ACT-539313 / Idorsia - LARVOL DELTA

Discovery of Nivasorexant (ACT-539313): The First Selective Orexin-1 Receptor Antagonist (SO1RA) Investigated in Clinical Trials. (PubMed, J Med Chem) - "Efficacy in a rat model of schedule-induced polydipsia supported the decision to select the compound as a preclinical candidate. Nivasorexant (20) represents the first SO1RA to enter clinical development and completed a first proof of concept phase II clinical trial in binge eating disorder in 2022."

Journal • Binge Eating Disorder • CNS Disorders • Mood Disorders • Psychiatry • Substance Abuse

Effect of nivasorexant (ACT-539313), a selective orexin-1-receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects. (PubMed, Pharmacol Res Perspect) - P1 | "In vivo, a single-center, open-label, fixed-sequence study was performed in healthy adults to explore the effect of 100 mg nivasorexant administered twice daily (b.i.d.) on the pharmacokinetics (PK) of flurbiprofen (50 mg, CYP2C9), omeprazole (20 mg, CYP2C19), midazolam (2 mg, CYP3A4) making use of a cocktail approach. administration. Clinicaltrials.gov ID: NCT05254548."

Journal • Preclinical • Binge Eating Disorder • CNS Disorders • CYP2C19 • CYP2C9

A Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on What the Body Does to Flurbiprofen, Omeprazole, Midazolam in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Idorsia Pharmaceuticals Ltd. | Recruiting ➔ Completed

Trial completion

"$IDIA: ACT-539313 Ph2 data in BED - Q2'22 $QURE: AMT-130 Ph1/2 data in Huntington's - Q2'22 Conferences #ECCMID2022 - 23-26 Apr #AAN22 - 24-26 Apr #ATTD2022 - 27-30 Apr #ARVO - 1-5 May (3/3)" (@KempenLS)

Huntington's Disease • Movement Disorders

Multicenter Study to Evaluate the Efficacy and Safety of Oral ACT-539313 in the Treatment of Adults With Moderate to Severe Binge Eating Disorder (clinicaltrials.gov) - P2 | N=136 | Completed | Sponsor: Idorsia Pharmaceuticals Ltd. | Active, not recruiting ➔ Completed

Trial completion • Binge Eating Disorder • CNS Disorders

A Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on What the Body Does to Flurbiprofen, Omeprazole, Midazolam in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: Idorsia Pharmaceuticals Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on What the Body Does to Flurbiprofen, Omeprazole, Midazolam in Healthy Subjects (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Idorsia Pharmaceuticals Ltd.

New P1 trial

Multicenter Study to Evaluate the Efficacy and Safety of Oral ACT-539313 in the Treatment of Adults With Moderate to Severe Binge Eating Disorder (clinicaltrials.gov) - P2; N=136; Active, not recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Binge Eating Disorder • CNS Disorders

Multicenter Study to Evaluate the Efficacy and Safety of Oral ACT-539313 in the Treatment of Adults With Moderate to Severe Binge Eating Disorder (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Binge Eating Disorder • CNS Disorders

Multicenter Study to Evaluate the Efficacy and Safety of Oral ACT-539313 in the Treatment of Adults With Moderate to Severe Binge Eating Disorder (clinicaltrials.gov) - P2; N=120; Not yet recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.

Clinical • New P2 trial • Binge Eating Disorder • CNS Disorders

Multiple-dose clinical pharmacology of the selective orexin-1 receptor antagonist ACT-539313. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Multiple-dose administration of ACT-539313 was safe and well tolerated up to multiple doses of 200 mg b.i.d. The drug's PK properties as well as the pattern of a decrease in stress-related symptoms after the CO challenge support further investigations of ACT-539313."

Clinical • Journal • Anesthesia • Mood Disorders • Pain • Psychiatry • Tobacco Addiction

First - in - man study with ACT - 539313, a novel selective orexin-1 receptor antagonist. (PubMed, Br J Clin Pharmacol) - "ACT-539313 exhibits good safety and tolerability at single doses of up to and including 400 mg that warrant further investigations."

Journal

Impact of the Selective Orexin-1 Receptor Antagonist ACT-539313 on the Pharmacokinetics of the CYP3A Probe Drug Midazolam in Healthy Male Subjects. (PubMed, J Clin Pharmacol) - "No treatment-related effects on vital signs, clinical laboratory, and electrocardiogram were observed. In summary, the observed corresponding decrease of both the validated, exogenous (midazolam/1-hydroxymidazolam ratio) and a frequently used endogenous (6β-CR) marker of CYP3A activity is indicative of CYP3A inhibition occurring after ACT-539313 treatment."

Clinical • Journal • PK/PD data

Effects of the selective orexin 1 receptor antagonists ACT-335827 and ACT-539313 on reinstatement of extinguished cocaine seeking in rats (WFSBP 2019) - "Conclusion Overall, both OXR1 antagonists were able to reduce the reinstatement of extinguished cocaine seeking triggered by different reinstatement conditions. The discrepancy of effectiveness between both drugs on cue-induced reinstatement remains hitherto unexplained."

Preclinical

The selective orexin 1 receptor antagonist ACT-539313 has anxiolytic-like effects in rats and pigs (WFSBP 2019) - "Conclusion Upon acute oral administration ACT-539313 exerted consistent anxiolytic-like effects in a variety of tests modeling different aspects of human anxiety disorders in both rats and pigs. Based on these results, OXR1 antagonists may have the potential to treat anxiety in humans."

Preclinical