BTRX-246040 Administered Once Daily to Patients With Major Depressive Disorder

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy And Safety Study Of BTRX-246040 Administered Once Daily In Patients With Major Depressive Disorder With Or Without Anhedonia

This study will determine the efficacy, safety, and tolerability of a once-daily (QD) dose of up to 80 mg of BTRX-246040 for 8 weeks in participants with MDD.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: BTRX-246040 oral capsule(s); Drug: Placebo oral capsule(s)

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Cerritos, California, United States, 90703
      • United States
    • Garden Grove, California, United States, 92845
      • United States
  • Florida
    • Jacksonville, Florida, United States, 32256
      • United States, Florida
    • Lauderhill, Florida, United States, 33319
      • United States
    • Orlando, Florida, United States, 32801
      • United States, Florida
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • United States
  • New York
    • Rochester, New York, United States, 14618
      • United States
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • United States

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:

• Patients with a diagnosis of MDD as defined by DSM-5 criteria and have had at least 1 prior major depressive episode in the past 10 years
• Patients must present with a new current episode of MDD and the duration of the current episode must be at least 4 weeks but not longer than 18 months.
• At Visit 1 (screening) and Visit 2 (baseline), patients must have clinically significant depressive symptoms defined by tandem (investigator- and computer-administered) Montgomery-Asberg Depression Rating Scale (MADRS) total scores ≥ 26 with a difference of ≤ 7 points between the Investigator- and computer-administered MADRS total scores
• Patients must have a CGI-S score ≥ 4 at Visit 2 (baseline).

Exclusion Criteria:

• Patients who present with any current DSM-5 disorder other than MDD which is the focus of treatment.
• Patients who are homicidal in the opinion of the Investigator or are at suicidal risk (any suicide attempts within 12 months prior to Visit 1 [screening] or any suicidal intent, including a plan, within 3 months prior to Visit 1 [screening]; C-SSRS answer of "YES" on item 4 or 5 [suicidal ideation]; Investigator- or computer-administered MADRS score of ≥ 5 on item 10 [suicidal thoughts]; by Investigator clinical evaluation).
• Patients cannot have any history of substance or alcohol use disorder within 12 months prior to Visit 1 (screening) per DSM-5 criteria
• Patients must not have a clinically significant comorbid disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BTRX-246040; 40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks.	Drug: BTRX-246040 oral capsule(s); BTRX-246040 administered once daily to patients with MDD for 8 weeks
PLACEBO_COMPARATOR: Placebo; administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks.	Drug: Placebo oral capsule(s); administered once daily to patients with MDD for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo	The Investigator-administered MADRS includes 10 items assessing the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 60. MADRS total scores from 0 to 6 indicate normal/symptom absent, from 7 to 19 indicate mild depression, from 20 to 34 indicate moderate depression, and from 35 to 60 indicate severe depression.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Investigator-administered MADRS-6 Total Score	The Investigator-administered MADRS-6 subscale focuses on the core symptoms of depression and assesses the following symptoms: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36. The change from baseline in the Investigator-administered MADRS-6 subscale was analyzed using the same method as the MADRS efficacy endpoint, substituting the baseline MADRS-6 subscale as the covariate in place of the MADRS total score.	Week 8
Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score	The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.	Week 8
Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score	The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.	Week 8
Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS)	The Investigator-administered Dimensional Anhedonia Rating Scale (DARS) is a 17-item questionnaire with each answer between 0 and 4 on a Likert scale grading (0=Not at all, 1=Slightly, 2=Moderately, 3=Mostly, 4=Very Much). Therefore, the DARS total score is on a scale of 0 - 68. The DARS Total score is broken down into four dimensions; Hobbies, Food/Drink, Social Activities and Sensory Experience.	Week 8
Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score	The Investigator-administered Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item questionnaire. The SHAPS is scored two different ways. Under the original scoring method, each question has 4 responses, 2 of which imply agreement (Definitely Agree, Agree; each scored as 0) and 2 which imply disagreement (Disagree, Strongly Disagree; each scored as 1). Therefore, the SHAPS total score ranges 0 - 14. In this study, in addition to the traditional scoring method, an alternative scoring method will assign 1 - Strongly Agree, 2 - Agree, 3 - Disagree, and 4 - Strongly Disagree. Using this alternative scoring method, the total score ranges 14-56. In both scoring systems, higher scores indicate greater anhedonia.	Week 8

Collaborators and Investigators

• Sponsor: BlackThorn Therapeutics, Inc.
• Investigators: Study Director: Jane Tiller, MD, BlackThorn Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 12, 2017
• Primary Completion (ACTUAL): November 12, 2018
• Study Completion (ACTUAL): December 12, 2018

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (ACTUAL): June 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Anhedonia; antidepressant; Nociceptin; NOPR
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: NEP-MDD-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No