Small Molecule · OPC-64005
OPC-64005
An orally administered serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), also termed a triple reuptake inhibitor (TRI), synthesized and developed by Otsuka Pharmaceutical. It inhibits reuptake at the serotonin (SERT), norepinephrine (NET), and dopamine (DAT) transporters, increasing extracellular monoamine concentrations. Developed for major depressive disorder; a Phase 2 MDD trial in Japan completed in 2022 and missed its primary MADRS endpoint. Also reached Phase 2 in adult ADHD (trial met its primary endpoint) before ADHD development was discontinued. The compound's chemical structure has not been publicly disclosed, so no public chemical-database identifiers are available.
Also known as: OPC-64005
- Modality
- Small molecule
- Mechanism
- SERT Reuptake inhibitor
- Highest phase
- Discontinued
- Lead indication
- Major depressive disorder
- Developer
- Otsuka Pharmaceutical Co., Ltd. (4578.T)
- Trials
- 2 tracked · 27 sites
Mechanism of action
Triple monoamine reuptake inhibitor (serotonin-norepinephrine-dopamine reuptake inhibitor; SNDRI / TRI). Nonclinical studies report inhibition of reuptake at the serotonin (SERT/SLC6A4), norepinephrine (NET/SLC6A2), and dopamine (DAT/SLC6A3) transporters, increasing extracellular 5-HT, NE, and DA in the rat medial prefrontal cortex and extracellular DA in the striatum. Published human/clean affinity constants (Ki/IC50) for the three transporters are not available, so affinity values are left null.
| Target | Action | Affinity |
|---|---|---|
| SERTprimarySLC6A4 | Reuptake inhibitor | —ⓘ |
| DATSLC6A3 | Reuptake inhibitor | —ⓘ |
| NETSLC6A2 | Reuptake inhibitor | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| OPC-64005 oral tablet 10 mg or 20 mg once daily (20 mg reached via 1-week titration from 10 mg); studied in the Phase 2 MDD trial NCT04244253 | Oral | Once daily | Tmax 3 h |
Development timeline
- missedOPC-64005 Phase 2 MDD trial (NCT04244253, Japan, n=273) missed its primary MADRS endpoint at Week 6 (20 mg vs placebo p=0.288).
- Phase 2 MDD trial NCT04244253 completed (completion date 2022-02-25) having MISSED its primary MADRS endpoint at Week 6 (20 mg vs placebo p=0.288). Results posted 2024-09-19. No further MDD development disclosed.
- metOPC-64005 Phase 2 adult ADHD trial (NCT03324581, n=239) met its primary CAARS-O:SV endpoint vs placebo (p=0.0101); ADHD development later discontinued.
- Phase 2 MDD trial NCT04244253 started (first patient / study start date) in Japan.
OPC-64005 for Major depressive disorder
DiscontinuedDiscontinuedMajor depressive disorder indication →
Phase 2 development for major depressive disorder. The Phase 2 trial NCT04244253 (randomized, double-blind, placebo-controlled, 273 patients across 69 sites in Japan) completed on 2022-02-25 and MISSED its primary efficacy endpoint: the OPC-64005 20 mg group did not show statistically significant superiority over placebo on mean change from baseline in MADRS total score at Week 6 (difference -1.1 points, 95% CI -3.3 to 1.0, p=0.288). Results were posted to ClinicalTrials.gov on 2024-09-19. No successor MDD program has been disclosed; recorded as discontinued (negative result deliberately tracked).
Readouts
- 2024-09-19ReportedFull resultsmissedNCT04244253
OPC-64005 Phase 2 MDD trial (NCT04244253, Japan, n=273) missed its primary MADRS endpoint at Week 6 (20 mg vs placebo p=0.288).
- 2021-10-29ReportedFull resultsmetNCT03324581
OPC-64005 Phase 2 adult ADHD trial (NCT03324581, n=239) met its primary CAARS-O:SV endpoint vs placebo (p=0.0101); ADHD development later discontinued.
Clinical trials
NCT04244253Phase 2Completedn=273
A Randomized, Multi-center, Double-blind, Placebo-controlled, Parallel-group Comparison Trial to Assess Efficacy and Safety of OPC-64005 in Patients With Major Depressive Disorder
missedprimaryMean change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 6 — OPC-64005 20 mg: -10.7 (SE 0.8); OPC-64005 10 mg: -11.2 (SE 1.5); placebo: -9.5 (SE 0.8). 20 mg vs placebo difference -1.1 (95% CI -3.3 to 1.0) (0.288 (20 mg vs placebo))
Primary endpoint MISSED: the OPC-64005 20 mg group did not demonstrate statistically significant superiority over placebo on MADRS change from baseline at Week 6 (MMRM; difference -1.1, p=0.288). Trial conducted in Japan (273 patients, 69 sites). Results posted to ClinicalTrials.gov 2024-09-19.
NCT03324581Phase 2Completedn=239
A Phase 2, Multicenter, Randomized, Double-blind, Active- and Placebo-controlled Trial of the Safety and Efficacy of OPC-64005 in the Treatment of Adult Attention-deficit/Hyperactivity Disorder
metprimaryChange from baseline in CAARS-O:SV 18-item ADHD Symptoms Total Score at Day 56 — OPC-64005: -19.4 (SD 17.79); atomoxetine: -20.2 (SD 13.24); placebo: -10.3 (SD 13.52). OPC-64005 vs placebo difference -6.61 (95% CI -11.6 to -1.60) (0.0101 (OPC-64005 vs placebo); atomoxetine vs placebo p=0.0033)
Secondary (non-MDD) ADHD trial. Primary endpoint MET: OPC-64005 significantly improved CAARS-O:SV ADHD symptoms vs placebo at Day 56 (p=0.0101), comparable to the active comparator atomoxetine (OPC-64005 vs atomoxetine p=0.7554, not significant). Despite the positive result, ADHD development was subsequently discontinued.
Identifiers
Sources
- A Phase 2 Trial of OPC-64005 for Major Depressive Disorder — ClinicalTrials.gov
- NCT04244253 Study Protocol — OPC-64005 in Major Depressive Disorder — ClinicalTrials.gov (NIH)
- OPC-64005 — Wikipedia
- The Safety and Efficacy of OPC-64005 in the Treatment of Adult Attention-deficit/Hyperactivity Disorder (NCT03324581) — ClinicalTrials.gov