Efficacy and Safety Study of Levomilnacipran Hydrochloride Extended-Release Capsules in Major Depressive Disorder

NCT07253207 | Completed Phase 3

• 1 other identifier: HH-ZMNPL-2024
• Study Type: interventional
• Target: 392
• Locations: 1 country
• Sites: 28

Brief Summary

The purpose of this study is using Duloxetine Hydrochloride Enteric Capsules as the positive control, to evaluate the efficacy and safety of Levomilnacipran Hydrochloride Extended-Release Capsules in patients with Major Depressive Disorder (MDD).

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• The change from baseline in the total score of the 17-item Hamilton Depression Rating Scale (HAM-D17) after 8 weeks of treatment.

  Change from baseline at Week 8 in total score of the 17-item Hamilton Depression Rating Scale (HAM-D17) (Score range: 0-52; a higher score indicates greater severity of depressive symptoms.)

  8 weeks of treatment

Study Arms (2)

Duloxetine Hydrochloride Enteric Capsules

ACTIVE COMPARATOR

Drug: Duloxetine Hydrochloride Enteric Capsules

Levomilnacipran Hydrochloride Extended-Release Capsules

EXPERIMENTAL

Drug: Levomilnacipran Hydrochloride Extended-Release Capsules

Interventions

Levomilnacipran Hydrochloride Extended-Release Capsules DRUG

Treatment period: 1. Levomilnacipran Hydrochloride Extended-Release Capsules 20mg/day is to be given orally, once daily, for 1-2 days in the first week of treatment. 2. Levomilnacipran Hydrochloride Extended-Release Capsules 40mg/day is to be given orally, once daily, for 3-7 days in the first week of treatment. 3. Levomilnacipran Hydrochloride Extended-Release Capsules 80mg/day is to be given orally, once daily, for the second week of treatment. 4. Levomilnacipran Hydrochloride Extended-Release Capsules 40, 80 or 120mg/day (the dosage based on the participant's clinical response and tolerance) is to be given orally, once daily, for the weeks 3 to 8 of treatment. Reduction period: Dosage of 20-80mg/day based on the tolerable dose during the 8th week of treatment.

Levomilnacipran Hydrochloride Extended-Release Capsules

Duloxetine Hydrochloride Enteric Capsules DRUG

Treatment period: Duloxetine Hydrochloride Enteric Capsules 60mg/day is to be given orally, once daily, for 8 weeks. Reduction period: Duloxetine Hydrochloride Enteric Capsules 60mg/day is to be given orally, once daily, for 2 weeks.

Duloxetine Hydrochloride Enteric Capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient patients aged 18 to 65 years (inclusive of 18 but exclusive of 65), regardless of gender;
• Meet the diagnostic criteria for depression as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a duration of at least 3 months for first-episode cases (30 days per month);
• Current depressive episode confirmed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) version 7.0.0 or higher;
• Total HAMD17 score ≥18 at screening and baseline visits;
• CGI-S score ≥4 at screening and baseline visits;
• Agree to use effective contraception during the trial and for 30 days after the last dose (women of childbearing potential must have a negative pregnancy test before dosing and not be breastfeeding), and men and women must have no plans to donate sperm or eggs, respectively;
• Voluntarily participate in the trial and sign the informed consent form.

You may not qualify if:

• Meet DSM-5 diagnostic criteria for other mental disorders (including but not limited to schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, obsessive-compulsive and related disorders, somatic symptom and related disorders);
• Previous failure to respond to adequate dose and duration (maximum recommended dose for MDD as per label for at least 4 weeks) of serotonin and norepinephrine reuptake inhibitors (including but not limited to milnacipran, levomilnacipran, duloxetine, venlafaxine, desvenlafaxine), or failure to respond to adequate dose and duration of at least two antidepressant drugs;
• Allergic to milnacipran, levomilnacipran, duloxetine, or excipients of the trial drug, or have an allergic constitution;
• History of suicide attempt within 1 year prior to screening; suicidal or self-harming behavior during screening; HAMD17 item 3 (suicide) score ≥3; currently at high suicide risk;
• Depression secondary to other diseases;
• History of epileptic seizures (except for febrile convulsions in childhood);
• Received systematic electroconvulsive therapy, transcranial magnetic stimulation, transcranial direct current stimulation, systematic psychotherapy, or other treatments with antidepressant effects within 3 months prior to screening; received electroconvulsive therapy within 1 month prior to screening;
• Discontinuation of psychotropic drugs or their active metabolites less than 5 half-lives, or monoamine oxidase inhibitors less than 2 weeks, before randomization;
• Required to use drugs with clinically significant interactions with the trial drug during the trial (including but not limited to monoamine oxidase inhibitors, other serotonergic drugs, drugs affecting coagulation, strong CYP3A4/CYP1A2/CYP2D6 inhibitors or inducers, alcohol, linezolid, and intravenous methylene blue);
• Conditions affecting drug swallowing or absorption, as judged by the investigator;
• Risk factors for angle-closure glaucoma, as judged by the investigator;
• Abnormal and clinically significant results from physical examinations or laboratory tests at screening or baseline, as judged by the investigator, including but not limited to ALT, AST, total bilirubin, or serum creatinine \>1.5 times the upper limit of normal, or thyroid-stimulating hormone outside the normal range;
• Current or past medical history of diseases or dysfunctions affecting the trial, as judged by the investigator, including but not limited to chronic or acute diseases of the nervous, motor, circulatory, respiratory, digestive, urinary, endocrine, reproductive, or immune systems;
• Clinically significant cardiovascular diseases, as judged by the investigator, including but not limited to atrial fibrillation, second- or third-degree atrioventricular block, myocardial infarction within 12 months, or NYHA heart function class III or above;
• ECG QTcF interval ≥450 ms (males) or ≥470 ms (females), or other factors increasing the risk of QTcF prolongation or arrhythmic events (including but not limited to heart failure, hypokalemia, family history of long QT syndrome), or ECG heart rate \<50 bpm or \>120 bpm (Note: QTcF = QT/(RR\^0.33));

Sponsors & Collaborators

• Zhejiang Huahai Pharmaceutical Co., Ltd.: lead

Study Sites (28)

Hefei Fourth People's Hospital

Hefei, Anhui, 230031, China

Location

Wuhu Hospital of Beijing Anding Hospital, Capital Medical University

Wuhu, Anhui, 241003, China

Location

Beijing Anding Hospital Capital Medical University

Beijing, Beijing Municipality, 100000, China

Location

Beijing HuiLongGuan Hospital

Beijing, Beijing Municipality, 102200, China

Location

Chongqing Mental Health Center

Chongqing, Chongqing Municipality, 401147, China

Location

Affiliated Brain Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510370, China

Location

Hebei Provincial Mental Health Center

Baoding, Hebei, 071030, China

Location

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

Location

Hunan Provincial Second People's Hospital

Changsha, Hunan, 410007, China

Location

Nantong Mental Health Center

Nantong, Jiangsu, 226005, China

Location

Suzhou Guangji Hospital

Suzhou, Jiangsu, 215131, China

Location

Wuxi Mental Health Center

Wuxi, Jiangsu, 214000, China

Location

Zhenjiang Mental Health Center

Zhenjiang, Jiangsu, 212021, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Jiangxi Provincial Psychiatric Hospital

Nanchang, Jiangxi, 330029, China

Location

Jilin Provincial Neuropsychiatric Hospital

Siping, Jilin, 136000, China

Location

The First Affiliated Hospital of Xi 'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Xi 'an Mental Health Center

Xi'an, Shaanxi, 710199, China

Location

Shandong Provincial Mental Health Center

Jinan, Shandong, 250014, China

Location

Shanghai Pudong New Area Mental Health Center

Shanghai, Shanghai Municipality, 200124, China

Location

Linfen Central Hospital

Linfen, Shanxi, 041099, China

Location

The First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

Chengdu Fourth People's Hospital

Chengdu, Sichuan, 610041, China

Location

Tianjin Fourth Central Hospital

Tianjin, Tianjin Municipality, 300074, China

Location

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

Location

Hangzhou Seventh People's Hospital

Hangzhou, Zhejiang, 310007, China

Location

Huzhou Third People's Hospital

Huzhou, Zhejiang, 313000, China

Location

Ningbo University Affiliated Kangning Hospital

Ningbo, Zhejiang, 315201, China

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 28, 2025
• Study Start: October 17, 2024
• Primary Completion: June 13, 2025
• Study Completion: July 22, 2025
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

CN (28)