Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With 25 mg Daily and 50 mg Daily of REL-1017 in Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03051256
Recruitment Status : Completed
First Posted : February 13, 2017
Last Update Posted : August 13, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Relmada Therapeutics, Inc.

Brief Summary:
This a Phase 2a, multicenter, randomized, double-blind, placebo controlled 3 arm study to assess the safety and tolerability of multiple oral doses of REL-1017 25 mg and 50 mg as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder (MDD). The patients will be adults with MDD who are diagnosed with a current MDE who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication. This population will provide the opportunity to compare the safety and efficacy effects of treatment with an approved antidepressant in conjunction with REL-1017 versus the effects of an antidepressant alone. This study includes in-patient and out-patient periods.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Drug: REL-1017 Drug: Placebo Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Assess the Safety, Tolerability, PK Profile, and Symptom Response of a 7-Day Dosing With REL-1017 25 mg Daily and 50 mg Daily as Adjunctive Therapy in the Treatment of Patients Diagnosed With Major Depressive Disorder
Actual Study Start Date : May 11, 2018
Actual Primary Completion Date : July 29, 2019
Actual Study Completion Date : August 6, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Methadone

Arm Intervention/treatment
Experimental: REL-1017 25 mg
REL-1017 75 mg of powder in 100 mL of Ocean Spray® Diet Cranberry Juice daily on Day 1, 25 mg of powder in 100 mL Ocean Spray® Diet Cranberry Juice daily on Day 2-7.
Drug: REL-1017
REL-1017 will be administered as an oral solution. Patients will continue to take the same, stabilized antidepressant medication that they were taking at screening throughout the course of the study.
Other Name: d-Methadone

Experimental: REL-1017 50 mg
REL-1017 100 mg of powder in 100 mL of Ocean Spray® Diet Cranberry Juice daily on Day 1, 50 mg of powder in 100 mL Ocean Spray® Diet Cranberry Juice daily on Day 2-7.
Drug: REL-1017
REL-1017 will be administered as an oral solution. Patients will continue to take the same, stabilized antidepressant medication that they were taking at screening throughout the course of the study.
Other Name: d-Methadone

Placebo Comparator: Placebo
100 mL Ocean Spray® Diet Cranberry Juice will be administered as a single oral dose daily for 7 days.
Drug: Placebo
Placebo will be administered as an oral solution. Patients will continue to take the same, stabilized antidepressant medication that they were taking at screening throughout the course of the study.




Primary Outcome Measures :
  1. Incidence of treatment emergent adverse events (AEs) [Safety and Tolerability] [ Time Frame: 21 days ]
    Spontaneously reported or observed AEs will be recorded and reported throughout the study, and AEs will be elicited using a non-leading question at every visit from Screening through the Day 21 assessment.


Secondary Outcome Measures :
  1. ECG parameters [Safety] [ Time Frame: 14 days ]
    12-Lead ECGs will be performed and reported at Screening; at Check In (Day -1); Days 1 through 9; and at Day 14.

  2. Clinical laboratory tests [Safety] [ Time Frame: 14 Days ]
    Clinical laboratory tests (chemistry, hematology, and urinalysis) will be conducted and reported at Screening, Check In (Day -1), Day 7, and Day 14.

  3. Columbia Suicide Severity Rating Scale (C-SSRS [Safety and Tolerability] [ Time Frame: 14 Days ]
    The C-SSRS will be administered and reported at Screening and Check In (Day -1); and at Days 1, 2, 8, 9 and 14.

  4. The Montgomery-Asberg Depression Scale (MADRS) [Efficacy] [ Time Frame: 14 days ]
    The Montgomery-Asberg Depression Scale (MADRS) will be administered and reported on Days 1, 2, 4, 7 and 14.

  5. The Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) [Efficacy] [ Time Frame: 14 days ]
    The Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR) will be administered and reported on Days 1, 2, 4, 7 and 14.

  6. The Clinical Global Impressions of Severity (CGI-S) [Efficacy] [ Time Frame: 14 days ]
    The Clinical Global Impressions of Severity (CGI-S) will be administered and reported on Days 1, 2, 4, 7, and 14.

  7. Maximum observed plasma concentration (Cmax) [Pharmacokinetic] [ Time Frame: 14 days ]
    The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.

  8. Area under the plasma concentration-time curve from time zero until the dosing interval of 24 hours (AUCtau) [Pharmacokinetic] [ Time Frame: 14 days ]
    The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.

  9. Time to maximum observed plasma concentration (Tmax) [Pharmacokinetic] [ Time Frame: 14 days ]
    The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.

  10. Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) [Pharmacokinetic] [ Time Frame: 14 days ]
    The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.

  11. Apparent terminal elimination half-life (t½) [Pharmacokinetic] [ Time Frame: 14 days ]
    The pharmacokinetic parameters of REL-1017 25 mg and 50 mg will be evaluated on Day 1 through Day 7, Day 8, Day 9, and Day 14 where the data allow.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males between 18 and 65 years of age, inclusive; and females between 18 and 65 years of age, inclusive, who are >1 year postmenopausal.
  2. Diagnosed with recurrent MDD as defined by the Diagnostic and Statistical Manual, Fifth Edition (DSM-5), and confirmed by the Mini International Neuropsychiatric Interview, Version 7.0.2 (MINI).
  3. Diagnosed with a current MDE lasting 8 weeks to 36 months as defined by the DSM-5 and confirmed by the MINI.
  4. Treated with an adequate dosage of a SSRI, SNRI, or bupropion during the current MDE for at least 8 weeks prior to Screening with the same, adequate dosage for the last 4 weeks. Minimum adequate doses are defined in the (ATRQ). The maximum dose allowed for paroxetine is 40 mg QD, for fluoxetine is 60 mg QD, and for sertraline is 200 mg QD.
  5. Have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication in the current episode, as defined as <50% improvement with an antidepressant medication at doses listed on the SAFER Interview Criteria: State versus trait; Assessability; Face validity; Ecological validity; and Rule of three Ps (pervasive, persistent, and pathological).
  6. Hamilton Depression Rating Scale-17 (HAM-D-17) ≥19 at Screening and Check-in (Day -1).
  7. BMI between 18.0 and 35.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
  8. Per the Investigator's judgment, able to meet all study requirements, including the confined/inpatient portion of the study, adherence with both approved ADT and study drug regimen, and completion of all assessments and all scheduled visits.
  9. Male patients of reproductive potential must be using and willing to continue using medically acceptable contraception, from Screening and for at least 2 months after the last study drug administration.
  10. Must be able to read, speak, and understand English and must provide written informed consent prior to the initiation of any protocol-specific procedures.

Exclusion Criteria:

  1. History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the patient or the validity of the study results, including torsades de pointes, any bradyarrhythmias, or uncompensated heart failure.
  2. Chronic use of prescribed opioids (i.e., >120 days in a 6-month period) up to 6 months prior to Screening or any recreational use of opioids.
  3. Evidence of clinically significant hepatic or renal impairment, including ALT or AST >1.5 x upper limit of normal (ULN), bilirubin >1 x ULN, or endocrine laboratory values (including clinically significant thyroid parameters, i.e., thyroid stimulating hormone [TSH], triiodothyronine [T3], and thyroxine [T4]).
  4. History or family history of sudden unexplained death or long QT syndrome (measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle).
  5. Any 12-lead ECG with repeated demonstration of QTc ≥450 msec or a QRS interval >120 msec at Screening.
  6. History of clinically diagnosed hypotension requiring treatment.
  7. History or presence of any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, bronchitis, or has/is suspected of having paralytic ileus).
  8. No more than 3 prescribed doses of an opioid within the 6 months prior to Screening and no use at all within the last month.
  9. Use of an antipsychotic, anticonvulsant, or mood stabilizer, regardless of indication, within the 3 months prior to Screening.
  10. History of allergy or hypersensitivity to methadone or related drugs (e.g., opioids).
  11. Positive test for hepatitis B or HIV. Patients with a positive hepatitis C test may be considered for inclusion with approval from the Medical Monitor.
  12. Any current and primary psychiatric disorder, as defined as a condition that is the primary focus of distress and/or treatment, other than MDD.
  13. Any lifetime history of bipolar I or II disorder, any psychotic disorder, post-traumatic stress disorder, borderline personality disorder, antisocial personality disorder, obsessive compulsive disorder, eating disorder, intellectual disability, or pervasive developmental disorder.
  14. History in the past 12 months of a primary diagnosis of anxiety disorder or panic disorder not related to the current MDE.
  15. Current diagnosis of alcohol or substance use disorder, as defined by DSM-5, at Screening or within the 12 months prior to Screening. Patients with the following diagnoses within the past 12 months, however, may be included at the Investigator's discretion: mild alcohol use disorder, mild cannabis use disorder, and any severity tobacco use disorder.
  16. A confirmed positive result on the urine drug/alcohol screen at Screening or Check-in. If the urine drug/alcohol screen is positive at Screening, retesting or rescreening may be scheduled with prior approval from the Medical Monitor.
  17. Patients who, in the Investigator's judgment, are at significant risk for suicide. A patient with a Columbia-Suicide Severity Rating Scale (C-SSRS) ideation score of 4 or 5 within the last 6 months or any suicide attempt within the past year must be excluded, as should a patient with an ideation score of 4 or 5 or any suicide attempt at the Check-in or Baseline Visit.
  18. Patients with a 20% improvement between Screening and Check-in (Day -1) on the HAM-D-17.
  19. Patients who did not safely discontinue medications prohibited.
  20. Patients receiving new onset psychotherapy (individual, group, marriage, or family therapy) within 2 months prior to Screening or plans to start at any time during participation in the study.
  21. Patients who have received electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or vagus nerve stimulation (VNS) or who have participated in a ketamine study within the last 6 months.
  22. Patients with any clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, chronic pain, or gastrointestinal disorder. Medical conditions that are minor or well-controlled may be permitted if they will not increase the safety risk to the patient or compromise interpretation of the safety or efficacy endpoints.
  23. Patients taking fluvoxamine or St. John's Wort.
  24. Patients who have participated in a clinical study with an investigational medication in the past 6 months, or who have participated in more than 4 clinical studies with investigational medications in the past 2 years.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03051256


Locations
Layout table for location information
United States, Arkansas
Woodland International Research Group
Little Rock, Arkansas, United States, 72211
United States, California
Collaborative Neuroscience Network, LLC
Garden Grove, California, United States, 92845-2506
Artemis Institute for Clinical Research
San Diego, California, United States, 92103
United States, Florida
Innovative Clinical Research, Inc
Hialeah, Florida, United States, 33012
United States, Georgia
Atlanta Center for Medical Research
Atlanta, Georgia, United States, 30331
iResearch Atlanta, LLC
Decatur, Georgia, United States, 30030
United States, Missouri
St. Louis Clinical Trials, LLC
Saint Louis, Missouri, United States, 63141
United States, New Jersey
Hassman Research Institute
Berlin, New Jersey, United States, 08009
United States, Ohio
Midwest Clinical Research Center
Dayton, Ohio, United States, 45417-3445
United States, Texas
Pillar Clinical Research, LLC
Richardson, Texas, United States, 75080
Sponsors and Collaborators
Relmada Therapeutics, Inc.
Syneos Health
Layout table for additonal information
Responsible Party: Relmada Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03051256    
Other Study ID Numbers: REL-1017-202
First Posted: February 13, 2017    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Relmada Therapeutics, Inc.:
REL-1017
d-Methadone
Methadone
Depression
Refractory Depression
Antidepressant
Adjunctive Treatment
NMDA Receptor Antagonist
Excitatory Amino Acid Antagonist
Glutamate Antagonist
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Methadone
D-methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents
Analgesics, Non-Narcotic