxetine for the Treatment of Major Depression and Co-morbidities After Traumatic Brain Injury (TBI)	Withdrawn	Takeda	Phase 3	2016-10-01	Traumatic brain injury (TBI) is a major public health problem with an annual incidence of about 1.7 million per year. TBI is associated with various long-term morbidities. Among them, psychiatric disturbances are the major cause of chronic disability and poor quality of life. Major depression is the common psychiatric sequela post TBI with rates ranging from 13% at 1 year to 60% at 8 years after TBI. Major depression after TBI (henceforth referred to as TBI depression) is often associated with comorbid neuropsychiatric symptoms (NPS) such as anxiety, aggression, substance abuse and cognitive deficits that often makes treatment difficult. Despite increased rates of depression, there is no Food and Drug Administration (FDA) approved drug/s for its treatment. The investigators propose to address these limitations by use of a novel serotonergic agent, vortioxetine, which has a multimodal mechanism of action through serotonin transporter (SERT) inhibition, 5-hydroxytryptamine (5-HT)3, 7, and 1D receptor antagonism, 1B receptor partial agonism, and 1A receptor agonism. Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid NPS. Study Design: The study design will include a DBPCT of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12. Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging.
NCT02845349 ↗	Vortioxetine for the Treatment of Major Depression and Co-morbidities After Traumatic Brain Injury (TBI)	Withdrawn	Johns Hopkins University	Phase 3	2016-10-01	Traumatic brain injury (TBI) is a major public health problem with an annual incidence of about 1.7 million per year. TBI is associated with various long-term morbidities. Among them, psychiatric disturbances are the major cause of chronic disability and poor quality of life. Major depression is the common psychiatric sequela post TBI with rates ranging from 13% at 1 year to 60% at 8 years after TBI. Major depression after TBI (henceforth referred to as TBI depression) is often associated with comorbid neuropsychiatric symptoms (NPS) such as anxiety, aggression, substance abuse and cognitive deficits that often makes treatment difficult. Despite increased rates of depression, there is no Food and Drug Administration (FDA) approved drug/s for its treatment. The investigators propose to address these limitations by use of a novel serotonergic agent, vortioxetine, which has a multimodal mechanism of action through serotonin transporter (SERT) inhibition, 5-hydroxytryptamine (5-HT)3, 7, and 1D receptor antagonism, 1B receptor partial agonism, and 1A receptor agonism. Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid NPS. Study Design: The study design will include a DBPCT of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12. Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging.
NCT02234362 ↗	Vortioxetine for Menopausal Depression	Completed	Takeda Pharmaceuticals North America, Inc.	Phase 4	2015-06-12	The broad goal of this study was to examine the efficacy and tolerability of vortioxetine (flexible dose) for the treatment of major depressive disorder (MDD) in symptomatic women around the menopausal transition. We hypothesized that an eight-week treatment with vortioxetine would promote a significant improvement of depression symptoms and other menopause-related physical symptoms.
NCT02234362 ↗	Vortioxetine for Menopausal Depression	Completed	Massachusetts General Hospital	Phase 4	2015-06-12	The broad goal of this study was to examine the efficacy and tolerability of vortioxetine (flexible dose) for the treatment of major depressive disorder (MDD) in symptomatic women around the menopausal transition. We hypothesized that an eight-week treatment with vortioxetine would promote a significant improvement of depression symptoms and other menopause-related physical symptoms.
NCT02332954 ↗	Assessment in Work Productivity and the Relationship With Cognitive Symptoms in Patients With MDD Taking Vortioxetine	Completed	Lundbeck Canada Inc.	Phase 4	2015-02-01	The purpose of the study is to describe the association/correlation between change in patient-reported cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a Major Depressive Episode (MDE).

Clinical Trial Conditions for TRINTELLIX

Condition Name

Condition Name for TRINTELLIX
Intervention	Trials
Major Depressive Disorder	4
Depression	3
Major Depression	2
TBI	1

Condition MeSH

Condition MeSH for TRINTELLIX
Intervention	Trials
Depressive Disorder	9
Depression	8
Depressive Disorder, Major	7
Disease	2

Clinical Trial Locations for TRINTELLIX

Trials by Country

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Trials by Country for TRINTELLIX
Location	Trials
Canada	9
United States	5
Mexico	2
Poland	1
India	1

Trials by US State

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−

Trials by US State for TRINTELLIX
Location	Trials
Massachusetts	2
Texas	1
Illinois	1
Missouri	1

Clinical Trial Progress for TRINTELLIX

Clinical Trial Phase

Clinical Trial Phase for TRINTELLIX
Clinical Trial Phase	Trials
Phase 4	7
Phase 3	3
Phase 1	1

Clinical Trial Status

Clinical Trial Status for TRINTELLIX
Clinical Trial Phase	Trials
Completed	3
Unknown status	3
Not yet recruiting	2

Clinical Trial Sponsors for TRINTELLIX

Sponsor Name

Sponsor Name for TRINTELLIX
Sponsor	Trials
Takeda	4
Massachusetts General Hospital	2
Noam Soreni	1

Sponsor Type

Sponsor Type for TRINTELLIX
Sponsor	Trials
Other	10
Industry	8

Clinical Trials and Efficacy of Trintellix

Introduction to Trintellix

Trintellix, also known as vortioxetine, is an antidepressant medication approved for the treatment of major depressive disorder (MDD) in adults. Here, we will delve into the clinical trials that have established its efficacy, as well as provide an update on its market performance and projections.

Clinical Trials Overview

The efficacy of Trintellix has been extensively evaluated in several clinical trials.

Short-Term Efficacy Studies

In 11 pivotal, short-term (6- to 8-week) randomized, double-blind, placebo-controlled Phase III studies, Trintellix demonstrated significant relief in reducing the overall symptoms of MDD. These studies involved more than 3,000 patients and used the Montgomery Asberg Depression Rating Scale (MADRS) or the 24-item Hamilton Depression Rating Scale (HAM-D24) as primary efficacy endpoints. In each study, at least one dose of Trintellix (5 mg/day, 10 mg/day, 15 mg/day, or 20 mg/day) was superior to placebo[3].

Long-Term Efficacy and Maintenance

The long-term efficacy of Trintellix was evaluated in a 48-week, two-phase study. In the initial open-label phase, patients were treated with Trintellix 10 mg/day for 16 weeks. Those who achieved remission were then randomized to Trintellix (5 mg/day, 10 mg/day, or 20 mg/day) or placebo for 32 weeks. The results showed that Trintellix significantly reduced the risk of recurrence of depressive episodes compared to placebo[1][3].

Cognitive Function

In addition to its antidepressant effects, Trintellix has been shown to improve cognitive function in patients with MDD. The FOCUS and CONNECT studies, two eight-week randomized, double-blind, placebo-controlled trials, demonstrated that Trintellix improved performance on the Digit Symbol Substitution Test (DSST), a measure of processing speed, an important aspect of cognitive function often impaired in MDD[4].

Safety and Tolerability

Trintellix has been found to have a favorable safety profile. It does not significantly affect body weight or vital signs such as blood pressure and heart rate. However, some reports of weight gain have been noted post-approval. The drug can be taken with or without food, and no dose adjustment is necessary for patients with mild, moderate, or severe renal impairment, although caution is recommended[3][4].

Market Analysis and Projections

Current Market Performance

Trintellix, marketed as Brintellix in some regions, has shown strong performance in the market. In the first half of 2024, the revenue from Brintellix/Trintellix reached DKK 2,351 million, representing an 11% growth in constant exchange rates (CER) and 9% in Danish kroner (DKK). This growth was driven by increased demand and market share gains in regions such as Europe and the U.S.[2].

Regional Performance

• United States: Sales growth in the U.S. was driven by price increases and higher demand, contributing to a 5% growth in revenue for Trintellix[2].
• Europe: The drug saw significant growth in Europe, particularly in countries like Spain, Italy, and Japan, with a 16% CER growth[2].
• International Markets: Trintellix also performed well in international markets, including Canada and Brazil, though the growth was more modest at 10% CER[2].

Market Projections

Given the strong performance of Trintellix, market projections indicate continued growth. Lundbeck's strategic brands, including Trintellix, are expected to drive revenue growth, with the company's overall revenue increasing by 7% CER in the first quarter of 2024. The growth of Trintellix is anticipated to be sustained by its established efficacy, favorable safety profile, and expanding market presence[2][5].

Competitive Landscape

Trintellix operates in a competitive antidepressant market, but its unique profile, including its positive effects on cognitive function, sets it apart. The inclusion of data from the FOCUS and CONNECT studies in the U.S. labeling has provided additional clinical information, enhancing its appeal to healthcare professionals and patients[4].

Key Takeaways

• Efficacy: Trintellix has demonstrated significant efficacy in reducing symptoms of MDD in both short-term and long-term studies.
• Cognitive Function: It improves cognitive function, particularly processing speed, in patients with MDD.
• Safety: The drug has a favorable safety profile with no significant effects on body weight or vital signs.
• Market Performance: Strong revenue growth in the U.S., Europe, and international markets.
• Projections: Expected continued growth driven by its established efficacy and expanding market presence.

FAQs

What is Trintellix used for?

Trintellix is used for the treatment of major depressive disorder (MDD) in adults.

What are the primary efficacy endpoints in Trintellix clinical trials?

The primary efficacy endpoints are the mean change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) or the 24-item Hamilton Depression Rating Scale (HAM-D24) total score[3].

Does Trintellix affect cognitive function in patients with MDD?

Yes, Trintellix has been shown to improve cognitive function, particularly processing speed, as measured by the Digit Symbol Substitution Test (DSST)[4].

Is Trintellix safe for long-term use?

Trintellix has been evaluated in long-term studies and has been found to maintain efficacy with a favorable safety profile. However, periodic re-evaluation of its usefulness is recommended[3].

How has Trintellix performed in the market?

Trintellix has shown strong revenue growth in the U.S., Europe, and international markets, driven by increased demand and market share gains[2].

Sources

1. Clinical Data | TRINTELLIX (vortioxetine)
   • https://www.trintellixhcp.com/clinical-data
2. Lundbeck Q2 2024 Financial Report
   • https://www.lundbeck.com/content/dam/lundbeck-com/masters/global-site/global-site/investors/financial-events/q22024/Q2%202024_Final.pdf
3. Summary Basis of Decision for Trintellix
   • https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD00197
4. TRINTELLIX® (vortioxetine) Prescribing Information Update
   • https://www.takeda.com/newsroom/newsreleases/2018/trintellix-label-update/
5. Lundbeck Q1 2024 Corporate Release
   • https://www.lundbeck.com/content/dam/lundbeck-com/masters/global-site/global-site/investors/financial-events/q1-2024/Q1%202024_Corporate%20Release_Final.pdf