staccato alprazolam (AZ-002) / Ferrer International, UCB - LARVOL DELTA

A Study to Assess the Time to Onset of Action of Staccato Alprazolam Versus Midazolam and Diazepam in Healthy Participants (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders

Opportunities for and Challenges of Pulmonary Drug Delivery in the Management of Acute Exacerbations of CNS Disorders. (PubMed, CNS Drugs) - "In this review, the potential of PM delivery to address this gap in the management of acute CNS disorders is critically assessed, focusing on Staccato® (loxapine) for agitation, Inbrija® (levodopa) for PD, the investigational drug inhaler device Staccato® (alprazolam) for epilepsy, and other investigational drug inhaler devices. In particular, for epilepsy, on-demand medication that may be administered by patients or caregivers early at seizure onset may translate to improved patient outcomes. To enhance PM management of acute exacerbations of CNS disorders, further research and user training for optimal PM administration are required."

Journal • Review • CNS Disorders • Epilepsy • Insomnia • Migraine • Movement Disorders • Pain • Parkinson's Disease • Sleep Disorder

A Study to Assess the Time to Onset of Action of Staccato Alprazolam Versus Midazolam and Diazepam in Healthy Participants (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: UCB Biopharma SRL

New P1 trial • CNS Disorders

Inhalation as an Efficient Delivery Route of Alprazolam for the Treatment of Acute Seizures: Randomized Study of Staccato® Alprazolam Compared to Oral Alprazolam (AAN 2025) - P1 | "Alprazolam absorption following inhalation with the Staccato® device was fast and supports its use for rapid and early seizure termination. Dose-normalized Cmax was approximately 59% higher after Staccato® alprazolam 2mg vs oral alprazolam 2mg. No clinically relevant difference was observed on dose-normalized AUC."

Clinical • CNS Disorders • Epilepsy • Hypotension

A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures (clinicaltrials.gov) - P3 | N=350 | Recruiting | Sponsor: UCB Biopharma SRL | N=250 ➔ 350

Enrollment change • CNS Disorders • Epilepsy

Inhalation as an Efficient Delivery Route of Alprazolam for the Treatment of Acute Seizures: Randomized Study of Staccato® Alprazolam Relative to Oral Alprazolam (AES 2024) - P1 | "The distribution and elimination of alprazolam following administration by inhalation were comparable to those observed after oral administration. Absorption following inhalation with Staccato® device was very fast and showed that clinically relevant plasma alprazolam concentrations, comparable to the Cmax of oral alprazolam, can be achieved within 2 minutes post-dose. Thus, alprazolam administration via the Staccato® device is an efficient delivery route for the treatment of acute seizures."

Clinical • CNS Disorders • Epilepsy

A Study to Test the Safety and Tolerability of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures (clinicaltrials.gov) - P3 | N=300 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | Trial completion date: May 2026 ➔ Nov 2028 | Trial primary completion date: May 2026 ➔ Nov 2028

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Apr 2024 ➔ Apr 2026 | Trial primary completion date: Apr 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Pulmonary Safety of Staccato® Alprazolam in Healthy Participants and Participants with Mild Asthma: Phase 1, Randomized, Double-blind, Placebo-controlled Trial (AAN 2024) - P1 | "STAP (1mg/2mg) administered 72h apart was well tolerated in healthy participants and those with mild asthma. Minor decreases in FEV1 from baseline were observed with STAP vs placebo; these were not clinically relevant. Cough was the most common respiratory-TEAE."

Clinical • P1 data • Asthma • Cough • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacokinetics of Staccato® Alprazolam in Healthy Adult Participants: Phase 1, Randomized, Placebo-controlled Ethno-bridging Study (AAN 2024) - P1 | "Alprazolam was rapidly absorbed (median Tmax of 1.5–2 min) when administered with the Staccato® device. No ethnic differences were observed based on AUCinf and AUC0-t suggesting no need for dose adjustments. Staccato® alprazolam was generally well tolerated."

Clinical • P1 data • PK/PD data • CNS Disorders • Epilepsy

Pharmacokinetics and Tolerability of Single-dose Staccato® Alprazolam in Adolescents with Epilepsy and Population PK Analysis to Support Dose Selection in Adolescents (AAN 2024) - P1 | "Alprazolam PK following Staccato® administration in adolescents with epilepsy was as expected (rapid absorption and high variability). Staccato® alprazolam 2mg was well tolerated. Bodyweight had no clinically relevant effect on PK/safety variables."

Clinical • PK/PD data • CNS Disorders • Cough • Epilepsy • Respiratory Diseases

Pharmacokinetics of Staccato® alprazolam in healthy adult participants in two phase 1 studies: An open-label smoker study and a randomized, placebo-controlled ethnobridging study. (PubMed, Epilepsia) - P1 | "Alprazolam was rapidly absorbed, and therapeutic drug levels were achieved within 2 min postdose when administered to the lung with the Staccato device. Staccato alprazolam was generally well tolerated and displayed a safety profile consistent with that known from other alprazolam applications. No new safety signals were identified."

Journal • P1 data • PK/PD data • Anesthesia • CNS Disorders • Epilepsy

Pharmacokinetics of Staccato® Alprazolam in Healthy Adult Participants: Phase 1, Randomized, Placebo-Controlled Ethno-Bridging Study (AES 2023) - P1 | "Alprazolam was very rapidly absorbed when administered with the Staccato® device, as demonstrated by a very short Tmax achieved within 2 min post-dose in most participants. High Cmax was observed in Japanese and Chinese participants. However, across the three ethnic groups alprazolam concentrations were similar by five to ten minutes post-dose, and there were no differences between the total exposure of alprazolam (as shown by AUCinf and AUC0-t) suggesting no need for dose adjustments."

Clinical • P1 data • PK/PD data • Anesthesia

Pharmacokinetics and Tolerability of Single-dose Staccato® Alprazolam in Adolescents with Epilepsy and Population PK Analysis to Support Dose Selection in Adolescents (AES 2023) - P1 | "Alprazolam PK following Staccato® administration in adolescents with epilepsy was as expected, with rapid absorption and high variability. Staccato® alprazolam 2mg was well tolerated. BW had no clinically relevant effect on PK/safety variables."

Clinical • PK/PD data • CNS Disorders • Cough • Epilepsy • Respiratory Diseases

Pulmonary Safety of Staccato® Alprazolam in Healthy Participants and Participants with Mild Asthma: Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial (AES 2023) - P1 | "Two doses of Staccato® alprazolam (either 1mg or 2mg) administered 72 hours apart were well tolerated in healthy participants and those with mild asthma. Minor decreases in FEV1 from baseline were observed with Staccato® alprazolam vs placebo at several timepoints; however these were not considered clinically relevant. No evidence of clinically relevant airway obstruction related to Staccato® alprazolam was observed in healthy participants and those with mild asthma."

Clinical • P1 data • Asthma • Cough • Dysphonia • Immunology • Pulmonary Disease • Respiratory Diseases

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. (PubMed, CNS Drugs) - "The first group consists of positive allosteric modulators of GABA receptors and includes Staccato alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101...These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents..."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies

A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Jul 2023 ➔ Apr 2024 | Trial primary completion date: Jul 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

A Study to Test the Safety and Tolerability of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures (clinicaltrials.gov) - P3 | N=300 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | Trial completion date: Aug 2025 ➔ May 2026 | Trial primary completion date: Aug 2025 ➔ May 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

A Relative Bioavailability Study of Staccato Alprazolam Versus Oral Alprazolam in Healthy Study Participants (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: UCB Biopharma SRL | Recruiting ➔ Completed

Trial completion

A Relative Bioavailability Study of Staccato Alprazolam Versus Oral Alprazolam in Healthy Study Participants (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Recruiting

Enrollment open

A Relative Bioavailability Study of Staccato Alprazolam Versus Oral Alprazolam in Healthy Study Participants (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: UCB Biopharma SRL

New P1 trial

A randomized Phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination. (PubMed, Epilepsia) - P2 | "Both 1.0 mg and 2.0 mg doses of Staccato® alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato® alprazolam for rapid cessation of seizures in an outpatient setting."

Journal • P2b data • CNS Disorders • Cough • Epilepsy • Respiratory Diseases

A study to assess the pharmacokinetics and safety of Staccato alprazolam in adolescent study participants with epilepsy (clinicaltrialsregister.eu) - P1 | N=14 | Sponsor: UCB Biopharma SRL

New P1 trial • CNS Disorders • Epilepsy

A Study to Assess the Pharmacokinetics (PK) and Safety of Staccato Alprazolam in Adolescent Study Participants With Epilepsy (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: UCB Biopharma SRL | Recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

Epilepsy: Expert opinion on emerging drugs in phase 2/3 clinical trials. (PubMed, Expert Opin Emerg Drugs) - "Novel mechanisms of action involve cholesterol degradation, mitochondrial pathways, anti-inflammation and neuro-regeneration. Earlier identification of genetic conditions through genetic testing will allow for earlier use of disease specific and disease-modifying therapies."

Journal • P2/3 data • CNS Disorders • Epilepsy • Immunology • Inflammation