icalcaprant (CVL-354) / AbbVie - LARVOL DELTA

A Study to Assess the Mass Balance of Oral ABBV-1354 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Assess Adverse Events and Change in Disease Activity of Oral Icalcaprant in Adult Participants With Bipolar I or II Disorder (clinicaltrials.gov) - P2 | N=195 | Not yet recruiting | Sponsor: AbbVie | Trial completion date: Oct 2026 ➔ Nov 2027 | Initiation date: May 2025 ➔ Feb 2026 | Trial primary completion date: Oct 2026 ➔ Nov 2027

Adverse events • Trial completion date • Trial initiation date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Study to Assess the Mass Balance of Oral ABBV-1354 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: AbbVie

New P1 trial

Development of a Kappa Opioid Receptor Antagonist (CVL-354) to Mitigate the Physical Symptoms of Opioid Withdrawal to Facilitate Abrupt Opioid Discontinuation in Adults (CPDD 2025) - No abstract available

Clinical • Addiction (Opioid and Alcohol)

NIDA’s “Ten Most Wanted” Targets for Development in Response to the Opioid Crisis- Advances Made Since 2019 (CPDD 2025) - "Frank Gray (Indivior) will present on the development of the selective orexin-1 receptor antagonist, INDV-2000, for OUD...Georgette Suidan (AbbVie) will present on the development of kappa opioid antagonist, CVL-354, for opioid withdrawal...Nicholas Cosford (Sanford Burnham Prebys Medical Discovery Institute) will present progress on the development of metabotropic glutamate 2/3 receptor (mGluR2/3) positive allosteric modulators (PAMs) for OUD and other SUD indications. Beyond highlighting these respective targets and projects, this symposium will bring attention to those targets from the original ten most wanted paper that have yet to be advanced and foster discussion focused on new potential therapeutic targets."

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

529 DDI ITZ: A Study to Assess Change in How Oral Icalcaprant With Itraconazole Moves Through the Body in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion

A Single Dose Study to Assess Adverse Events and How Oral Icalcaprant Moves Through the Body in Healthy Adult Japanese and Han Chinese Participants (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Adverse events • Trial completion

A Single Dose Study to Assess Adverse Events and How Oral Icalcaprant Moves Through the Body in Healthy Adult Japanese and Han Chinese Participants (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed

529 DDI ITZ: A Study to Assess Change in How Oral Icalcaprant With Itraconazole Moves Through the Body in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

529 DDI ITZ: A Study to Assess Change in How Oral Icalcaprant With Itraconazole Moves Through the Body in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: AbbVie

New P1 trial

528 Asian PK: A Single Dose Study to Assess Adverse Events and How Oral Icalcaprant Moves Through the Body in Healthy Adult Japanese and Han Chinese Participants (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: AbbVie

Adverse events • New P1 trial

A Study to Assess Adverse Events and Change in Disease Activity of Oral Icalcaprant in Adult Participants With Bipolar I or II Disorder (clinicaltrials.gov) - P2 | N=237 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P2 trial • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Cerevel Therapeutics, LLC | Recruiting ➔ Completed

Trial completion • Substance Abuse

Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Cerevel Therapeutics, LLC

Trial completion date • Trial primary completion date • Substance Abuse

Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Cerevel Therapeutics, LLC | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Feb 2024 ➔ Jun 2024

Trial completion date • Trial primary completion date • Substance Abuse

Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Cerevel Therapeutics, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Substance Abuse

CVL-354-1001: A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

CVL-354-1001: A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants (clinicaltrials.gov) - P1 | N=74 | Active, not recruiting | Sponsor: Cerevel Therapeutics, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Evaluation of Kappa and Mu Opioid Receptor Occupancy by CVL-354 Using PET in Nonhuman Primates (ACNP 2022) - "These data confirm dose-dependent target binding of CVL-354 to both KOR and MOR receptors in nonhuman primates. The results also confirm greater selectivity for the KOR. CVL-354 consistently demonstrated greater affinity towards KOR than MOR (10-40 fold) across the various preclinical evaluations of receptor affinity/activity"

Addiction (Opioid and Alcohol)

CVL-354, a Novel, Brain Penetrant and Selective Kappa Opioid Receptor Antagonist (ACNP 2022) - "In vitro and in vivo pharmacology assays demonstrated that CVL-354 is a novel, brain-penetrant, potent and selective kappa opioid receptor (KOR) antagonist. Additionally, CVL-354 reverses KOR agonist induced deficits in motivation."

Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Substance Abuse

A novel, Short-Acting Kappa Opioid Receptor Antagonist Blocks the Analgesic Effects of U50,488 and Attenuates Symptoms of Spontaneous Oxycodone Withdrawal in Rats (ACNP 2022) - "These data demonstrate that CVL-354 has KOR antagonist actions in thermal pain assays for at least 4, but less than 24, hours, and that it is effective at reducing somatic withdrawal signs in a model of spontaneous oxycodone withdrawal model. Intriguingly, lofexidine treatment suppressed locomotor activity and exacerbated levels of the stress biomarker, corticosterone. CVL-354 did not produce these negative effects, suggesting that KOR antagonism may provide better overall efficacy for mitigation of opioid withdrawal symptoms."

Preclinical • Addiction (Opioid and Alcohol) • Mood Disorders • Pain • Psychiatry

Positron Emission Tomography (PET) Trial to Evaluate Target Occupancy of CVL-354 at Kappa and Mu Opioid Receptors in Brain Following Oral Dosing (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Cerevel Therapeutics, LLC

New P1 trial • Substance Abuse

A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants (clinicaltrials.gov) - P1; N=74; Recruiting; Sponsor: Cerevel Therapeutics, LLC

Clinical • New P1 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry