BI 1358894 / Boehringer Ingelheim - LARVOL DELTA

Efficacy and Safety of BI 1358894 in Patients With Borderline Personality Disorder: Results of a Phase 2 Randomized, Placebo-Controlled, Parallel Group Dose-Ranging Trial. (PubMed, J Clin Psychiatry) - P2 | "More targeted populations, alternative outcome assessments, and additional measures to minimize placebo effects should be considered for future trials. Trial Registration: ClinicalTrials.gov identifier: NCT04566601."

Clinical • Journal • P2 data • Borderline Personality Disorder • CNS Disorders • Mood Disorders • Personality Disorder • Psychiatry • Suicidal Ideation

Safety of BI 1358894 in patients with major depressive disorder: Results and learnings from a phase II randomized decentralized clinical trial. (PubMed, Clin Transl Sci) - "A fully remote, interventional DCT was feasible in MDD, and was well perceived by trial participants. Learnings related to recruitment optimization and trial design should be considered for future interventional DCTs."

Clinical • Journal • P2 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

TRPC4/5 inhibitors: Phase I results and proof of concept studies. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "Furthermore, we highlight an imaging study that investigated the acute effects of BI 1358894 and showed reduced activation in several brain regions involved in emotional processing. We conclude that these findings demonstrate a critical role for TRPC4 and TRPC5 in emotional processing, even though it remains an open question if the biological signatures of TRPC4/5 inhibition reported here translate into clinical efficacy and indicate that a TRPC4/5 inhibitor might provide a more effective treatment of internalizing disorders."

Journal • P1 data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Safety, Tolerability, and Pharmacokinetics of Oral BI 1358894 in Healthy Japanese Male Volunteers. (PubMed, Clin Drug Investig) - P1 | "BI 1358894 was well tolerated with a favorable pharmacokinetic profile in Japanese male HVs, similar to findings from a previous study in Caucasian male HVs."

Journal • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry • Sleep Disorder

A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder. (PubMed, Drugs) - "Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders."

Journal • Review • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood (clinicaltrials.gov) - P1 | N=29 | Terminated | Sponsor: Boehringer Ingelheim | Trial completion date: May 2024 ➔ Feb 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2024 ➔ Feb 2024; Company decision

Trial completion date • Trial primary completion date • Trial termination

A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression (clinicaltrials.gov) - P2 | N=389 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

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

A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

Effects of Single and Multiple Ascending Doses of BI 1358894 in Healthy Male Volunteers on Safety, Tolerability and Pharmacokinetics: Two Phase I Partially Randomised Studies. (PubMed, CNS Drugs) - P1 | "These studies demonstrate that BI 1358894 is well tolerated in healthy male volunteers following single and multiple doses, with no dose dependency observed in DRAE frequency. BI 1358894 exposure increased dose dependently in both the SAD and MAD studies, with higher exposure of BI 1358894 observed in the fed state."

Journal • P1 data • PK/PD data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Effect of BI 1358894 on Cholecystokinin-Tetrapeptide (CCK-4)-Induced Anxiety, Panic Symptoms, and Stress Biomarkers: A Phase I Randomized Trial in Healthy Males. (PubMed, CNS Drugs) - P1 | "Overall, BI 1358894 reduced psychological and physiological responses to CCK-4 compared with placebo, as measured by PSS, subjective EVAS and objectively measured stress biomarkers. BI 1358894 had a positive safety profile, and single oral doses were well tolerated by the healthy volunteers. This trial (NCT03904576/1402-0005) was registered on Clinicaltrials.gov on 05.04.19."

Biomarker • Journal • P1 data • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression (clinicaltrials.gov) - P2 | N=389 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

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

A Study to Test Whether Taking BI 1358894 for 8 Weeks Helps Adults With Post-traumatic Stress Disorder (clinicaltrials.gov) - P2 | N=318 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

BI 1358894 in patients with major depressive disorder: preliminary results from an interventional decentralised clinical trial (ECNP 2023) - "Preliminary results indicate that adjunctive daily BI 1358894 treatment over 6 weeks was well-tolerated and demonstrated a favourable safety profile. Monitoring of medication adherence and compliance via technology has huge advantages but also some limitations."

Clinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry • Suicidal Ideation

Learnings from the execution of the first interventional decentralised clinical trial study in major depressive disorder: a phase II trial (ECNP 2023) - P2 | "Aim Here, we aimed to identify key learnings from this interventional decentralised clinical trial evaluating BI 1358894 in treating patients with MDD, which was designed for direct comparison to a traditional site-based trial evaluating the effects of BI 1358894 in MDD that recruited patients from multiple countries (Phase II, NCT04521478/1402-0011)...Also, ensuring the engagement of key players early in protocol development is important. Optimisation of the recruitment process is required to ensure future decentralised clinical trials can benefit from inclusion of broader and more diverse patient populations."

Clinical • P2 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Test Whether Taking BI 1358894 for 8 Weeks Helps Adults With Post-traumatic Stress Disorder (clinicaltrials.gov) - P2 | N=318 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

Pharmaceutical Pipeline of BI 1358894: Clinical Evidence for an Emerging Drug for the Treatment of Mental Health Conditions (ASCP 2023) - P2 | "A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression. BI 1358894 was well tolerated across the clinical Phase I studies; BI 1358894 attenuated amygdala hyperactivation in response to negative faces and scenes. These data support further investigation of this mechanism of action for patients with symptomatology associated with amygdala hyperreactivity. A Phase II study in BPD was recently clinically completed."

Clinical • Borderline Personality Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Personality Disorder • Post-traumatic Stress Disorder • Psychiatry

A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder (clinicaltrials.gov) - P2 | N=390 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Borderline Personality Disorder • CNS Disorders • Mood Disorders • Personality Disorder

A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder (clinicaltrials.gov) - P2 | N=390 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Borderline Personality Disorder • CNS Disorders • Mood Disorders • Personality Disorder

A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder (clinicaltrials.gov) - P2 | N=355 | Recruiting | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Recruiting

Enrollment open • Borderline Personality Disorder • CNS Disorders • Mood Disorders • Personality Disorder

The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder. (PubMed, Eur Neuropsychopharmacol) - "Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder (clinicaltrials.gov) - P2 | N=355 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Borderline Personality Disorder • CNS Disorders • Mood Disorders • Personality Disorder

A Home-based Study Using Mobile Technology to Test Whether BI 1358894 is Effective in People With Depression (clinicaltrials.gov) - P2 | N=45 | Terminated | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Terminated; Recruitment challenges

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

A Home-based Study Using Mobile Technology to Test Whether BI 1358894 is Effective in People With Depression (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Suspended ➔ Active, not recruiting

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