Small Molecule · EMB-001

EMB-001 (metyrapone/oxazepam)

Phase 2Embera NeuroTherapeutics, Inc.

Oral fixed-dose combination of two previously FDA-approved drugs: metyrapone (Metopirone, a cortisol-synthesis inhibitor acting at 11-beta-hydroxylase/CYP11B1) and oxazepam (a benzodiazepine, GABA-A receptor positive modulator). Developed by Embera NeuroTherapeutics (Shreveport, LA / Boston) from discoveries by Nicholas Goeders at LSU Health Shreveport, licensed exclusively to Embera. Rationale: dampen the stress-response (HPA-axis) activity driven by drugs, cues and stressors that precipitates relapse in addiction. Tested in cocaine use disorder (NIDA-funded Phase 2, completed 2022, primary abstinence endpoint not met per registry results posted 2026-09-21) and smoking cessation (open-label Phase 1/2 terminated 2023 for a business decision).

Also known as: EMB-001, EMB 001, metyrapone/oxazepam

Data current as of

Key facts

Modality
Small molecule
Mechanism
CYP11B1 inhibitor
Highest phase
Phase 2
Lead indication
Cocaine use disorder
Developer
Embera NeuroTherapeutics, Inc.
Trials
7 tracked · 11 sites

Mechanism of action#

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—ⓘ

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—

Development timeline#

201620182020202220242026TodayPhase 11 Jun 2020 — Financing — Embera completes $1.2 million Series B financing1 Mar 2015 — phase change — First registered EMB-001 study (NCT02406066, Phase 1 SAD/MAD in smokers, NIDA collaborator) started March 2015 (month precision on the registry).1 Mar 2015 — phase change — Phase 1 SAD/MAD in otherwise healthy regular cigarette smokers (NCT02406066) started March 2015 (month precision).Phase 221 Sept 2026 — readout (missed) — 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=0.092.15 Oct 2022 — phase change — 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 2026-09-21.15 Oct 2022 — Trial (portion) completed — Phase 2 EMB-001 cocaine use disorder study completes29 Jul 2020 — phase change — Phase 2 NCT04501874 started; first subjects dosed announced 2020-08-31.29 Jul 2020 — Trial started — Phase 2 study of EMB-001 in cocaine use disorder startsPhase 1/230 Jun 2021 — Financing — Embera discloses $1.3 million financing from current investors10 Jun 2021 — phase change — Open-label smoking cessation study NCT04933916 started (registered Phase 1/Phase 2; company calls it Phase 2a). First subject dosed announced 2021-06-30.10 Jun 2021 — Trial started — Open-label Phase 2a study of EMB-001 in smoking cessation startsDiscontinued1 May 2023 — phase change — NCT04933916 terminated, why stopped: 'Business decision' (16 enrolled). Inferred program discontinuation; no formal company statement.1 May 2023 — Trial terminated — EMB-001 smoking cessation study terminated (business decision)
Phase change Readout Event UpcomingHover a marker for details.
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.Cocaine use disorder
  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.Cocaine use disorder
  3. Trial (portion) completedPhase 2 EMB-001 cocaine use disorder study completesCocaine use disorder
  4. Phase 2 NCT04501874 started; first subjects dosed announced 2020-08-31.Cocaine use disorder
  5. Trial startedPhase 2 study of EMB-001 in cocaine use disorder startsCocaine use disorder
DiscontinuedMay 2023
  1. NCT04933916 terminated, why stopped: 'Business decision' (16 enrolled). Inferred program discontinuation; no formal company statement.Tobacco use disorder
  2. Trial terminatedEMB-001 smoking cessation study terminated (business decision)Tobacco use disorder
Phase 1/2Jun 2021 – Jun 2021
  1. FinancingEmbera discloses $1.3 million financing from current investorsTobacco use disorder↗
  2. Open-label smoking cessation study NCT04933916 started (registered Phase 1/Phase 2; company calls it Phase 2a). First subject dosed announced 2021-06-30.Tobacco use disorder
  3. Trial startedOpen-label Phase 2a study of EMB-001 in smoking cessation startsTobacco use disorder
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).Cocaine use disorder
  3. Phase 1 SAD/MAD in otherwise healthy regular cigarette smokers (NCT02406066) started March 2015 (month precision).Tobacco use disorder

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

Phase 2UnknownCocaine use disorder indication →

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.

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.

EMB-001 (metyrapone/oxazepam) for Tobacco use disorder#

DiscontinuedDiscontinuedTobacco use disorder indication →

EMB-001 (metyrapone/oxazepam) for smoking cessation / tobacco use disorder. Phase 1 safety/PK was run in otherwise healthy regular smokers (NCT02406066, 2015). An open-label Phase 1/2 ('Phase 2a') study at Rose Research Center, North Carolina (NCT04933916; 720/24 mg BID for 12 weeks; funded by the Foundation for a Smoke-Free World and a $1.3M investor financing) dosed its first subject in June 2021 with topline guided for Q1 2022, but was terminated for a business decision after enrolling 16 of up to 50 subjects (completed 2023-05-01). No efficacy results have been posted or announced.

Clinical trials#

NCT04933916ERL-T002Phase 1/2Discontinuedn=16

Efficacy and Safety of Combination EMB-001 as a Potential Smoking Cessation Treatment

Started Jun 2021· Primary completion Apr 2023· 2 sites across 1 country

United States

NCT04868253ERL-T002Phase 2/3Unknownn=25

Efficacy and Safety of Combination EMB-001 as a Potential Smoking Cessation Treatment

Started May 2021· Primary completion Dec 2021· 1 site across 1 country

United States

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

Show all 7 trials

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

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. Embera NeuroTherapeutics Announces First Subject Dosed in Phase 2a Study of EMB-001 in Smoking Cessation (2021-06-30) — Embera NeuroTherapeutics (Business Wire via BioSpace)
  3. NCT00567814 (ECA-001) - metyrapone/oxazepam pilot in cocaine addiction — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT02406066 (ERL-001) - Phase 1 SAD/MAD of EMB-001 in smokers — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. NCT02856854 (ERL-002) - Phase 1b EMB-001 cocaine interaction study — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. NCT03404817 (ERL-PK001) - comparative bioavailability/food effect of two EMB-001 formulations — ClinicalTrials.gov (U.S. National Library of Medicine)
  7. 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)
  8. NCT04868253 (ERL-T002) - EMB-001 smoking cessation, Rose Research Center registration — ClinicalTrials.gov (U.S. National Library of Medicine)
  9. NCT04933916 (ERL-T002) - EMB-001 smoking cessation, terminated (business decision) — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. PDB 7E7F - Human CYP11B1 mutant in complex with metyrapone (PMID 34485929) — RCSB Protein Data Bank