search
Back to results

Study of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression

Primary Purpose

Major Depressive Disorder (MDD)

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Ammoxetine hydrochloride enteric-coated tablets
Duloxetine hydrochloride enteric-coated capsules
Placebo to Ammoxetine
Placebo to Duloxetine
Sponsored by
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder (MDD)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Subjects aged 18 and 65 years (inclusive), no gender limitation;
  • 2. Subject has recurrent Major Depressive Disorder (MDD) as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 5th Edition), single episode or recurrent episodes (DSM-IV-TR criteria, classification code 296.2/296.3), without psychotic symptoms;
  • 3. Subjects with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 26 and subjects with Clinical Global Impression Scale Disease Severity CGI-S severity score ≥ 4 at screening and baseline;
  • 4. For male or female with fertility: must agree to use effective contraceptive method during the study and within 1 month after the end of the trial;
  • 5. Be able to read and understand the content of the informed consent and voluntarily sign the informed consent.

Exclusion Criteria:

  • 1. Subjects with ≥ 25% reduction in MADRS score in the baseline period compared to the screening period;
  • 2. Subjects meet DSM-5 diagnostic criteria for other mental disorders (schizophrenia spectrum and other psychiatric disorders, bipolar and related disorders, anxiety disorders, obsessive-compulsive and related disorders, somatic symptoms and related disorders, etc.);
  • 3. Subjects are diagnosed as DSM-5 drug use disorder;
  • 4. Refractory depression (subjects who had previously used two different mechanisms of antidepressants and failed after receiving adequate treatment (at least 8 weeks);
  • 5. Organic mental disorders, such as depression caused by hypothyroidism;
  • 6. Depression caused by psychoactive substances or non-addictive substances;
  • 7. Subjects with other diseases or other types of mental disorders with depressive symptoms;
  • 8. Subjects assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) and those judged by the investigator to be at risk for suicide, or to have engaged in suicidal behaviour within 6 months prior to screening;
  • 9. Allergic constitution (e.g. allergic to two or more drugs or to serotonin norepinephrine reuptake inhibitors (SNRIs));
  • 10.Previous history of malignant tumor;
  • 11.Previous history of elevated intraocular pressure or narrow angle glaucoma;
  • 12.Subjects suffered from other serious physical diseases, such as uncontrolled hypertension or unstable cardiovascular disease, serious liver disease, kidney disease, blood disease, endocrine disease, neurological disease, etc;
  • 13.Subjects with diseases that interfere with the absorption of oral medications, such as active bowel disease, partial or complete intestinal obstruction, chronic diarrhea, etc;
  • 14.Subjects who have used drugs or foods that alter the activity of liver enzymes (CYP2C19 and CYP3A4) such as dexamethasone, rifampicin, omeprazole, grapefruit, etc., within 4 weeks prior to screening;
  • 15.12-lead ECG system showed degree II or III atrioventricular block, long QT syndrome or QTc > 450 ms (male) / 470 ms (female) at screening;
  • 16.Subjects discontinued use of a combination of drugs that prolong the QT interval prior to randomization, or drugs that can cause prolongation of the QT and may induce TdP for less than 5 half-lives of the drugs;
  • 17.In screening period, subjects with ALT or AST 1.5 times higher than the upper limit of laboratory normal value; creatinine 1.1 times higher than the upper limit of normal value; and abnormalities in 2 or more of the 5 indicators of thyroid function (TSH, FT3, FT4, TT3 or TT4 0.9 times below the lower limit of normal value or 1.1 times above the upper limit of normal value);
  • 18.Subjects have used monoamine oxidase inhibitors within 2 weeks before randomization;
  • 19.Subjects discontinuing antipsychotics, antidepressants or mood stabilizers for less than 5 half-lives of the drug before randomization;
  • 20.Subjects who are using long half-life drugs (such as fluoxetine, long-acting antipsychotics, etc.);
  • 21.Subjects who have received electroconvulsive therapy (ECT), systematic psychotherapy (interpersonal relationship therapy, dynamic therapy, cognitive behavior therapy, etc.), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), phototherapy, etc. within 3 months before screening, or subjects who, in the judgment of the investigator, are currently in need of such treatment;
  • 22.Female subjects who are breastfeeding or have a positive pregnancy test during the screening period or during the study;
  • 23.Alcohol or drug dependence within 3 months before screening;
  • 24.Subjects who have participated in other clinical trials within 3 months before screening and are taking the test drug;
  • 25.Subjects who, in the opinion of the investigator, have any other condition that makes them unsuitable for participation in this trial.

Sites / Locations

  • Shanghai Mental Health CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Duloxetine group

Placebo group

Ammoxetine group-cohort 1

Ammoxetine group-cohort 2

Ammoxetine group-cohort 3

Ammoxetine group-cohort 4

Arm Description

The eligible subjects will receive duloxetine hydrochloride enteric-coated capsules plus placebo to Ammoxetine.

The eligible subjects will receive placebo to Ammoxetine and placebo to Duloxetine.

The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.

The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.

The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.

The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.

Outcomes

Primary Outcome Measures

Change from baseline in Montgomery Asperger Depression Scale (MADRS) score at the end of treatment (week 6)
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement. Change = (Week 6 post-dose score - baseline week 0 score). at the end of treatment (week 6)

Secondary Outcome Measures

Change from baseline in Hamilton Depression Scale (HAMD-17) at week 1, 2, 4, 6
The HAMD-17 is a 17-item, clinician-rated scale that assesses depressive symptoms. The HAMD-17 consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAMD-17 scores indicate more severe depression. Change = (Week 1, 2, 4 and 6 post-dose score - baseline week 0 score).
Change from baseline in Hamilton Anxiety Inventory (HAMA) scores at week 1, 2, 4, 6
The HAMA is used as a rating measure of anxiety severity. The scale consists of 14 items. Each item is rated on a scale of 0 to 4. The HAMA total score is the sum of the 14 items and the score ranges from 0 to 56, 0 is considered the best outcome. Change = (Week 1, 2, 4 and 6 post-dose score - baseline week 0 score).
Change from baseline in CGI-S score at week 1, 2, 4, 6,7
The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment. The CGI-S will provide an overall clinician-determined summary measure that takes into account all available information including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. Change = (Week 1, 2, 4, 6 and 7 post-dose score - baseline week 0 score).
The percentage of subjects with a MARDS score reduction ≥ 25%
The score reduction rate is defined as (screening period MARDS scale score - post-dose MARDS scale score)/screening period MARDS scale score x 100%.
Incidence of adverse events (AE)
The AEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.
Change from baseline in MADRS score at week 1, 2, 4
Change = (Week 1, 2 and 4 post-dose score - baseline week 0 score).

Full Information

First Posted
July 30, 2021
Last Updated
November 10, 2021
Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05018013
Brief Title
Study of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression
Official Title
Efficacy and Safety of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression: A Multicenter, Randomized, Double-blind, Double-dummy, Active- and Placebo-controlled, Parallel-group, Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 21, 2021 (Actual)
Primary Completion Date
August 1, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Ammoxetine hydrochloride enteric-coated tablets in subjects with depression.
Detailed Description
In this study, a randomized, double-blind, duloxetine hydrochloride enteric coated capsule positive and placebo-controlled multicenter study was used to evaluate the efficacy and safety of different doses of amxetine hydrochloride enteric coated tablets in the treatment of depression.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder (MDD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Duloxetine group
Arm Type
Active Comparator
Arm Description
The eligible subjects will receive duloxetine hydrochloride enteric-coated capsules plus placebo to Ammoxetine.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
The eligible subjects will receive placebo to Ammoxetine and placebo to Duloxetine.
Arm Title
Ammoxetine group-cohort 1
Arm Type
Experimental
Arm Description
The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.
Arm Title
Ammoxetine group-cohort 2
Arm Type
Experimental
Arm Description
The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.
Arm Title
Ammoxetine group-cohort 3
Arm Type
Experimental
Arm Description
The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.
Arm Title
Ammoxetine group-cohort 4
Arm Type
Experimental
Arm Description
The eligible subjects will receive Ammoxetine hydrochloride enteric-coated tablets plus placebo to Duloxetine.
Intervention Type
Drug
Intervention Name(s)
Ammoxetine hydrochloride enteric-coated tablets
Other Intervention Name(s)
Ammoxetine
Intervention Description
Ammoxetine hydrochloride enteric-coated tablets
Intervention Type
Drug
Intervention Name(s)
Duloxetine hydrochloride enteric-coated capsules
Other Intervention Name(s)
Duloxetine
Intervention Description
Duloxetine hydrochloride enteric-coated capsules
Intervention Type
Drug
Intervention Name(s)
Placebo to Ammoxetine
Other Intervention Name(s)
Placebo
Intervention Description
Placebo to Ammoxetine
Intervention Type
Drug
Intervention Name(s)
Placebo to Duloxetine
Other Intervention Name(s)
Placebo
Intervention Description
Placebo to Duloxetine
Primary Outcome Measure Information:
Title
Change from baseline in Montgomery Asperger Depression Scale (MADRS) score at the end of treatment (week 6)
Description
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement. Change = (Week 6 post-dose score - baseline week 0 score). at the end of treatment (week 6)
Time Frame
Baseline and week 6
Secondary Outcome Measure Information:
Title
Change from baseline in Hamilton Depression Scale (HAMD-17) at week 1, 2, 4, 6
Description
The HAMD-17 is a 17-item, clinician-rated scale that assesses depressive symptoms. The HAMD-17 consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAMD-17 scores indicate more severe depression. Change = (Week 1, 2, 4 and 6 post-dose score - baseline week 0 score).
Time Frame
Baseline, week 1, 2, 4 and 6
Title
Change from baseline in Hamilton Anxiety Inventory (HAMA) scores at week 1, 2, 4, 6
Description
The HAMA is used as a rating measure of anxiety severity. The scale consists of 14 items. Each item is rated on a scale of 0 to 4. The HAMA total score is the sum of the 14 items and the score ranges from 0 to 56, 0 is considered the best outcome. Change = (Week 1, 2, 4 and 6 post-dose score - baseline week 0 score).
Time Frame
Baseline, week 1, 2, 4 and 6
Title
Change from baseline in CGI-S score at week 1, 2, 4, 6,7
Description
The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment. The CGI-S will provide an overall clinician-determined summary measure that takes into account all available information including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. Change = (Week 1, 2, 4, 6 and 7 post-dose score - baseline week 0 score).
Time Frame
Baseline, week 1, 2, 4, 6 and 7
Title
The percentage of subjects with a MARDS score reduction ≥ 25%
Description
The score reduction rate is defined as (screening period MARDS scale score - post-dose MARDS scale score)/screening period MARDS scale score x 100%.
Time Frame
Week 1 and 2
Title
Incidence of adverse events (AE)
Description
The AEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.
Time Frame
Throughout the study period,an average of 18 months
Title
Change from baseline in MADRS score at week 1, 2, 4
Description
Change = (Week 1, 2 and 4 post-dose score - baseline week 0 score).
Time Frame
baseline, week 1, 2 and 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Subjects aged 18 and 65 years (inclusive), no gender limitation; 2. Subject has recurrent Major Depressive Disorder (MDD) as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 5th Edition), single episode or recurrent episodes (DSM-IV-TR criteria, classification code 296.2/296.3), without psychotic symptoms; 3. Subjects with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 26 and subjects with Clinical Global Impression Scale Disease Severity CGI-S severity score ≥ 4 at screening and baseline; 4. For male or female with fertility: must agree to use effective contraceptive method during the study and within 1 month after the end of the trial; 5. Be able to read and understand the content of the informed consent and voluntarily sign the informed consent. Exclusion Criteria: 1. Subjects with ≥ 25% reduction in MADRS score in the baseline period compared to the screening period; 2. Subjects meet DSM-5 diagnostic criteria for other mental disorders (schizophrenia spectrum and other psychiatric disorders, bipolar and related disorders, anxiety disorders, obsessive-compulsive and related disorders, somatic symptoms and related disorders, etc.); 3. Subjects are diagnosed as DSM-5 drug use disorder; 4. Refractory depression (subjects who had previously used two different mechanisms of antidepressants and failed after receiving adequate treatment (at least 8 weeks); 5. Organic mental disorders, such as depression caused by hypothyroidism; 6. Depression caused by psychoactive substances or non-addictive substances; 7. Subjects with other diseases or other types of mental disorders with depressive symptoms; 8. Subjects assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) and those judged by the investigator to be at risk for suicide, or to have engaged in suicidal behaviour within 6 months prior to screening; 9. Allergic constitution (e.g. allergic to two or more drugs or to serotonin norepinephrine reuptake inhibitors (SNRIs)); 10.Previous history of malignant tumor; 11.Previous history of elevated intraocular pressure or narrow angle glaucoma; 12.Subjects suffered from other serious physical diseases, such as uncontrolled hypertension or unstable cardiovascular disease, serious liver disease, kidney disease, blood disease, endocrine disease, neurological disease, etc; 13.Subjects with diseases that interfere with the absorption of oral medications, such as active bowel disease, partial or complete intestinal obstruction, chronic diarrhea, etc; 14.Subjects who have used drugs or foods that alter the activity of liver enzymes (CYP2C19 and CYP3A4) such as dexamethasone, rifampicin, omeprazole, grapefruit, etc., within 4 weeks prior to screening; 15.12-lead ECG system showed degree II or III atrioventricular block, long QT syndrome or QTc > 450 ms (male) / 470 ms (female) at screening; 16.Subjects discontinued use of a combination of drugs that prolong the QT interval prior to randomization, or drugs that can cause prolongation of the QT and may induce TdP for less than 5 half-lives of the drugs; 17.In screening period, subjects with ALT or AST 1.5 times higher than the upper limit of laboratory normal value; creatinine 1.1 times higher than the upper limit of normal value; and abnormalities in 2 or more of the 5 indicators of thyroid function (TSH, FT3, FT4, TT3 or TT4 0.9 times below the lower limit of normal value or 1.1 times above the upper limit of normal value); 18.Subjects have used monoamine oxidase inhibitors within 2 weeks before randomization; 19.Subjects discontinuing antipsychotics, antidepressants or mood stabilizers for less than 5 half-lives of the drug before randomization; 20.Subjects who are using long half-life drugs (such as fluoxetine, long-acting antipsychotics, etc.); 21.Subjects who have received electroconvulsive therapy (ECT), systematic psychotherapy (interpersonal relationship therapy, dynamic therapy, cognitive behavior therapy, etc.), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), phototherapy, etc. within 3 months before screening, or subjects who, in the judgment of the investigator, are currently in need of such treatment; 22.Female subjects who are breastfeeding or have a positive pregnancy test during the screening period or during the study; 23.Alcohol or drug dependence within 3 months before screening; 24.Subjects who have participated in other clinical trials within 3 months before screening and are taking the test drug; 25.Subjects who, in the opinion of the investigator, have any other condition that makes them unsuitable for participation in this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li Yang, MA
Phone
+86-13321898532
Ext
+86-021606739
Email
lcliyang@mail.ecspc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huang Yanli, MD
Organizational Affiliation
CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Li Huafang, Ph.D
Organizational Affiliation
Shanghai Mental Health Center
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai Mental Health Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Huafang, Ph.D
Phone
86-021-34773128

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression

We'll reach out to this number within 24 hrs