INDV-2000 / C4X Discovery, Indivior - LARVOL DELTA

Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder (clinicaltrials.gov) - P2 | N=300 | Active, not recruiting | Sponsor: Indivior Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Aug 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Trial primary completion date • Substance Abuse

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

INDV-2000: A Novel, Non-Opioid, Selective Orexin-1 Receptor Antagonist for the Treatment of Opioid Use Disorder (CPDD 2025) - No abstract available

Addiction (Opioid and Alcohol) • Substance Abuse

Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Indivior Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Substance Abuse

Pharmacodynamic, Safety and Pharmacokinetic Effects of Co-Administration of the Selective Orexin-1 Receptor Antagonist INDV-2000 and Buprenorphine in Treatment Seeking Individuals with Opioid Use Disorder (CPDD 2024) - P1 | "They reported use of heroin, fentanyl and/or oxycodone at screening and had positive urine tests for opioids, fentanyl, cocaine, benzodiazepines, amphetamine/methamphetamine and/or cannabis. Co-administration of BUP/NLX and the selective OX1R antagonist INDV-2000 was well tolerated. Participants reported minimal or no withdrawal with INDV-2000 alone after BUP/NLX treatment stopped demonstrating the potential for successful transition paradigms for future larger scale studies."

Clinical • PK/PD data • Addiction (Opioid and Alcohol) • Substance Abuse

Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Indivior Inc.

New P2 trial • Substance Abuse

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Indivior Inc. | Active, not recruiting ➔ Completed | Trial completion date: Nov 2023 ➔ Jul 2023

Trial completion • Trial completion date • Substance Abuse

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Indivior Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Substance Abuse

Study of Potential CYP3A4 Induction by INDV-2000 in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Indivior Inc. | Active, not recruiting ➔ Completed | Trial completion date: Aug 2023 ➔ May 2023

Trial completion • Trial completion date

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Indivior Inc. | Trial completion date: Jul 2023 ➔ Nov 2023 | Trial primary completion date: Apr 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Substance Abuse

Study of Potential CYP3A4 Induction by INDV-2000 in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Indivior Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2023 ➔ Jun 2023

Enrollment closed • Trial primary completion date

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Indivior Inc. | Trial completion date: Apr 2023 ➔ Jul 2023

Trial completion date • Substance Abuse

Study of Potential CYP3A4 Induction by INDV-2000 in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Indivior Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Study of Potential CYP3A4 Induction by INDV-2000 in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Indivior Inc.

New P1 trial

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Indivior Inc. | Trial primary completion date: Dec 2022 ➔ Apr 2023

Trial primary completion date • Substance Abuse

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Indivior Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Substance Abuse

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: Indivior Inc. | Trial completion date: Aug 2023 ➔ Apr 2023 | Trial primary completion date: Aug 2023 ➔ Dec 2022

Trial completion date • Trial primary completion date • Substance Abuse

First in Human Trial of the Non-Opioid Selective Orexin-1 Antagonist INDV-2000 in Healthy Volunteers (CPDD 2022) - P1 | "INDV-2000 is a well-tolerated, well-absorbed, highly selective OX1R antagonist in healthy volunteers after single doses up to 720mg. The pharmacokinetic profile showed dose proportional increases in overall exposure up to 720mg."

Clinical • P1 data • Anesthesia

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1; N=64; Not yet recruiting; Sponsor: Indivior Inc.; Trial completion date: Aug 2022 ➔ Aug 2023; Initiation date: Aug 2021 ➔ Aug 2022; Trial primary completion date: Aug 2022 ➔ Aug 2023

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Substance Abuse

Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder (clinicaltrials.gov) - P1; N=64; Not yet recruiting; Sponsor: Indivior Inc.

New P1 trial • Substance Abuse

INDV-2000 First in Human (clinicaltrials.gov) - P1; N=72; Completed; Sponsor: Indivior Inc.; Recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol)

INDV-2000 First in Human (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Indivior Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Addiction (Opioid and Alcohol)

INDV-2000 First in Human (clinicaltrials.gov) - P1; N=56; Not yet recruiting; Sponsor: Indivior Inc.

Clinical • New P1 trial • Addiction (Opioid and Alcohol)

The role of orexin-1 receptor signaling in demand for the opioid fentanyl. (PubMed, Neuropsychopharmacology) - "Orexin-1 receptor (OxR1) antagonism reduces demand for cocaine and remifentanil, indicating that orexin-based therapies may reduce demand for many classes of abused drugs. Baseline α values predicted the amount of cued reinstatement of fentanyl seeking; this reinstatement behavior was attenuated by SB administration. These results highlight the promise of the orexin system as a treatment target for opioid addiction and emphasize the usefulness of BE procedures in the study of opioid abuse."

Journal

The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task. (PubMed, Brain Res) - "...Here, we investigated the effects of the OxR1 antagonist SB-334867 on response inhibition in a rat version of the stop signal reaction time task...In contrast, this manipulation reduced motivation to perform the task and earn food rewards, consistent with other recent findings. These results add to the growing body of literature implicating OxR1 in the regulation of motivation and suggest that effects of pharmacological compounds such as SB-334867 on drug seeking behavior are not related to effects on response inhibition."

Journal • Preclinical