AZD4041 / AstraZeneca, Eolas Therap - LARVOL DELTA

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2). (clinicaltrials.gov) - P1 | N=15 | Terminated | Sponsor: AstraZeneca | Phase classification: P2 ➔ P1

Phase classification • Substance Abuse

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2). (clinicaltrials.gov) - P2 | N=15 | Terminated | Sponsor: AstraZeneca | N=100 ➔ 15 | Trial completion date: Dec 2025 ➔ Jul 2024 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jul 2024; Study terminated due to discontinuation of the AZD4041 clinical development program for OUD.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Substance Abuse

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2). (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2026 ➔ Dec 2025 | Trial primary completion date: May 2026 ➔ Dec 2025

Trial completion date • Trial primary completion date • Substance Abuse

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2). (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Substance Abuse

Drug-Drug Interaction and Safety of AZD4041 Study (Part 1) and Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AZD4041 Study in Opioid Use Disorder (Part 2). (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Substance Abuse

Translational Studies of AZD4041, a First In-Class Selective Orexin 1 Receptor Antagonist for the Treatment of Opioid Use Disorder (ACNP 2023) - "AZD4041 demonstrated target engagement and efficacy in preclinical models of OUD at RO >65%. Studies in humans showed a good safety profile with clinical doses predicted to have receptor occupancies of greater than 84% at steady state. AZD4041 is considered a promising drug candidate with a strong underlying rationale supporting its further development as a novel and differentiated treatment for OUD."

Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse

A Study to Assess the Effect of AZD4041 on Respiratory Drive in Recreational Opioid Users. (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion • Substance Abuse

A Study to Assess the Effect of AZD4041 on Respiratory Drive in Recreational Opioid Users. (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Substance Abuse

A Safety Study of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion • Substance Abuse

A Safety Study of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: AstraZeneca | N=36 ➔ 48

Enrollment change • Substance Abuse

A Safety Study of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Substance Abuse

A Safety Study of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: MedImmune LLC

New P1 trial • Substance Abuse

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Completed; Sponsor: AstraZeneca; Recruiting ➔ Completed

Clinical • Trial completion • Tobacco Cessation

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: AstraZeneca; Trial completion date: Apr 2021 ➔ Sep 2021; Trial primary completion date: Apr 2021 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Tobacco Cessation

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: AstraZeneca; Trial completion date: Oct 2020 ➔ Feb 2021; Trial primary completion date: Oct 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • Tobacco Cessation

[VIRTUAL] Conventional Rodent Nicotine Self-Administration Procedures Over-Estimate Efficacious Exposures of Smoking Cessation Drugs in Human Smokers (ACNP 2020) - "We also examined the effects of AZD4041 on responding for the standard and higher doses of nicotine and used these data to estimate efficacious exposures in human smokers...Specifically, the nicotinic acetylcholine receptor partial agonist varenicline, the CB1 receptor antagonist rimonabant, the 5-HT2c receptor agonist lorcaserin and the triple re-uptake inhibitor bupropion decreased nicotine intake by rats across multiple laboratories... These findings suggest that the rat IV nicotine self-administration procedure can reliably detect compounds that have efficacy in promoting smoking cessation in humans. However, standard iterations of the self-administration procedure that employ a unit dose of nicotine (0.03 mg /kg/infusion) that sustains maximal rates of responding by rats consistently over-estimates the exposures of compounds necessary to detect efficacy in human smokers. Recently, it was shown self-administration of doses of nicotine higher than 0.03 mg /kg/..."

Preclinical • Alzheimer's Disease • CNS Disorders • Tobacco Cessation

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: AstraZeneca; Trial completion date: Jul 2020 ➔ Oct 2020; Trial primary completion date: Jul 2020 ➔ Oct 2020

Clinical • Trial completion date • Trial primary completion date • Tobacco Cessation

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: AstraZeneca; Trial completion date: Apr 2020 ➔ Jul 2020; Trial primary completion date: Apr 2020 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4041 in Healthy Volunteers (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open