Clinical trial NCT00739908: A Study of CX157 (TriRima) for the Treatment of Depression
Official title: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group, Assessment of the Efficacy, Safety and Tolerability of CX157 (TriRima) 60mg Three Times a Day (TID) in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: MDD
Lead sponsor: CeNeRx BioPharma Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-22
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the efficacy of CX157 60 mg administered three times a day (180 mg daily dose) as compared to placebo in subjects with Major Depressive Disorder (MDD). Secondary objectives are to evaluate the safety and tolerability and steady state pharmacokinetic profile of CX157 in these subjects.

Detailed description: This is a Phase II, randomized, double-blind, placebo-controlled, parallel-group, multi-center study comparing the efficacy, safety and tolerability of CX157 60mg TID and placebo. This study will be conducted at approximately 12 investigative sites in the US.

Subjects with suspected Major Depressive Disorder (MDD) and experiencing a Major Depressive Episode (MDE) who the investigator wishes to consider for enrollment in the study and who provide written informed consent will initially be evaluated by the Inventory of Depressive Symptomatology 30 item -Self Report (IDS-SR30) administered via Interactive Voice Response System (IVRS). Subjects who meet the minimum score of 40 on the IDS-SR30 will proceed with the remaining study related assessments at the Screening visit. Those subjects who meet all inclusion criteria and none of the exclusion criteria will enter a one to two week Screening period to confirm eligibility and to capture Screening data prior to Randomization. At the Randomization visit, all eligibility requirements will be reconfirmed. The subjects who meet all criteria will be randomized to study medication and enter into a six-week treatment period and a subsequent one week Follow-Up period. The total duration of participation for subjects who complete all phases of the study will be approximately 8-9 weeks. During the treatment period, clinic visits will occur at Week 1, Week 2, Week 4, and Week 6. A subsequent clinic visit will occur at the end of the one week Follow-Up period. The clinical site will contact the subjects via telephone at Weeks 3 and 5 to inquire about their wellbeing, query about adverse events and administer the suicidality scale.

Eligible subjects will be randomized (1:1) to receive:

* CX157 60mg three times a day (TID) for a total daily dose of 180 mg, or
* Placebo administered three times a day.

Subjects who discontinue from the study for any reason will not be replaced.

Eligibility criteria: Inclusion Criteria:

* Male or female = 18 years of age and \<60 years
* Able to read, understand, converse in English
* Willing to comply with diet restrictions, concomitant medication restrictions, \& all study requirements
* Good general health as ascertained by:Medical history, Physical exam, Supine \& standing vital signs, Clinical lab evaluations, 12-lead Electrocardiogram (ECG)
* Diagnosis of MDD;
* A total score =\>40 on the IDS-SR30 assessed via IVRS at Screening and Randomization

Exclusion Criteria:

* Subject's current MDD episode is \>2 years
* History of Substance Use Disorder at Screening or 12 months prior (except for nicotine)
* Current diagnosis of Obsessive-Compulsive Disorder;

  * Panic Disorder or Post-Traumatic Stress Disorder;
  * Anorexia nervosa, Bulimia nervosa, or eating disorder not otherwise specified;
  * Any Axis I Disorder clinically predominant to their MDD (within 6 mo);
  * Presence of psychotic features with current depressive episode;
  * Antisocial or Borderline Personality Disorder
* At risk for suicide
* Lack of response to \>2 trials of adequate dose \& duration of antidepressants of different mechanistic classes
* Electroconvulsive therapy within 1 year of Screening
* Subject has taken any psychoactive drug within 2 weeks of Randomization
* History of cardiac abnormalities including abnormal vital sign measurements
* Clinically significant abnormal ECG at Screening
* History within past 2 years of: Significant head trauma;

  * Surgical procedure involving brain or meninges; Encephalitis or meningitis;
  * Degenerative CNS disorder (Alzheimer's or Parkinson's);
  * Epilepsy;
  * Mental retardation
* Clinically significant Liver Function Test (LFT) and other lab abnormalities
* A history of hypothyroidism and treatment with a stable dosage of thyroid replacement medication for \<6 months prior to Screening
* A history of hyperthyroidism treated (medically or surgically) \<6 months prior to Screening
* Participation in a clinical investigation of a psychotropic drug within 90 days prior to Screening OR used any other investigational drug within 60 days prior to Screening
* Presence of any medical history which includes:

  * Hypersensitivity to CX157 or excipients, other MAO inhibitors, or other phenylethylamines;
  * Diabetes mellitus Type I, uncontrolled Type II, or controlled Type II managed with insulin; Malignancy/chemotherapy within 2 years prior to Screening;
  * Malignancy \>2 yrs may not preclude participation if the malignancy was local and without metastasis or recurrence and, if treated with chemotherapy, had no nervous system complications (e.g basal cell carcinoma);
  * Pheochromocytoma
* Positive urine test for drugs of abuse (blood for alcohol)
* Female subject who is pregnant or lactating
* Poor likelihood of subject's cooperation or compliance

Primary outcomes:
measure: Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS)
timeFrame: Randomization and study end (Week 6).
Secondary outcomes:
measure: Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate
timeFrame: Week 6 or the last available post treatment result (LOCF)
measure: Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate
timeFrame: Week 6 or the last available post treatment result (LOCF)
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: Randomization and Week 6 or the last available post treatment result (LOCF)
measure: Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items)
timeFrame: Randomization and Week 6 or the last available post treatment result (LOCF)
measure: Clinical Global Impression - Improvement of Illness (CGI-I)
timeFrame: Week 6 or the last available post treatment result (LOCF)
measure: Clinical Global Impression - Severity of Illness (CGI-S)
timeFrame: Week 6 or the last available post treatment result (LOCF)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Research Group
state: Alabama
city: Beverly Hills
country: United States
facility: Southwestern Research, Inc.
state: California
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Winter Park
country: United States
facility: Irving S. Kolin, M.D.
state: Florida
city: Oakbrook Terrace
country: United States
facility: Midwest Center for Neurobehavioral Medicine
state: Illinois
city: Rockville
country: United States
facility: Capital Clinical Research Associates
state: Maryland
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Clementon
country: United States
facility: CRI Worldwide, LLC
state: New Jersey
city: New York
country: United States
facility: Fieve Clinical Services
state: New York
city: Raleigh
country: United States
facility: Richard H. Weisler, M.D., P.A.
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Austin
country: United States
facility: FutureSearch Trials
state: Texas
city: Seattle
country: United States
facility: Summit Research Network (Seattle), LLC
state: Washington
city: Brown Deer
country: United States
facility: Northbrooke Research Center
state: Wisconsin
Study officials:
affiliation: CeNeRx BioPharma Inc.
name: Daniel Burch, MD
role: STUDY_DIRECTOR
References:
citation: Targum SD. Early symptomatic improvement affects treatment outcome in a study of major depressive disorder. J Psychiatr Res. 2017 Dec;95:276-281. doi: 10.1016/j.jpsychires.2017.09.009. Epub 2017 Sep 8.