EMB-001 · program

EMB-001 (metyrapone/oxazepam) for Cocaine use disorder

Phase 2UnknownEmbera NeuroTherapeutics, Inc.

Indications for EMB-001: Cocaine use disorder · Phase 2 Tobacco use disorder · Discontinued

EMB-001 (metyrapone/oxazepam) for moderate-to-severe cocaine use disorder, Embera's lead indication. After a 45-subject academic-era pilot (2007-08), Phase 1 safety/PK (2015), a Phase 1b cocaine-interaction study (2016-17, no serious AEs with IV cocaine) and a 2018 formulation-bridging study, the NIDA-funded randomized, double-blind, placebo-controlled Phase 2 (NCT04501874; 720/24 mg BID x 12 weeks + 1-week taper; n=82) ran 2020-07-29 to 2022-07-27. Results posted to ClinicalTrials.gov on 2026-09-21 show the primary endpoint (continuous cocaine abstinence over the final 3 weeks) was not met: 2/41 vs 0/41, p=0.092. No company announcement of the result or of next steps has been found; the program appears dormant.

Data current as of

Development timeline

Phase 2Jul 2020 – Sept 2026
  1. missedPhase 2 EMB-001 in cocaine use disorder misses primary endpoint: continuous abstinence weeks 11-13 in 2/41 (EMB-001) vs 0/41 (placebo), p=0.092.
  2. Phase 2 study completed (primary completion 2022-07-27, study completion 2022-10-15). No follow-on trial or company statement since; results (primary not met) posted 2026-09-21.
  3. Trial (portion) completedPhase 2 EMB-001 cocaine use disorder study completes
  4. Phase 2 NCT04501874 started; first subjects dosed announced 2020-08-31.
  5. Trial startedPhase 2 study of EMB-001 in cocaine use disorder starts
Phase 1Mar 2015 – Jun 2020
  1. FinancingEmbera completes $1.2 million Series B financing↗
  2. First registered EMB-001 study (NCT02406066, Phase 1 SAD/MAD in smokers, NIDA collaborator) started March 2015 (month precision on the registry).

Readouts

  • 2026-09-21ReportedRegistry resultsmissedNCT04501874

    Phase 2 EMB-001 in cocaine use disorder misses primary endpoint: continuous abstinence weeks 11-13 in 2/41 (EMB-001) vs 0/41 (placebo), p=0.092.

Clinical trials in Cocaine use disorder

NCT04501874ERL-003Phase 2Completedn=82

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Safety and Efficacy of EMB 001 in Subjects With Moderate-to-Severe Cocaine Use Disorder

Started Jul 2020· Primary completion Jul 2022· 📍 4 sites across 1 country (United States)

missedContinuous abstinence from cocaine use, Weeks 11-13 (TLFB confirmed by urine benzoylecgonine) (0.092)

2/41 participants abstinent on EMB-001 vs 0/41 on placebo; logistic regression p=0.092 (not significant). 18/41 and 19/41 completed. Secondary: weekly cocaine-use days fell 0.6 (EMB-001) vs 1.2 (placebo); CCQ-Brief craving fell -1.62 vs -2.63 (placebo numerically better on both).

NCT03404817ERL-PK001Phase 1Completedn=9

Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations

Started Mar 2018· Primary completion Jun 2018· 📍 1 site across 1 country (United States)

NCT02856854ERL-002Phase 1Completedn=18

A Phase 1b, Randomized, Double-Blinded, Multiple-Dose, Placebo Controlled, Crossover Study To Evaluate The Safety, Tolerability And Pharmacokinetic Effects Of A Metyrapone And Oxazepam Combination (EMB-001) When Co-Administered With Cocaine

Started Jul 2016· Primary completion Feb 2017· 📍 1 site across 1 country (United States)

NCT02406066ERL-001Phase 1Completedn=24

Phase 1 Combined Single and Multiple Rising Dose Study of the Safety and Pharmacokinetics of Metyrapone/Oxazepam Combination (EMB-001)

Started Mar 2015· Primary completion Dec 2015· 📍 2 sites across 1 country (United States)

NCT00567814ECA-001UnknownCompletedn=45

A Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Two Dose Combinations of Metyrapone and Oxazepam in the Treatment of Cocaine Addiction

Started Dec 2007· Primary completion Nov 2008

Formulations

FormulationRouteRegimenPharmacokinetics
EMB-001 oral capsule (metyrapone 720 mg / oxazepam 24 mg twice daily)
Phase 2 cocaine use disorder: 720 mg metyrapone / 24 mg oxazepam PO BID for 12 weeks then 1-week taper (NCT04501874). Smoking study: same dose BID, total daily 1440 mg metyrapone / 48 mg oxazepam (NCT04933916); the Rose Research Center registration describes 240 mg/8 mg capsules, 3 capsules per dose (NCT04868253). Phase 1 SAD/MAD in smokers: 270/12, 540/24 and 720/24 mg BID for ~1 week (NCT02406066).
OralTwice daily—

Mechanism of action (compound-wide)

Dual mechanism aimed at the stress response implicated in relapse: metyrapone inhibits adrenal 11-beta-hydroxylase (CYP11B1), the final step of cortisol synthesis, lowering stress-driven cortisol; oxazepam is a benzodiazepine that positively modulates GABA-A receptors (anxiolytic). Sponsor describes it as reducing drug-, cue- and stressor-induced stress-system activity that contributes to relapse.

TargetActionAffinity
CYP11B1primaryCYP11B1Inhibitor—ⓘ
GABA-A receptorPAM—ⓘ

← Full EMB-001 compound page (identity, identifiers, all indications)

Sources

  1. Embera NeuroTherapeutics Announces First Subject Dosed in Phase 2 Study of EMB-001 in Cocaine Use Disorder (2020-08-31) — Embera NeuroTherapeutics (Business Wire via BioSpace)
  2. NCT00567814 (ECA-001) - metyrapone/oxazepam pilot in cocaine addiction — ClinicalTrials.gov (U.S. National Library of Medicine)
  3. NCT02406066 (ERL-001) - Phase 1 SAD/MAD of EMB-001 in smokers — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT02856854 (ERL-002) - Phase 1b EMB-001 cocaine interaction study — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. NCT03404817 (ERL-PK001) - comparative bioavailability/food effect of two EMB-001 formulations — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. NCT04501874 (ERL-003) - Phase 2 EMB-001 in moderate-to-severe cocaine use disorder (results posted 2026-09-21) — ClinicalTrials.gov (U.S. National Library of Medicine)
  7. PDB 7E7F - Human CYP11B1 mutant in complex with metyrapone (PMID 34485929) — RCSB Protein Data Bank