Proof-of-Concept Trial of CERC-501 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression

NCT01913535 | Terminated Phase 2 Results DMC

• 2 other identifiers: RAP-002271201100006I-0-27100007-1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Treatment Resistant Depression

Keywords

Depression; Treatment Resistant Depression; Antidepressant; Major Depression; MDD

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Rating Scale for Depression - 6 Items (HAM-D-6)

  This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. Scale items are assessed based on symptoms within the past 24 hours. A higher score indicates more depression symptoms. Total scores range from 0 (normal) to 22 (severe). To better estimate the baseline, we did not use simply the cross-sectional assessment at baseline, but we estimated the average during the screening period as the true baseline.

  Baseline and 72 hours after initiating treatment

Secondary Outcomes (12)

• Change in Hamilton Rating Scale for Depression - 6 Items (HAM-D-6), Day 20

  Baseline and 20 days after initiating treatment

• Number of Participants With Response on Hamilton Rating Scale for Depression - 6 Items (HAM-D-6)

  72 hours after treatment initiation

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  Baseline and 72 hours and 20 days after initiating treatment

• Change in Clinical Global Impression -Severity (CGI-S)

  Baseline and 72 hours and 20 days after initiating treatment

• Clinical Global Impression-Improvement (CGI-I)

  72 hours and 20 days after initiating treatment

Study Arms (5)

Low Dose Drug-Drug Arm

ACTIVE COMPARATOR

Patients in this arm will receive CERC-501 10.0 mg/day for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)

Drug: CERC-501

High Dose Drug-Drug Arm

ACTIVE COMPARATOR

Patients in this arm will receive CERC-501 20.0 mg/day for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)

Drug: CERC-501

Placebo/Low-Dose Drug Arm

OTHER

Patients in this arm will receive placebo for 3 days (in Phase 1) and CERC-501 10.0 mg/day for 3 days (in Phase 2)

Drug: CERC-501; Drug: Placebo

Placebo/High-Dose Drug Arm

OTHER

Patients in this arm will receive placebo for 3 days (in Phase 1) and CERC-501 20.0 mg/day for 3 days (in Phase 2)

Drug: CERC-501; Drug: Placebo

Placebo/Placebo Arm

PLACEBO COMPARATOR

Patients in this arm will receive placebo for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)

Drug: Placebo

Interventions

CERC-501 DRUG

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.

High Dose Drug-Drug Arm; Low Dose Drug-Drug Arm; Placebo/High-Dose Drug Arm; Placebo/Low-Dose Drug Arm

Placebo DRUG

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.

Placebo/High-Dose Drug Arm; Placebo/Low-Dose Drug Arm; Placebo/Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Mental Health (NIMH): collaborator
• Butler Hospital: collaborator
• Rush University: collaborator
• Temple University: collaborator
• University of Kansas: collaborator

Study Sites (4)

Rush University

Chicago, Illinois, United States

Location

University of Kansas

Wichita, Kansas, United States

Location

Temple University

Philadelphia, Pennsylvania, United States

Location

Brown University-Butler Hospital

Providence, Rhode Island, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Depressive Disorder, Major

Interventions

Aticaprant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Maurizio Fava, MD
• Organization: Massachusetts General Hospital

mfava@mgh.harvard.edu

617-724-2513

Study Officials

• Maurizio Fava, MD

  Massachusetts General Hospital (Coordinating Center)

  PRINCIPAL INVESTIGATOR

• Linda L Carpenter, MD

  Brown University-Butler Hospital

  PRINCIPAL INVESTIGATOR

• John Zajecka, MD

  Rush University

  PRINCIPAL INVESTIGATOR

• Mary F Morrison, MD

  Temple University

  PRINCIPAL INVESTIGATOR

• Matthew Macaluso, DO

  University of Kansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Overall Principal Investigator

Model Details: sequential parallel comparison design (SPCD) with two phases

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: September 12, 2013
• Primary Completion: January 22, 2016
• Study Completion: January 22, 2016
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-05

Locations

US (4)