Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Rapastinel · 7 trials · 3 indications
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse.
On the C-SSRS, the 5 types of suicidal ideation are: Type 1: "Wish to be dead" Type 2: Non-specific active suicidal thoughts Type 3: "Active suicidal ideation with any methods (not plan) without intent to act" Type 4: "Active suicidal ideation with some intent to act, without specific plan" Type 5: "Active suicidal ideation with specific plan and intent"
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
The drug liking VAS measures the participant's liking for the drug and is scored from 0 to 100, with 0 reflecting "Strong disliking" and 100 reflecting "Strong liking".
| Arm | Type | Description |
|---|---|---|
| Rapastinel | EXPERIMENTAL | Rapastinel 450 milligrams (mg) intravenous (IV) open label weekly or every two weeks, based on investigator's discretion for 52 Weeks. |
| Rapastinel 450 mg Weekly | EXPERIMENTAL | Rapastinel 450 milligrams (mg) intravenous (IV) once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP. |
| Rapastinel 450 mg Every 2 Weeks | EXPERIMENTAL | Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks during DBTP. |
| Placebo | PLACEBO_COMPARATOR | Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP. |
| Rapastinel 450 mg | EXPERIMENTAL | Rapastinel 450 mg weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment. |
| Rapastinel 225 mg | EXPERIMENTAL | Rapastinel 225 milligram (mg) weekly intravenous (IV) injections. Each participant will continue to take the same dose of antidepressant therapy the participant was receiving prior to entering this study throughout treatment. |
| Rapastinel High Dose | EXPERIMENTAL | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Rapastinel Low Dose | EXPERIMENTAL | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Alprazolam | ACTIVE_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Ketamine | ACTIVE_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Placebo for Rapastinel | PLACEBO_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Placebo for Alprazolam | PLACEBO_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Placebo for Ketamine | PLACEBO_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Part 1, Cohort 1: Ketamine Low Dose | EXPERIMENTAL | Some participants will be administered a single IV dose of ketamine on Day 1. |
| Part 1, Cohort 1: Placebo | PLACEBO_COMPARATOR | Some participants will be administered a single IV dose of placebo on Day 1. |
| Part 1, Cohort 2: Ketamine Medium Dose | EXPERIMENTAL | Some participants will be administered a single IV dose of ketamine on Day 1. |
| Part 1, Cohort 2: Placebo | PLACEBO_COMPARATOR | Some participants will be administered a single IV dose of placebo on Day 1. |
| Part 1, Cohort 3 (Optional): Ketamine High Dose | EXPERIMENTAL | Optional: some participants will be administered a single IV dose of ketamine on Day 1. |
| Part 1, Cohort 3 (Optional): Placebo | PLACEBO_COMPARATOR | Optional: some participants will be administered a single IV dose of placebo on Day 1. |
| Part 2, Qualification Phase: Ketamine | EXPERIMENTAL | Participants will receive IV ketamine on Day 1 and placebo on Day 2 in a randomized crossover manner. |
| Part 2, Qualification Phase: Placebo | PLACEBO_COMPARATOR | Participants will receive IV ketamine on Day 2 and placebo on Day 1 in a randomized crossover manner. |
| Part 2, Treatment Phase: Rapastinel Low Dose | EXPERIMENTAL | Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. |
| Part 2, Treatment Phase: Rapastinel Medium Dose | EXPERIMENTAL | Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. |
| Part 2, Treatment Phase: Rapastinel High Dose | EXPERIMENTAL | Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. |
| Part 2, Treatment Phase: Ketamine | ACTIVE_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. |
| Part 2, Treatment Phase: Placebo | PLACEBO_COMPARATOR | Participants will be administered single IV doses of rapastinel, ketamine, and placebo in a randomized crossover manner. |
| Name | Type | Description |
|---|---|---|
| Rapastinel | DRUG | Rapastinel pre-filled syringes for IV injections. |
| Placebo-matching Rapastinel | DRUG | Placebo-matching rapastinel pre-filled syringes for weekly IV injections. |
| Placebo | DRUG | Placebo-matching rapastinel pre-filled syringes for weekly IV injections. |
| Alprazolam | DRUG | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Ketamine | DRUG | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Rapastinel Matched Placebo | DRUG | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Alprazolam Matched Placebo | DRUG | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
| Ketamine Matched Placebo | DRUG | Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. |
Inclusion Criteria: * Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD * Current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Screening * Have no more than partial response (\< 50% improvement) to ongoing t...
Rapastinel is an investigational small molecule being studied for major depressive disorder, where it has been evaluated as adjunctive therapy in Phase 3 trials. It has also been studied in Phase 1 trials for driving performance and human abuse potential. It is not approved and remains in clinical development.
Rapastinel targets NMDA receptor subunits, specifically GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3B, and GRIN2C. It acts as a partial agonist at these receptor subunits, a mechanism distinct from standard monoaminergic antidepressants. This glutamatergic approach was being investigated for rapid antidepressant effects in major depressive disorder.
Rapastinel is being developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie holds the development program for this investigational compound across its psychiatric indications.
Rapastinel is in Phase 3 clinical development. Five trials have been completed, including two Phase 3 studies in major depressive disorder, and no trials are currently active. The program includes a long-term safety study and a relapse prevention study, both completed.
Rapastinel has been studied in five completed trials. These include NCT03002077, a Phase 3 long-term safety study as adjunctive therapy in major depressive disorder, and NCT02951988, a Phase 3 relapse prevention study. Phase 1 trials NCT03814733 and NCT03799900 assessed driving performance and human abuse potential, respectively.