Lu AF11167 / Lundbeck - LARVOL DELTA

A double-blind, randomized, placebo-controlled proof of concept study of the efficacy and safety of Lu AF11167 for persistent negative symptoms in people with schizophrenia. (PubMed, Eur Neuropsychopharmacol) - P2 | "Neither dose group showed significant improvements versus placebo on any of the secondary efficacy measures exploring effect of treatment on overall symptomology, negative symptoms, positive symptoms, or functioning. Administration of Lu AF11167 was safe and well tolerated and adverse events were not a major reason for withdrawal from the study."

Clinical • Journal • CNS Disorders • Psychiatry • Schizophrenia

Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia (clinicaltrials.gov) - P2; N=168; Terminated; Sponsor: H. Lundbeck A/S; N=240 ➔ 168; Trial completion date: Feb 2021 ➔ Sep 2020; Recruiting ➔ Terminated; Trial primary completion date: Feb 2021 ➔ Aug 2020; Lack of efficacy based on interim analysis

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Psychiatry • Schizophrenia

Flexible-dose Long-term Extension Study of Lu AF11167 in Patients With Schizophrenia With Prominent Negative Symptoms (clinicaltrials.gov) - P2; N=96; Terminated; Sponsor: H. Lundbeck A/S; N=240 ➔ 96; Trial completion date: Jul 2021 ➔ Sep 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Jul 2021 ➔ Sep 2020; Lack of efficacy based on the interim analysis in the 17972A study

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Psychiatry • Schizophrenia

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. (PubMed, CNS Spectr) - "Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved..."

Journal • CNS Disorders • Schizophrenia

Lundbeck discontinues phase II proof of concept study of Lu AF11167 in patients with negative symptoms of schizophrenia (Lundbeck Press Release) - "H. Lundbeck A/S (Lundbeck) announces the decision to discontinue the phase II proof of concept clinical study of Lu AF11167 in patients with schizophrenia, who are experiencing persistent negative symptoms (NCT03793712). The decision to stop the trial is based on the results of a futility interim analysis, which concluded that the trial is unlikely to achieve statistical significance on its primary endpoint, mean change from baseline to week 12 on the Brief Negative Symptom Scale (BNSS). The recommendation to stop the trial is not based on safety concerns."

Trial termination • CNS Disorders • Schizophrenia

Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: H. Lundbeck A/S; Trial completion date: Nov 2020 ➔ Feb 2021; Trial primary completion date: Nov 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Schizophrenia

Flexible-dose Long-term Extension Study of Lu AF11167 in Patients With Schizophrenia With Prominent Negative Symptoms (clinicaltrials.gov) - P2; N=240; Enrolling by invitation; Sponsor: H. Lundbeck A/S; Trial completion date: Dec 2020 ➔ Jul 2021; Trial primary completion date: Dec 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Schizophrenia

A Study Investigating Tablet Formulations of Lu AF11167 in Healthy Subjects (clinicaltrials.gov) - P1; N=33; Completed; Sponsor: H. Lundbeck A/S; Recruiting ➔ Completed

Clinical • Trial completion

Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: H. Lundbeck A/S; Trial completion date: May 2020 ➔ Nov 2020; Trial primary completion date: May 2020 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date

A Study Investigating Tablet Formulations of Lu AF11167 in Healthy Subjects (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: H. Lundbeck A/S

Clinical • New P1 trial

Flexible-dose Long-term Extension Study of Lu AF11167 in Patients With Schizophrenia With Prominent Negative Symptoms (clinicaltrials.gov) - P2; N=240; Enrolling by invitation; Sponsor: H. Lundbeck A/S; Trial completion date: Dec 2019 ➔ Dec 2020; Trial primary completion date: Dec 2019 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date

Flexible-dose Long-term Extension Study of Lu AF11167 in Patients With Schizophrenia With Prominent Negative Symptoms (clinicaltrials.gov) - P2; N=240; Enrolling by invitation; Sponsor: H. Lundbeck A/S

New P2 trial

Pharmacological Treatment of Negative Symptoms: New Findings and Perspectives (EPA 2019) - "...Two dopamine D3-receptor-preferring partial agonists, F17464 (it is in Phase II) and cariprazine (it is already on the market) showed efficacy against positive symptoms, cariprazine has been found also effective against predominant and persistent negative symptoms as compared to risperidone...An example is pimavanserin, which is an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity and at serotonin 5-HT2C receptors with lower binding affinity...This drug has already been approved by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis. An interesting further approach is to discontinue antipsychotic drugs in stable schizophrenia patients with negative symptoms and start a drug for the treatment of negative symptoms, such as MIN-101, a 5HT2 and Sigma 2 antagonist, which demonstrated statistically significant efficacy as a monotherapy; and Lu AF11167 (an inhibitor of a..."

Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: H. Lundbeck A/S

Clinical • New P2 trial