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

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

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=250 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • 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; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Epilepsy • MRI

A study to test the safety and tolerability of Staccato alprazolam in study participants 12 years of age and older with epilepsy Vizsgálat a Staccato alprazolam biztonságosságának és tolerálhatóságának tesztelésére 12 éves és idősebb epilepsziában szenvedő vizsgálati résztvevőknél (clinicaltrialsregister.eu) - P3; N=300; Ongoing; Sponsor: UCB Biopharma SRL

Clinical • New P3 trial • CNS Disorders • Epilepsy