Proof-of-Concept Trial of LY2456302 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
Brown University-Butler Hospital
Rush University
Temple University
University of Kansas
Wake Forest School of Medicine
Information provided by (Responsible Party):
Maurizio Fava, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01913535
First received: July 30, 2013
Last updated: NA
Last verified: July 2013
History: No changes posted
  Purpose

This study is looking at the efficacy, rapidity, safety, and tolerability of two doses of oral LY2456302 for treating patients with treatment resistant depression who are taking an antidepressant that is not working for them.


Condition Intervention Phase
Treatment Resistant Depression
Drug: LY2456302
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Double-Blind, Placebo-Controlled, Proof-of-Concept (POC) Trial of LY2456302, a Kappa-Selective Opioid Receptor Antagonist, Augmentation of Antidepressant Therapy in Treatment-Resistant Depression (TRD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Hamilton Rating Scale for Depression - 6 items [ Time Frame: Past 48 hours ] [ Designated as safety issue: No ]
    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. The time frame for this scale is the past 48 hours.


Estimated Enrollment: 91
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low Dose Drug-Drug Arm
Patients in this arm will receive LY2456302 10.0 mg/day for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)
Drug: LY2456302
Dose of LY2456302 will be 10 mg/day during the first phase (3 days) and during the second phase (3 days)
Active Comparator: High Dose Drug-Drug Arm
Patients in this arm will receive LY2456302 20.0 mg/day for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)
Drug: LY2456302
Dose of LY2456302 will be 20 mg/day during the first phase (3 days) and during the second phase (3 days)
Placebo/Low-Dose Drug Arm
Patients in this arm will receive placebo for 3 days (in Phase 1) and LY2456302 10.0 mg/day for 3 days (in Phase 2)
Drug: LY2456302
For patients randomly assigned to the placebo/low-dose drug sequence, the dose of LY2456302 will be 10 mg/day during the second phase of the study (3 days)
Placebo/High-Dose Drug Arm
Patients in this arm will receive placebo for 3 days (in Phase 1) and LY2456302 20.0 mg/day for 3 days (in Phase 2)
Drug: LY2456302
For patients randomly assigned to the placebo/high-dose drug sequence, the dose of LY2456302 will be 20 mg/day during the second phase of the study (3 days)
Placebo Comparator: Placebo/Placebo Arm
Patients in this arm will receive placebo for 3 days (in Phase 1) and for 3 subsequent days (in Phase 2)
Drug: Placebo
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)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 TRD 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 (Day -5/-14 and Day 0), 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 18-35 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01913535

Contacts
Contact: Maurizio Fava, MD 617-724-0838 mfava@partners.org
Contact: Martina Flynn 617-643-6028 mflynn2@partners.org

Locations
United States, Illinois
Rush University Not yet recruiting
Chicago, Illinois, United States
Principal Investigator: John Zajecka, MD         
United States, Kansas
University of Kansas Not yet recruiting
Wichita, Kansas, United States
Principal Investigator: Sheldon H Preskorn, MD         
United States, North Carolina
Wake Forest University Not yet recruiting
Winston-Salem, North Carolina, United States, 27157
Principal Investigator: James Kimball, MD         
United States, Pennsylvania
Temple University Not yet recruiting
Philadelphia, Pennsylvania, United States
Principal Investigator: Mary F Morrison, MD         
United States, Rhode Island
Brown University-Butler Hospital Not yet recruiting
Providence, Rhode Island, United States
Principal Investigator: Linda L Carpenter, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Brown University-Butler Hospital
Rush University
Temple University
University of Kansas
Wake Forest School of Medicine
Investigators
Principal Investigator: 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: Sheldon H Preskorn, MD University of Kansas
Principal Investigator: James Kimball, MD Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: Maurizio Fava, MD, Overall Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01913535     History of Changes
Other Study ID Numbers: RAP-003
Study First Received: July 30, 2013
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Depression
Treatment Resistant Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Central Nervous System Agents
Pharmacologic Actions
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014