Major Depressive Disorder
Conditions
Keywords
MDD
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.
Interventions
DRUGCX157 (TriRima)
Six capsules administered three times a day for six weeks.
DRUGPlacebo
Six capsules administered three times a day for six weeks.
Sponsors
CeNeRx BioPharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS) | Randomization and study end (Week 6). | The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD \[Montgomery, 1979\]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. MADRS was assessed at randomization and Weeks 1, 2, 4 and 6 of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate | Week 6 or the last available post treatment result (LOCF) | MADRS is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD \[Montgomery, 1979\]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. Percentage of participants who achieved a reduction in total MADRS score of at least 50% or more as compared to baseline. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Responder rate at Week 6 or the last available post treatment result (LOCF) is reported here. |
| Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate | Week 6 or the last available post treatment result (LOCF) | Percentage of participants with total MADRS score of 11 or less. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Remitter rate at Week 6 or the last available post treatment result (LOCF)is reported here. |
| Clinical Global Impression - Severity of Illness (CGI-S) | Week 6 or the last available post treatment result (LOCF) | CGI-S measures the study rater's assessment of the severity of depression illness. CGI-S is rated on a scale of 1-7 as follows: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill patients. CGI-S was measured at randomization and Weeks 1, 2, 4 and 6. Percentage of subjects reported as normal, not at all ill; borderline mentally ill; and mildly ill is reported here at Week 6 or the last available post treatment result (LOCF). |
| Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items) | Randomization and Week 6 or the last available post treatment result (LOCF) | IDSR-SR 30 measures the severity of depressive symptoms by subjects. This scale has 30 items. The minimum score is 0 and the maximum possible IDS-30 score is 90 (the highest severity). IDS-SR30 was administered at screening, randomization and Weeks 1, 2, 4, and 6. Change from randomization in the IDS-SR30 total score at Week 6 or the last available post treatment result (LOCF) is reported here. |
| Clinical Global Impression - Improvement of Illness (CGI-I) | Week 6 or the last available post treatment result (LOCF) | The Clinical Global Impression - Improvement of Illness (CGI-I) was rated on a 7-point scale by the investigator to measure subject's total improvement compared to his/her condition at randomization according to the following scale: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I was measured at Weeks 1, 2, 4 and 6. Percentage of participants very much improved and much improved at Week 6 or the last available post treatment result (LOCF) is reported here. |
| The Hospital Anxiety and Depression Scale (HADS) | Randomization and Week 6 or the last available post treatment result (LOCF) | HADS is a subject-rated questionnaire designed to detect states of anxiety and depression. The HADS consists of 14 questions relating to anxiety or depression, each with a choice of four responses \[Zigmond, 1983\]. These responses are numerically scored 0-3, with 0 representing the least severe response and 3 representing the most severe response. The highest possible total score is 42. HADS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. Change from randomization in the HADS total score at Week 6 or the last available post treatment result (LOCF) is reported here. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 14 out-patient medical centers in the United States (US) from 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit).
Pre-assignment details
A total of 587 subjects were screened. Three hundred and two (302) subjects failed to meet study entry criteria, and thus were screen failures. The top three reasons for screen failure were: IDS-SR30 total score cut-off for randomization not met (204 pts); presence of cardiovascular abnormality (18 pts) and Laboratory Abnormalities (14 pts).
Participants by arm
| Arm | Count |
|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI) | 142 |
| Oral Placebo TID Placebo does not have any active medication and is the same as a Sugar Pill. | 143 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 14 | 9 |
| Overall Study | Non-Compliance With Study Medication | 0 | 3 |
| Overall Study | Non-Compliance With Study Procedures | 2 | 3 |
| Overall Study | Relocation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Oral Placebo TID | Total | Oral CX157 60 mg TID (Total Daily Dose of 180 mg) |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 5 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 138 Participants | 280 Participants | 142 Participants |
| Age Continuous | 38.5 years STANDARD_DEVIATION 11.16 | 38.8 years STANDARD_DEVIATION 11.14 | 39.1 years STANDARD_DEVIATION 11.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 62 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 105 Participants | 207 Participants | 102 Participants |
| Region of Enrollment United States | 143 participants | 285 participants | 142 participants |
| Sex: Female, Male Female | 81 Participants | 161 Participants | 80 Participants |
| Sex: Female, Male Male | 62 Participants | 124 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 39 / 142 | 27 / 143 |
| serious Total, serious adverse events | 3 / 142 | 3 / 143 |
Outcome results
Primary
Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS)
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD \[Montgomery, 1979\]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. MADRS was assessed at randomization and Weeks 1, 2, 4 and 6 of the study.
Time frame: Randomization and study end (Week 6).
Population: mITT population consisted of all patients with at least one post randomzation MADRS score. The primary efficacy variable was the change-from-randomization to each available post-randomization measurement of the MADRS total score, used as the response variable in a mixed model repeated measures (MMRM) analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS) | -12.5 units on a scale |
| Oral Placebo TID | Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS) | -12.3 units on a scale |
Secondary
Clinical Global Impression - Improvement of Illness (CGI-I)
The Clinical Global Impression - Improvement of Illness (CGI-I) was rated on a 7-point scale by the investigator to measure subject's total improvement compared to his/her condition at randomization according to the following scale: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I was measured at Weeks 1, 2, 4 and 6. Percentage of participants very much improved and much improved at Week 6 or the last available post treatment result (LOCF) is reported here.
Time frame: Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomzation MADRS score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Clinical Global Impression - Improvement of Illness (CGI-I) | 36.7 Percentage of Participants |
| Oral Placebo TID | Clinical Global Impression - Improvement of Illness (CGI-I) | 39.9 Percentage of Participants |
Secondary
Clinical Global Impression - Severity of Illness (CGI-S)
CGI-S measures the study rater's assessment of the severity of depression illness. CGI-S is rated on a scale of 1-7 as follows: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill patients. CGI-S was measured at randomization and Weeks 1, 2, 4 and 6. Percentage of subjects reported as normal, not at all ill; borderline mentally ill; and mildly ill is reported here at Week 6 or the last available post treatment result (LOCF).
Time frame: Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomzation MADRS score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Clinical Global Impression - Severity of Illness (CGI-S) | 36.7 Percentage of Participants |
| Oral Placebo TID | Clinical Global Impression - Severity of Illness (CGI-S) | 39.9 Percentage of Participants |
Secondary
Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items)
IDSR-SR 30 measures the severity of depressive symptoms by subjects. This scale has 30 items. The minimum score is 0 and the maximum possible IDS-30 score is 90 (the highest severity). IDS-SR30 was administered at screening, randomization and Weeks 1, 2, 4, and 6. Change from randomization in the IDS-SR30 total score at Week 6 or the last available post treatment result (LOCF) is reported here.
Time frame: Randomization and Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomzation MADRS score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items) | -22.58 units on a scale |
| Oral Placebo TID | Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items) | -23.39 units on a scale |
Secondary
Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate
Percentage of participants with total MADRS score of 11 or less. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Remitter rate at Week 6 or the last available post treatment result (LOCF)is reported here.
Time frame: Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomzation MADRS score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate | 19.4 Percentage of Participants |
| Oral Placebo TID | Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate | 23.1 Percentage of Participants |
Secondary
Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate
MADRS is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD \[Montgomery, 1979\]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. Percentage of participants who achieved a reduction in total MADRS score of at least 50% or more as compared to baseline. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Responder rate at Week 6 or the last available post treatment result (LOCF) is reported here.
Time frame: Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomization MADRS score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate | 31.7 percentage of participants |
| Oral Placebo TID | Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate | 34.3 percentage of participants |
Secondary
The Hospital Anxiety and Depression Scale (HADS)
HADS is a subject-rated questionnaire designed to detect states of anxiety and depression. The HADS consists of 14 questions relating to anxiety or depression, each with a choice of four responses \[Zigmond, 1983\]. These responses are numerically scored 0-3, with 0 representing the least severe response and 3 representing the most severe response. The highest possible total score is 42. HADS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. Change from randomization in the HADS total score at Week 6 or the last available post treatment result (LOCF) is reported here.
Time frame: Randomization and Week 6 or the last available post treatment result (LOCF)
Population: mITT population consisted of all patients with at least one post randomzation MADRS score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Oral CX157 60 mg TID (Total Daily Dose of 180 mg) | The Hospital Anxiety and Depression Scale (HADS) | -8.7 units on a scale |
| Oral Placebo TID | The Hospital Anxiety and Depression Scale (HADS) | -8.9 units on a scale |