A Study to Assess the Pulmonary Safety of Staccato Alprazolam in Healthy Study Participants and in Study Participants With Mild Asthma

UCB

Status and phase

Completed

Phase 1

Conditions

Participants With Mild Asthma

Healthy Study Participants

Treatments

Drug: Alprazolam

Other: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT04802746

UP0099

Details and patient eligibility

About

The purpose of the study is to assess the pulmonary safety of Staccato alprazolam in healthy study participants and in and study participants with mild asthma

Enrollment

78 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Part A: Healthy study participants

Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form (ICF)
Participants are overtly healthy at Screening and on Day -1 of each Treatment Period as determined by medical evaluation including medical history and physical examination
Participant has a body weight of at least 45 kg (female) and 50 kg (male) and body mass index (BMI) within the range 18 to 35 kg/m^2 (inclusive)
Participants may be male or female A male participant must agree to use contraception during the Treatment Periods and for at least 7 days after the last dose of study treatment and must refrain from donating sperm during this period

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Treatment Periods and for at least 30 days after the last dose of study treatment

Participant is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol
Participant has normal spirometry at Screening as demonstrated by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥ 90% of predicted. In case of an out-of-range result, 1 repeat test will be allowed. If the readings are out-of-range again, the study participant will be excluded

Part B: Study participants with mild asthma

Participant must be 18 to 55 years of age inclusive, at the time of signing the ICF
Participant has a documented history of mild asthma diagnosed at least 6 months prior to the Screening Visit in accordance with the Global Initiative for Asthma (GINA) Guidelines 2020 and/or the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 Guidelines 2007. The diagnosis of mild asthma can be documented by various sources of medical information including, but not limited to, the participant's medical record, prescriptions of asthma treatments, and/or previous spirometry assessments (including FEV1 reversibility after short-acting beta2-agonist (SABA) administration)
Participant has been on a stable asthma drug regimen (as needed short-acting beta2-agonist (SABA)s or combination low dose inhaled corticosteroids (ICS)-formoterol and maintenance treatment with daily low dose ICS or daily leukotriene receptor antagonists) for at least 4 weeks before the Screening Visit
Participant has normal breathing sounds during normal tidal breathing on lung auscultation
Participant has a percent predicted forced expiratory volume in 1 second (ppFEV1) value at Screening ≥80%. Before performing spirometric assessments at Screening, a washout period of at least 6 hours is required after the last SABA intake and is extended to at least 18 hours after the last intake of the combination low dose ICS-formoterol. In case of an out-of-range result, 1 repeat test will be allowed. If the readings are out of range again, the study participant will be excluded

Exclusion criteria

Part A: Healthy study participants

Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study
Participant has had a positive test for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or clinical signs/symptoms consistent with coronavirus disease 2019 (COVID-19) such as fever, persistent cough, shortness of breath, fatigue, and loss or change to senses of smell or taste during the 4 weeks prior to Screening or Day -1 of the first Treatment Period.
Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or comparative drugs (and/or an investigational device) as stated in this protocol
Participant has a known hypersensitivity to albuterol or similar short-acting beta2-agonist (SABA) that may be used as rescue medication administered in response to potential bronchospasm
Participant has a history of acute narrow angle glaucoma, hydrocephalus, or Myasthenia gravis
Participant has received or intends to use any prescription or nonprescription medicines, including enzyme inhibitors or inducers, over the counter remedies, and herbal and dietary supplements (including St. John's Wort) up to 2 weeks or 5 half-lives of the respective drug (whichever is longer) before the first administration of IMP and during the clinical part of the study, unless required to treat an adverse event (AE). This does not include oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy or implants, patches, or intrauterine devices (IUDs)/intrauterine hormone-releasing systems (IUSs) delivering progesterone (for female study participants)
Participant has previously participated in this study or participant has previously been assigned to treatment in a study of the medication under investigation in this study
Participant has participated in another study of an IMP (and/or an investigational device) within the previous 30 days before Screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an IMP (and/or an investigational device)
Participant has a SpO2 measured by pulse oximetry <95% for >30 seconds at Screening and on day -1 of each Treatment Period. In case of an out-of-range result, 1 repeat test will be allowed. If the readings are out- of- range again, the study participant will be excluded
Participant has a history or current condition characterized by airway hyperresponsiveness (eg, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, obstructive sleep apnea, pneumothorax, etc) at Screening and on Day -1 of each Treatment Period
Participant has contraindications for spirometry at Screening and on Day -1 of each Treatment Period (eg, history of myocardial infarction within 1 week, systemic hypotension, severe hypertension, significant atrial/ventricular arrhythmia, uncompensated heart failure, uncontrolled pulmonary hypertension, acute cor pulmonale, clinically unstable pulmonary embolism, history of syncope related to forced expiration/cough, history of cerebral aneurism, brain surgery within 4 weeks, recent concussion with continuing symptoms, eye surgery within 1 week, sinus surgery or middle ear surgery or infection within 1 week, presence of pneumothorax, thoracic surgery within 4 weeks, abdominal surgery within 4 weeks, late-term pregnancy, active or suspected transmissible respiratory or systemic infection, including tuberculosis within 4 weeks, physical conditions predisposing to transmission of infections, such as hemoptysis, significant secretions or oral lesions or oral bleeding; acute illness 5 days before Screening, upper respiratory tract infection in the 4 weeks before Screening)

Part B: Study participants with mild asthma

Participant is taking a prohibited medication or has taken a prohibited medication as defined in the Protocol
Participant has a history of or current respiratory disease characterized by airway hyperresponsiveness excluding asthma (eg, COPD, pulmonary fibrosis, obstructive sleep apnea, pneumothorax, etc)

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

78 participants in 8 patient groups, including a placebo group

Sequence ABC in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato Placebo (A) and two fixed doses of Staccato alprazolam Dose 1 (B) and Staccato alprazolam Dose 2 (C) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Sequence BCA in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato alprazolam Dose 1 (B), Staccato alprazolam Dose 2 (C), and Staccato Placebo (A) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Sequence CAB in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato alprazolam Dose 2 (C), Staccato Placebo (A), and Staccato alprazolam Dose 1 (B) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Sequence ACB in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato Placebo (A), Staccato alprazolam Dose 2 (C), and Staccato alprazolam Dose 1 (B) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Sequence BAC in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato alprazolam Dose 1 (B), Staccato Placebo (A), and Staccato alprazolam Dose 2 (C) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Sequence CBA in Part A

Experimental group

Description:

Study participants randomized to this arm will receive Staccato alprazolam Dose 2 (C), Staccato alprazolam Dose 1 (B), and Staccato Placebo (A) at pre-specified time points during 3 separate Treatment Periods in Part A.

Treatment:

Other: Placebo

Drug: Alprazolam

Staccato alprazolam in Part B

Experimental group

Description:

Study participants randomized to this arm will receive Staccato alprazolam at pre-specified time points in Part B.

Treatment:

Drug: Alprazolam

Staccato placebo in Part B

Placebo Comparator group

Description: