Proof-of-Concept Trial of CERC-501 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression
Condition: Treatment Resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: CERC-501; Placebo
Intervention description: Low dose of CERC-501 will be 10 mg/day during the first phase (3 days) and during the second phase (3 days).
High Dose of CERC-501 will be 20 mg/day during the first phase (3 days) and during the second phase (3 days).
For patients randomly assigned to the placebo/low-dose drug sequence, the patient will receive placebo for 3 days and then 10 mg/day CERC-501 for the following 3 days.
For patients randomly assigned to the placebo/high-dose drug sequence, the patient will receive placebo for 3 days and then 20 mg/day CERC-501 for the following 3 days.; For patients randomly assigned to the placebo/ placebo sequence, study medication will be placebo during the first phase (3 days) and during the second phase (3 days).
For patients randomly assigned to the placebo/low-dose drug sequence, the patient will receive placebo for 3 days and then 10 mg/day CERC-501 for the following 3 days.
For patients randomly assigned to the placebo/high-dose drug sequence, the patient will receive placebo for 3 days and then 20 mg/day CERC-501 for the following 3 days.
Intervention MeSH terms: Aticaprant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: sequential parallel comparison design (SPCD) with two phases
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Depression; Treatment Resistant Depression; Antidepressant; Major Depression; MDD

Summary:

      This study is looking at the efficacy, rapidity, safety, and tolerability of two doses of
      oral CERC-501 for treating patients with treatment resistant depression who are taking an
      antidepressant that is not working for them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18-65 years old.

          -  Able to read, understand, and provide written, dated informed consent prior to
             screening.

          -  Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently
             experiencing a Major Depressive Episode (MDE) of at least eight weeks in duration,
             prior to screening.

          -  Has a history of treatment resistance during the current MDE.

          -  Meet the threshold on the total MADRS score of greater than or equal to 20 at both
             screening and baseline visits, as confirmed by the remote centralized MGH CTNI rater
             between the screen visit and the baseline visit.

          -  In good general health

          -  For female participants, status of non-childbearing potential or use of an acceptable
             form of birth control

          -  Body mass index between 18-40 kg/m2

          -  Concurrent psychotherapy will be allowed if the type and frequency of the therapy has
             been stable for at least three months prior to screening and is expected to remain
             stable during participation in the study

          -  Concurrent benzodiazepine and hypnotic therapy will be allowed if the therapy has been
             stable for at least 4 weeks prior to screening and if it is expected to remain stable
             during the course of the subject's participation in the study.

        Exclusion Criteria:

          -  Female of childbearing potential who is not willing to use one of the specified forms
             of birth control during the study

          -  Female that is pregnant or breastfeeding

          -  Female with a positive pregnancy test at screening or baseline

          -  History during the current MDE of failure to achieve a satisfactory response to >3
             treatment courses of a therapeutic dose of an antidepressant therapy of at least 8
             weeks duration during the current episode

          -  Total MADRS score of <20 at the screen or baseline visits, or as assessed by the
             remote, independent MGH CTNI rater and reported to the site

          -  Current diagnosis of a Substance Use Disorder (Abuse or Dependence) with the exception
             of nicotine dependence, at screening or within six months prior to screening

          -  Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized
             Anxiety Disorder, Social Anxiety Disorder, Panic Disorder or Specific Phobia (unless
             one of these is comorbid and clinically unstable, and/or the focus of the
             participant's treatment for the past 6 months or more)

          -  History of bipolar disorder, schizophrenia or schizoaffective disorders, or any
             history of psychotic symptoms in the current or previous depressive episodes

          -  History of eating disorders within five years of screening

          -  Any Axis I or Axis II Disorder, which at screening is clinically predominant to their
             MDD or has been predominant at any time within 6 months prior to screening

          -  Subject is considered at significant risk for suicidal behavior during the course of
             their participation in the study

          -  Subject has had electroconvulsive therapy in the current episode of depression

          -  Has received vagus nerve stimulation (VNS) at any time prior to screening

          -  Dementia, delirium, amnestic, or any other cognitive disorder

          -  Has a clinically significant abnormality on the screening physical examination

          -  Participation in any clinical trial with an investigational drug or device within the
             past month or concurrent to study participation

          -  Known history or current episode of: Uncontrolled hypertension, Recent myocardial
             infarction (within one year) or a history of more than one myocardial infarction,
             Syncopal event within the past year, Congestive heart failure, Angina pectoris,
             Systolic BP <85 or >160 mmHg or diastolic BP >95 mmHg or heart rate <50 or >105 beats
             per minute at screening or randomization, or QTcF greater than or equal to 450 msec at
             screening or randomization.

          -  Chronic lung disease

          -  Lifetime history of surgical procedures involving the brain or meninges, encephalitis,
             meningitis, degenerative central nervous system disorder, epilepsy, mental
             retardation, or any other disease/procedure/accident/intervention associated with
             significant injury to or malfunction of the central nervous system, or a history of
             significant head trauma within the past 2 years

          -  Presents with a history of Thyroid stimulating hormone outside of the normal limits
             and clinically significant as determined by the investigator

          -  Patients with diabetes mellitus fulfilling any of the following criteria:

               1. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at
                  screening

               2. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus
                  related illness in the past 12 weeks

               3. Not under physician care for diabetes mellitus

               4. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4
                  weeks prior to screening. For thiazolidinediones (glitazones) this period should
                  not be less than 8 weeks.

               5. Any other clinically significant abnormal laboratory result (as determined after
                  evaluation by study investigator and MGH CTNI medical monitor) at the time of the
                  screening exam.

          -  History of hypothyroidism and has been on a stable dosage of thyroid replacement
             medication, or was surgically treated less than six months prior to screening

          -  History of hyperthyroidism which was treated (medically or surgically) less than six
             months prior to screening

          -  Any current or past history of any physical condition which in the investigator's
             opinion might put the subject at risk or interfere with the interpretation of study
             results

          -  History of positive screening urine test for drugs of abuse

          -  Patients with exclusionary laboratory values, or requiring treatment with exclusionary
             concomitant medications, including tricyclic antidepressants and monoamine oxidase
             inhibitors, or on two or more concomitant antidepressant therapies

          -  Patients currently taking a proton pump inhibitor (PPI)/histamine 2 (H2) blocker or
             with a history of chronic NSAID use

          -  Patients with a positive test for Helicobacter pylori (urea breath test)

          -  Patients with any of the following GI-related findings:

               1. Clinically evident GI complaints or GI disease at Screening or Visit 1

               2. Past history of gastric disease (including but not limited to peptic ulcer
                  disease, gastritis (including atrophic gastritis), upper GI bleeding, any other
                  GI precancerous conditions), and of any other clinically relevant GI disease.