Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET)

A Single-Arm, Open-Label, Exploratory Mechanistic Validation (PoM) Clinical Trial of Toludesvenlafaxine Hydrochloride Extended-Release Tablets Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain Using 11C-CFT Positron Emission Tomography (PET)

This study was a single-arm, open-label clinical study to assess dopamine transporter occupancy in the brain of patients with depression using 11C-CFT positron emission tomography (PET).

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Toludesvenlafaxine hydrochloride sustained-release tablets

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: YIFENG SHEN, MD; Phone Number: +8618017311040; Email: shenyifeng@yahoo.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Yifeng SHEN, MD; Phone Number: 86-21-34773657; Email: shenyifeng@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female outpatients aged 18 years and older;
• Meet DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) diagnostic criteria for depression (296.2/296.3), and not accompanied by psychotic features;
• A Montgomery - Asberg Depression Rating Scale (MADRS) total score ≥ 26 at screening;
• Anhedonia scale score < 28.5 at screening;
• Subjects and their partners take effective non-drug contraceptive measures (such as abstinence and condom with intravaginal spermicide) throughout the study and within 6 months after the end of the study, and have no sperm donation plan;
• The subject is willing to participate in the trial and sign the informed consent form and is able to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

• Known to have a history of allergy to any component of the investigational drug or similar drugs, or allergic constitution (defined as allergy to two or more drugs or food) and the investigator determines that it is not appropriate to participate in the trial;
• Significant suicide attempt or behavior, MADRS scale item 10 (suicidal ideation) score ≥ 4 points;
• Pregnant or lactating women, recently planned pregnancy;
• Those who meet DSM-5 diagnosis of schizophrenia spectrum or other psychoses, bipolar or related disorders, obsessive-compulsive and related disorders, traumatic and stress-related disorders, dissociative disorders, anorexia nervosa or bulimia, personality disorders, substance-related or alcohol use disorders (except nicotine or caffeine);
• Patients with depression secondary to other mental or physical diseases or with a past medical history or family history of movement disorders (such as Parkinson's disease);
• Receipt of any contrast agent or radiopharmaceutical within 48 hours before the application of the trial drug, or planned application of contrast agent within 24 hours after the administration of the trial drug;
• Contraindications to PET or MRI (magnetic resonance imaging) (including claustrophobia, alcohol allergy, cardiac pacemaker and neurostimulator in the body, metal foreign body or tracer component allergy, etc.); in the past 10 years,Major occupational exposure to ionizing radiation (e.g., more than 50 nanovolts/year) or exposure to radioactive substances or ionizing radiation for therapeutic or research purposes;
• Patients who stopped antidepressant drugs for less than 7 half-lives (at least 2 weeks for monoamine oxidase inhibitors and at least 1 month for fluoxetine) before entering the group;
• History of gastrointestinal disease known to interfere with drug absorption or excretion or history of surgery known to interfere with drug absorption or excretion;
• History of increased intraocular pressure or narrow glaucoma;
• Total bilirubin (TBIL) value 1.5 times higher than the upper limit of normal, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times higher than the upper limit of normal, thyroid stimulating hormone (TSH) higher than the normal range or glomerular filtration rate (GFR) ≤ 70 mL/min at screening or baseline;
• Patients with serious unstable cardiovascular disease, liver disease, kidney disease, blood disease, endocrine disease, central nervous system and other physical diseases or medical history, or the subjects are not suitable for the study judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toludesvenlafaxine hydrochloride sustained-release tablets; 40 mg/tablet, 80mg/tablet, 40 mg~160mg each time, once a day, for 42 days

Drug: Toludesvenlafaxine hydrochloride sustained-release tablets; D1~D6, 40mg/ tablet, 1 tablet per time, once a day, D7~D10, 80mg/ tablet, 1 tablet per time, once a day, D11~D42, 80mg/ tablet, 2 tablets per time, once a day. For subjects who cannot tolerate 160mg, the dose may be reduced to 80mg/ dose once daily. After the number of subjects receiving 160mg/ dose reached 6, the remaining subjects received D11~D42, 80mg/ tablet, one tablet each time, once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Dopamine Transporters Occupancy in the Basal Ganglia（Positron emission tomography with 11C-CFT） was determine by SUVr of the Basal Ganglia DAT.	from baseline to day 14 and 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in the total score of 10 items on the Montgomery-Asperger's Depression Scale (MADRS) from baseline	from baseline to day 42
Changes in the Scores anhedonia	from baseline to day 42
Incidence Rate of Adverse event	from baseline to day 42

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Yantai University
• Investigators: Principal Investigator: Yifeng SHEN, MD, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: SMHC-235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No