OPC-64005 · program

OPC-64005 for Major depressive disorder

DiscontinuedDiscontinuedOtsuka Pharmaceutical Co., Ltd. (4578.T)

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).

Data current as of

Development timeline

DiscontinuedFeb 2022 – Sept 2024
  1. 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).
  2. 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.
Phase 2Mar 2020 – Oct 2021
  1. 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.
  2. Phase 2 MDD trial NCT04244253 started (first patient / study start date) in Japan.

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 in Major depressive disorder

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

Started Mar 2020· Primary completion Feb 2022· 📍 1 site across 1 country (Japan)

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

Started Nov 2017· Primary completion Oct 2018· 📍 26 sites across 1 country (United States)

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.

Formulations

FormulationRouteRegimenPharmacokinetics
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
OralOnce dailyTmax 3 h

Mechanism of action (compound-wide)

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.

TargetActionAffinity
SERTprimarySLC6A4Reuptake inhibitor—ⓘ
DATSLC6A3Reuptake inhibitor—ⓘ
NETSLC6A2Reuptake inhibitor—ⓘ

← Full OPC-64005 compound page (identity, identifiers, all indications)

Sources

  1. A Phase 2 Trial of OPC-64005 for Major Depressive Disorder — ClinicalTrials.gov
  2. NCT04244253 Study Protocol — OPC-64005 in Major Depressive Disorder — ClinicalTrials.gov (NIH)
  3. OPC-64005 — Wikipedia
  4. The Safety and Efficacy of OPC-64005 in the Treatment of Adult Attention-deficit/Hyperactivity Disorder (NCT03324581) — ClinicalTrials.gov