Efficacy and Safety of S 47445 Versus Placebo as Adjunctive Treatment in Depressed Patients Not Fully Recovered From Depressive Symptoms With a Current Antidepressant Treatment

Efficacy and Safety of S 47445 Versus Placebo as Adjunctive Treatment of Major Depressive Disorder in Patients With an Inadequate Response to Antidepressant Therapy: A Randomised, Double-blind, Placebo Controlled International, Multicentre Study

The purpose of this study is to assess the efficacy and safety of S47445 versus placebo as adjunctive treatment of Major Depressive Disorder in patients with an inadequate response to antidepressant therapy.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: S47445 15mg; Drug: S47445 50mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Mental Health Centre - Plovdiv
  • Sofia, Bulgaria, 1202
    • Mental Health Centre - Sofia district
  • Sofia, Bulgaria, 1606
    • Military Medical Academy, MHAT - Sofia
  • Varna, Bulgaria, 9000
    • Diagnostic Consultative Center "Tchaika"
  • Varna, Bulgaria, 9000
    • Medical center "City clinic"
  • Vratsa, Bulgaria, 3000
    • Mental health centre - Vratsa
• Czechia
  • Brno, Czechia, 602 00
    • Saint Anne s.r.o.
  • Brno, Czechia, 615 00
    • Soukroma psychiatricka ambulance
  • Hradec Kralove, Czechia, 503 41
    • Neuropsychiatrie HK, s.r.o.
  • Litomerice, Czechia, 412 01
    • Bialbi s.r.o.
  • Praha, Czechia, 100 00
    • Clintrial s.r.o.
  • Praha, Czechia, 109 00
    • AD71 s.r.o.
  • Praha, Czechia, 120 00
    • PRAGTIS s.r.o.
  • Praha, Czechia, 160 00
    • Medical Services Prague s.r.o.
  • Strakonice, Czechia, 386 29
    • Psychiatricka ambulance Strakonice
• Finland
  • Helsinki, Finland, 00260
    • Laakarikeskus Mehilainen Psychiatric
  • Kuopio, Finland, 70100
    • Private Practice
  • Oulu, Finland, 90100
    • Oulu Mentalcare Oy, Research Unit
  • Tampere, Finland, 33200
    • Mentoria Oy
• Hungary
  • Baja, Hungary, 6500
    • Bajai Szent Rokus Korhaz, Neurologia/Pszichiátria
  • Balassagyarmat, Hungary, 2660
    • Dr. Kenessey Albert Korhaz-Rendelointezet 1-es Pszihiatriai Osztaly
  • Budapest, Hungary, 1032
    • Forras Outpatient Clinic
  • Budapest, Hungary, 1083
    • Semmelweis Orvostudomanyi Egyetem, Pszichiatriai es Pszichoterapias Klinika
  • Budapest, Hungary, 1135
    • Nyiro Gyula Korhaz, Pszihiatriai Osztaly
  • Budapest, Hungary, 1137
    • Processus Kft., Varoskapu Rendelo
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz, Pszihiatriai, Mentalhygienes es Addiktologiai Osztaly
  • Gyula, Hungary, 5700
    • Bekes Megyei Pandy Kalman Korhaz, Pszihiatriai Osztaly
  • Pecs, Hungary, 7623
    • Pecsi Tudomanyegyetem, Klinikai Kozpont, Pszich. es Pszichoter. Klinika
  • Szeged, Hungary, 6724
    • Szent-Gyorgyi Albert Klinikai Kozpont, Pszichiatriai Klinika
• Russian Federation
  • Moscow, Russian Federation, 109387
    • Psychiatric Hospital N 13
  • Moscow, Russian Federation, 115522
    • Scientific Center of Mental Health, Dpt of Psychiatry N 1
  • Roshchino, Russian Federation, 188820
    • State Budgetary lnstitution of Healthcare Leningrad RPND, In-patient psychiatry department
  • Rostov on don, Russian Federation, 344010
    • Scientific Center for Treatment and Rehabilitation Phoenix, Research department
  • St Petersburg, Russian Federation, 190121
    • Psychoneuropathology Dispensary N 10, Psychiatry dpt
  • St Petersburg, Russian Federation, 191119
    • City Psychiatric Hospital N 4, Psychiatric department
  • St Petersburg, Russian Federation, 192019
    • V.M.Bekhterev Research Institute of Psychoneurology, Department of the neuroses and psychotherapy
• Slovakia
  • Bratislava, Slovakia, 820 07
    • Psychiatricka ambulancia Mentum, s.r.o.
  • Bratislava, Slovakia, 851 01
    • VAVRUSOVA CONSULTING s.r.o., Nestatna psychiatricka ambulancia
  • Kosice, Slovakia, 040 01
    • INVESTA, spol. s r.o., Psychiatricka ambulancia
  • Kysucke Nove Mesto, Slovakia, 024 01
    • Private Practice
  • Rimavska Sobota, Slovakia, 979 01
    • PsychoLine psychiatricka ambulancia s.r.o.
  • Roznava, Slovakia, 048 01
    • NsP Svatej Barbory, Psychiatricke oddelenie
  • Svidnik, Slovakia, 089 01
    • Centrum zdravia R.B.K. s.r.o.
• Ukraine
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology, Department of Borderline and Neurotic Disorders
  • Kherson, Ukraine, 73488
    • Kherson Regional Psychiatric Hospital, Psychiatry department
  • Kyiv, Ukraine, 02660
    • Kyiv Municipal Psychiatric Hospital #2, Department of psychiatry
  • Kyiv, Ukraine, 03049
    • Railway Clinic Hospital #1, Psychoneurological dpt
  • Kyiv, Ukraine, 04080
    • Kyiv Regional Medical Incorporation "Psychiatry", Center of Novel Treatment Rehabilitation Psychotic disorders
  • Kyiv, Ukraine, 04080
    • Ukrainian Research Institut of Social, Forensic Psyshiatry, Department of Therapy
  • Lviv, Ukraine, 79021
    • Lviv District Psychiatric hospital
  • Lviv, Ukraine, 79021
    • Regional Clinic of Psychiatry
  • Odesa, Ukraine, 56014
    • ODESA REGIONAL MEDICAL CENTRE OF MENTAL HEALTHE DAY CARE department
  • Odesa, Ukraine, 65006
    • Odesa Regional Medical Centre of Mental Health Child-adolescens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients
• Fulfilling DSM-5 criteria for Major Depressive Disorder confirmed by the brief structured interview M.I.N.I. (single or recurrent episode, current episode ≤ 12 months, current depressive episode of moderate or severe intensity, with or without anxious distress, with or without melancholic features, without mixed features or atypical features, without seasonal pattern, without psychotic features, without catatonic features, without peripartum onset for the current episode)
• Patients treated for the current depressive episode with an antidepressant treatment with SSRI (fluoxetine, citalopram, paroxetine, escitalopram or sertraline) given in monotherapy at recommended dose for at least 6 weeks and no more than 4 months and with a stable dosage for at least 3 weeks
• HAM-D total score ≥ 20
• Clinical Global Impression Severity of illness (item 1): 6 ≥ CGI-S ≥ 4
• Antidepressant Treatment Response Questionnaire (ATQR) < 50% for the current SSRI
• Absence of any abnormalities likely to interfere with the conduct of the study (ECG, vital signs, laboratory tests, medical history)

Exclusion Criteria:

• Depressive episode of mild intensity according to DSM-5 criteria
• All types of depressive episodes other than those occurring in a Major Depressive Disorder (Persistent Depressive Disorder (Dysthymia) according to DSM-5 criteria, including persistent depressive disorder with intermittent or persistent major depressive episode according to DSM-5, Premenstrual Dysphoric Disorder, Substance Induced Depressive Disorder, Depressive Disorder due to another Medical Condition, Other Specified or Unspecified Depressive Disorder, Bipolar Disorder I or II, depressed episode, Schizoaffective Disorder (Depressive or Bipolar type))
• Depression onset within 12 months after a stroke
• Suicidal risk defined as a score > 3 on the item 3 of the HAM-D scale or in the investigator's opinion
• Lactose intolerance
• Patients with hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
• Resistant depression for the current episode (patients who have not responded to 1 previous antidepressant treatment before the SSRI taken at an appropriate dose)
• Current panic disorder
• Obsessive compulsive disorder
• Current post traumatic stress disorder, current acute stress disorder
• Current or past psychotic disorder
• Any severe personality features

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; One tablet of placebo taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.
Experimental: S47445 15mg	Drug: S47445 15mg; One tablet of S47445 15 mg taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.
Experimental: S47445 50mg	Drug: S47445 50mg; One tablet of S47445 50 mg taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hamilton Depression Rating Scale (HAM-D) total score expressed as change from baseline value	8 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HAM-D total score	Depressive symptoms	at week 0, week 2, week 4, week 6 and week 8
Response to treatment defined by HAM-D total score decrease from baseline ≥ 50%	Depressive symptoms	at week 0, week 2, week 4, week 6 and week 8
Clinical Global Impression scale (CGI), item 1 (Severity of depression) and item 2 (global Improvement) scores, response to treatment (CGI item 2 = 1 or 2)	Depressive symptoms	CGI item 1 at week 0, week 2, week 4, week 6 and week 8 and item 2 at week 2, week 4, week 6 and week 8
Hospital Anxiety and Depression Scale (HAD), Anxiety and Depression sub-scores	Depressive symptoms	at week 0, week 2, week 4, week 6 and week 8
Sheehan Disability Scale (SDS) scores (Work, social and family life)	Social functioning	at week 0, week 2, week 4, week 6 and week 8
Adverse Events	Safety criterion	through study completion (an average of 12 weeks)
Body Weight	Safety criterion	at week 4 and week 8
BMI	Safety criterion	at week 4 and week 8
Laboratory tests (haematology and biochemistry)	Safety criterion	at week 4 and week 8
12-lead ECG	Safety criterion	at week 4 and week 8
Vital signs (standing and supine Systolic and Diastolic Blood Pressure, heart rate)	Safety criterion	at week 0, week 2, week 4, week 6 and week 8
Columbia-Suicide Severity Rating Scale (C-SSRS)	Safety criterion	at week 0, week 2, week 4, week 6 and week 8

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR Association

Publications and helpful links

Helpful Links

• Results summary

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimate): June 20, 2016

Study Record Updates

• Last Update Posted (Actual): January 3, 2020
• Last Update Submitted That Met QC Criteria: January 2, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CL2-47445-014; 2015-003867-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

• submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No