Major depressive disorder MedDRA version: 20.0 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: rapastinel
Product Code: AGN-241659 (previously GLYX-13)
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: RAPASTINEL
Current Sponsor code: AGN-24165
Sponsors
Allergan Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Criteria to be assessed at Visit 1 (Screening) 1. Written informed consent, obtained from the patient before the initiation of any study-specific procedures 2. Male or female outpatients, 18 to 75 (inclusive) years of age at Visit 1 3. Meet DSM-5 criteria for MDD (based on confirmation from the MINI), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1 4. Have a minimum score of 26 on the rater-administered MADRS and a minimum score of 24 on the computer-administered MADRS at Visit 1 5. Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at Visit 1 6. Have a CGI-S score = 4 at Visit 1 7. Treatment naive in the present episode or have failed to respond ( 8 weeks during the present episode 8. Normal physical-examination findings, clinical-laboratory test results, and ECG results from Screening (Visit 1) or abnormal results that are determined to be not clinically significant by the investigator and documented as such in the eCRF 9. If female of childbearing potential, have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test at Visit 1 10. Ability to follow study instructions and likely to complete all required visits Criteria to be assessed at Visit 2 (Baseline) 11. Have a minimum score of 26 on the rater-administered MADRS and a minimum score of 24 on the computer-administered MADRS at Visit 2 12. Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at Visit 2 13. Have a CGI-S score = 4 at Visit 2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 620 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1. DSM-5–based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1. 2. Lifetime history of meeting DSM-5 criteria for: a. Schizophrenia spectrum or other psychotic disorder b. Bipolar or related disorder c. Major neurocognitive disorder d. Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the patient’s ability to consent, follow study directions, or otherwise safely participate in the study e. Dissociative disorder f. Posttraumatic stress disorder g. MDD with psychotic features 3. History of meeting DSM-5 criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Visit 1 4. DSM-5–based diagnosis of any personality disorder of sufficient severity to interfere with participation in this study in the opinion of the investigator 5. History of: a. Inadequate response to electroconvulsive therapy (ECT), a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic b. Treatment with clozapine or any depot antipsychotic c. ECT, vagus nerve stimulation, transcranial magnetic stimulation, or any experimental central nervous system treatment during the current episode or in the 6 months before Visit 1 (whichever is longer) d. Tardive dyskinesia, serotonin syndrome, or neuroleptic malignant syndrome e. Intolerance or hypersensitivity to rapastinel 6. Having received: a. Anticonvulsant/mood stabilizer, within 1 year prior to Visit 1 b. Antipsychotic in the current episode, with the exception of quetiapine given for insomnia = 50 mg/day provided it can be safely discontinued prior to Visit 2 c. Combination therapy of 2 or more ADTs in the current episode if given for depression at adequate dose and duration d. ADT augmentation agent in the current episode 7. Positive result at Visit 1 from the urine drug screen (UDS) test for any prohibited medication. Exception: patients with a positive UDS at Visit 1 for opiates, cannabinoids or episodic use of benzodiazepines may be allowed as described more detailed in the protocol 8. Suicide risk, as determined by meeting any of the following criteria: a. A suicide attempt within the past year b. Significant risk, as judged by the investigator, based on the psychiatric interview or information collected in the C-SSRS at Visit 1 or Visit 2 c. MADRS Item 10 score = 5 at Visit 1 or Visit 2 on the MADRS 9. At imminent risk of injuring self or others or causing significant damage to property, as judged by the investigator 10. Requiring concomitant treatment with any of the prohibited medications, supplements, or herbal products listed in Appendix III 11. Prior participation in any investigational study of rapastinel/GLYX-13 12. Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study 13. Ongoing treatment with phototherapy, or termination of phototherapy within 1 month of Visit 1 14. Weight 125 kg at screening 15. Females who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study 16. Females of childbearing potential and male partners of females of childbearing potential, not using a reliable means of contraception 17. Any cardiovascular disease that is clinically significant, unstable, or decompensated 18. Heart rate (supine) of = 45 bpm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as measured by the change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score at end of treatment (end of week 6);Secondary Objective: To evaluate the efficacy of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as measured by the change from baseline MADRS total score at 1 day post-first dose of treatment To evaluate the safety and tolerability of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as evaluated by adverse events (AEs), clinical laboratory measures, electrocardiograms (ECGs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS);Primary end point(s): Change from baseline in MADRS total score at the end of the double-blind treatment period (end of Week 6);Timepoint(s) of evaluation of this end point: After 6 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoint: Change from baseline in MADRS total score at 1 day after first dose of investigational product (IP) Other: • Change from baseline in MADRS at 7 days after first dose of treatment • Change from baseline in CGI-S at 1 and 7 days after first dose of treatment, and end of treatment • Rate of sustained responders during treatment • Rate of responders at 1 and 7 days after first dose of treatment, and end of treatment (end of Week 6) • Rate of sustained remitters during treatment • Rate of remitters at 1 and 7 days after first dose of treatment, and end of treatment (end of Week 6) • Time to first response • Time to first sustained response • Time to first remission • Time to first sustained remission • Change from baseline in Sheehan Disability Scale (SDS) at end of treatment ;Timepoint(s) of evaluation of this end point: Key secondary endpoint: Change from baseline in MADRS total score at 1 day after first dose of investigational product (IP) Additional endpoints: At each visit and the final analysis will be done at the end of the study | — |
Countries
Hungary, Japan, Poland, Russian Federation, Slovakia, Ukraine
Contacts
Public ContactEU Global Clinical Trial Management
Allergan Ltd.
Outcome results
None listed