Repeated Intranasal Esketamine Plus Almond Therapy in Participants With Treatment Resistant Depressive Disorder - 3 Month Extension Study (ZYL-730-02)

Phase 2, Controlled, Single-Blind, 3-Month Extension Study For Participants Originally Diagnosed With Treatment Resistant Major Depressive Disorder (TRD) Who Complete Study ZYL-730-01 With, or Without, Almond Therapy

The purpose of this study is to determine if any improvements in depressive symptoms are maintained in the medium and longer-term (up to 3 months)

Study Overview

• Status: Withdrawn
• Conditions: Treatment Resistant Major Depressive Disorder
• Intervention / Treatment: Behavioral: Almond Therapy; Drug: Intranasal ketamine (Esketamine); Behavioral: Treatment as Usual

Detailed Description

The duration of the study is 3 months

Participants enrolled in the Almond Therapy group will have up to 9 in person visits, including the baseline visits, participants will receive Esketamine on 8 of these visits. There are 12 remote therapy sessions conducted via telephone or video, participants will also receive supportive text messages. In addition, participants will have 4 telephone calls from an independent assessor to ask questions about their mental health (MADRS).

Participants enrolled in the Treatment as Usual group will have up to 9 in person visits, including the baseline visits, participants will receive Esketamine on 8 of these visits. Participants will continue to receive the therapy their treating physician felt was appropriate at the time of enrolment in the study. In addition, participants will have 4 telephone calls from an independent assessor to ask questions about their mental health (MADRS).

Participants will receive intranasal Esketamine 56mg or 84 mg once weekly for 4 weeks and 56 mg or 84 mg once every 2 weeks for 8 weeks as per Product Monograph

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must have completed Study ZYL-730-01 through to Day 28
2. Adults aged 18-64
3. Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent.
4. Women must use a medically acceptable reliable means of contraception and must agree to use adequate birth control for the duration of the study and for 6 weeks after the last dose using methods from the permitted list for contraception.
5. If currently receiving medication for depression their antidepressant dose(s) must be stable for the previous 4 weeks prior to baseline.
6. Must be on a stable dose of all other medication(s) for at least 1-month prior to baseline visit., unless medication is to treat other short term conditions (i.e. influenza, upper respiratory track infections, pain, etc.)
7. Controlled hypertension and must be on a stable dose of antihypertensive medications for at least 3 months prior to the baseline visit.

Exclusion Criteria:

1. Women who plan to become pregnant, are pregnant or are breastfeeding.
2. Serious unstable medical illness, or any significant change in medical status at the baseline visit and during the study, as determined by the Investigator
3. Hormonal treatment (e.g., Estrogen) started within the 3 months prior to first dose of study treatment.
4. Participants who report treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) at the baseline visit and within 2 weeks prior to the first dose of Esketamine .
5. Participants with confirmed psychotic disorder or symptoms, bipolar disorder and or clinically significant alcohol or substance misuse confirmed by a psychiatrist at the baseline visit. Those participants who develop symptoms of these may be withdrawn from the study, as determined by the Investigator
6. Current diagnosis of bulimia nervosa, or development of significant eating disorder symptoms at the baseline visit or during the study as determined by the Investigator
7. Participants who have been diagnosed with ADD/ADHD and who are also currently taking stimulant medication such as methylphenidate or another amphetamine-type medication, or who are diagnosed with this disorder or who start medication for this during the study.
8. Participants currently taking St John's Wort, Ginseng or Turmeric who start any of these during the study
9. Participants judged clinically to be actively at serious risk of self-harm or suicidal behaviour by the study team or psychiatrist at baseline or at any time during the study, as determined by the Investigator.
10. Blood pressure >140/90 at baseline
11. Participants who are unable to easily travel to the clinic for all of the in-person visits.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intranasal Esketamine with Addition of Almond TherapyTM; Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.	Behavioral: Almond Therapy; Participants will receive 12 remote session conducted by video or phone. Therapy sessions consist of modules selected using a shared decision making process, tailored so that it is personally meaningful to each participants. Participants will also receive supportive text messages on selective days over the 3 months.; Drug: Intranasal ketamine (Esketamine); Participants will receive 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks
Other: Intranasal Esketamine with Treatment as Usual; Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.	Drug: Intranasal ketamine (Esketamine); Participants will receive 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks; Behavioral: Treatment as Usual; Participants will continue to received the therapy that their treating physician felt was appropriate at the time of enrolment in the study. These can include cognitive behavioural therapy, supportive psychotherapy or mindfulness, support groups, physical activity or relaxation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery Asberg Depression Rating Scale (MADRS)	The MADRS is a clinician rated 10-item scale where individuals score from 0-6 based on the severity of their symptoms with higher scores indicative of greater severity	Baseline, Day 26, 54 and 89

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders (PCL-5	A 20-item self-administered measure that assesses the presence and severity of PTSD symptoms derived from the symptoms of PTSD in DSM-5. Participants will be asked to rate how bothered they have been by each item in the 4 weeks on a 5-point Likert scale ranging from (0=Not at all to 4=Extremely). The PCL-5 is easily scored by summing all of the items for a total symptom severity score ranging between 0-80. Clinically meaningful PTSD symptoms are present if items are rated as a minimum of 2 = "Moderate" or higher.	Baseline, Day 26, 54 and 82
Change in Patient Health Questionnaire (PHQ-9)	A 9-item self-administered questionnaire to determine the presence and severity of depression which scores each of the 9 DSM-IV criteria as "0"(not at all), to "3" (nearly everyday	Baseline, Day 12, 26, 40, 54, 68 and 82
Change in Generalized Anxiety Disorder Questionnaire (GAD-7)	A 7-item self-administered questionnaire to measure the severity of the levels of anxiety. Each item can be scored 0-3, giving a total score of 0-21.	Baseline, Day 12, 26, 40, 54, 68 and 82
Change in Rosenberg Self-Esteem Questionnaire (RSES)	A 10-item self administered questionnaire to measure change in self esteem following psychological intervention. Each item scoring from 1-4, and higher scores indication greater self-esteem	Baseline, Day 26, 54 and 82
Change in Quality of Life 8 Dimensional Questionnaire (AQoL-8D)	Self administered questionnaire measuring quality of life across 8 domains: independent living, happiness, mental health, coping, relationships, self-worth, pain and senses	Baseline, Day 26, 54 and 82

Collaborators and Investigators

• Sponsor: Zylorion Health
• Investigators: Principal Investigator: Pierre Chue, MBBCh, Amygdala Associates Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2023
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: June 24, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: HREBA-CTC-22-0066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD will be available to other members of the study team including Dr. Craig Buchholz
• IPD Sharing Time Frame: Throughout the study
• IPD Sharing Access Criteria: Involved in data collection
• 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