A study to assess the effectiveness and safety of Lumateperone as another treatment used together with the primary treatment in the Treatment of Patients with Major Depressive Disorder
Scientific Title of Study
A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients with Major Depressive Disorder
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ITI-007-501 Amendment 2, dated 20 Aug 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Bulgaria Czech Republic Hungary India Republic of Korea Slovakia United States of America
Sites of Study
No of Sites = 20
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Nakul Vanjari
Assured Care Plus Hospital
Assured Care Plus Hospital,
4th & 5th Floor, Star Plus Complex, Lam Road, Near Muktidham Temple, Opposite NMC Divisional Office, Nashik Road, Nashik 422101, Maharashtra
Nashik MAHARASHTRA
9819625217
nakulv1986@gmail.com
Dr Parikh Minakshi Nimesh
B. J. Medical College and Civil Hospital
B. J. Medical College and Civil Hospital, Ahmedabad – 380016, Gujarat Ahmadabad GUJARAT
9825718696
drminakshiparikh@gmail.com
Dr Ashok Goyal
Bhagwan Mahaveer Psychiatry and De-Addiction Centre
Bhagwan Mahaveer Psychiatry and De-Addiction Centre, A unit of Sardarmal Khandaka Memorial Hospital, Kalwar Road, Hathoj, Jaipur-302012, Rajasthan Jaipur RAJASTHAN
9828809333
ashokgoyaldr@yahoo.com
Dr Shailesh Pangaonkar
Central Institute of Behavioral Sciences
Central Institute of Behavioral Sciences, Srividya, 8, Nawab Layout, Tilak Nagar, Nagpur - 440010, Maharashtra Nagpur MAHARASHTRA
9423105228
Pangaonkar11@gmail.com
Dr Satheesh Rao
Centre for Psychiatric Research
Department of Psychiatry, K.S. Hegde Hospital, K.S. Hegde Medical Academy, Nitte (Deemed to be University)
K.S. Hegde Medical Sciences Complex, Deralakatte, Mangaluru- 575018, Karnataka
Dakshina Kannada KARNATAKA
9845085561
dr_satheeshrao@yahoo.com
Dr PN Suresh Kumar
Chethana Centre For Neuropsychiatric Rehabilitation
Chethana Centre For Neuropsychiatric Rehabilitation, Providence College Road, Malaparamba, Kozhikode, Kerala -673009 Kozhikode KERALA
9447218825
drpnsuresh@gmail.com
Dr Umesh Nagapurkar
Chopda Medicare & Research Centre Pvt. Ltd
Chopda Medicare & Research Centre Pvt. Ltd; Magnum Heart Institute, 3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005, Maharashtra Nashik MAHARASHTRA
9823146088
umeshanjali@gmail.com
Dr Ranjive Kumar
Dayanand Medical College
Dayanand Medical College and Hospital, Civil Lines, Tagore Nagar, Ludhiana, Punjab - 141001 Ludhiana PUNJAB
9872655006
ranjive@yahoo.com
Dr Venu Gopal Jhanwar
Deva Institute of Healthcare & Research Pvt. Ltd.
Deva Institute of Healthcare & Research Pvt. Ltd.,
B 27/70 MN, Durgakund,
Varanasi, Uttar Pradesh - 221005
Varanasi UTTAR PRADESH
9935571052
vgj.dihr@gmail.com
Dr Sandip Shah
GMERS Medical College & Hospital, Department of Psychiatry
K R Hospital attached to Mysore Medical College and Research Institute
K R Hospital attached to Mysore Medical College and Research Institute,
Department of Psychiatry, K R Hospital attached to Mysore Medical College and Research Institute, Irwin Road, Mysuru-570001, Karnataka
Mysore KARNATAKA
9451518612
drnarendrakumar@gmail.com
DR Keshava Pai
Kasturba Medical College Hospital
Kasturba Medical College Hospital, Attavar, Mangalore- 575001, Karnataka Dakshina Kannada KARNATAKA
9448105227
pai.keshava@manipal.edu
Dr Adarsh Tripathi
King George’s Medical University
Department of Psychiatry, King George’s Medical University, Lucknow - 226003, UP Lucknow UTTAR PRADESH
Route: Oral
Dose: Formulated Capsules (42 mg)
At Baseline (Visit 2), patients who continue to meet all eligibility criteria will be randomized to 1 of 2 treatment arms, lumateperone 42 mg or matching placebo
Duration: Screening Phase up to 2 weeks, a 6-week Double-blind Treatment Period, a 1-week Safety Follow-up Period
Comparator Agent
Lumateperone or Placebo
Double-blind Treatment Period (6 weeks) in which all patients will be randomized to receive placebo or lumateperone 42 mg/day in 1:1 ratio.
Duration: Screening Phase up to 2 weeks, a 6-week Double-blind Treatment Period, a 1-week Safety Follow-up Period
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Patients will be eligible for study participation if they meet the following
inclusion criteria:
1. Provides written informed consent
2. Male or female patients between the ages 18 and 65 years, inclusive
3. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor approved rater using the MINI and meets all of the following criteria:
a. The start of the current major depressive episode (MDE) is at least 8 weeks but not more than 18 months prior to Screening (Visit 1)
b. Has at least moderate severity of illness based on rater administered MADRS total score ≥ 24 at Screening (Visit 1) and at Baseline (Visit 2)
c. Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening (Visit 1) and at Baseline (Visit 2)
d. Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening (Visit 1) and at Baseline (Visit 2)
e. Has sufficient history and medical record confirmation verifying the ADT and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.
4. Currently having an inadequate response to ADT (less than 50% improvement) as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration:
a. citalopram/escitalopram
b. fluoxetine
c. paroxetine
d. sertraline
e. duloxetine
f. levomilnacipran/milnacipran (if locally approved for MDD)
g. venlafaxine/desvenlafaxine
h. bupropion
i. vilazodone
j. vortioxetine
ExclusionCriteria
Details
Patients who meet any of the following exclusion criteria will not be able to participate in the study:
1. Within the patient’s lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:
a. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder
b. Bipolar disorder
2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:
a. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD,
provided these symptoms do not require concurrent treatment
b. Eating disorder
c. Substance use disorders (excluding nicotine)
d. Personality disorder of sufficient severity to have a major impact on the patient’s psychiatric status;
e. Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;
3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening (Visit 1) and Baseline (Visit 2)
4. The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening (Visit 1) and Baseline (Visit 2)
5. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:
a. At Screening (Visit 1), the patient scores “yes†on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline (Visit 2), the patient scores “yes†on Suicidal Ideation Items 4 or 5 since the Screening Visit b. At Screening (Visit 1), the patient has had 1 or more suicide attempts within 2 years prior to Screening
c. At Screening (Visit 1) or Baseline (Visit 2), the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or
d. The patient is considered to be in imminent danger to him/herself or others.
6. The patient has a first MDE at age 60 years or older
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
• To evaluate the efficacy of lumateperone 42 mg administered once daily compared with placebo as adjunctive treatment to antidepressant therapy in patients with Major Depressive Disorder (MDD) who have an inadequate response to ongoing antidepressant therapy (ADT) as measured by change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score
From baseline to Day 43
Secondary Outcome
Outcome
TimePoints
• To evaluate the efficacy of lumateperone 42 mg administered once daily compared with placebo as adjunctive treatment to ADT in patients with MDD who have an inadequate response to ongoing ADT as measured by change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S).
From baseline to Day 43
Target Sample Size
Total Sample Size="470" Sample Size from India="132" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is an international, multicenter, randomized, double-blind, placebo controlled,
parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.
The study will be conducted in three periods
•Screening Period (up to 2 weeks) during which patient eligibility will be assessed
•Double-blind Treatment Period (6 weeks) in which all patients will be randomized to receive placebo or lumateperone 42 mg/day in 1:1 ratio.
Safety Follow-up Period (1 week) in which all patients will return to the clinic for a safety follow-up visit approximately one week after the last dose of study treatment