Single-dose AQ001S PK Study in Healthy Volunteers

NCT05148312 | Completed Phase 1

• 1 other identifier: BORA Study
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open label, single-center, single-dose, four-period crossover clinical study to assess the pharmacokinetic profile and safety of a budesonide inhalation solution (AQ001S) compared to a budesonide inhalation suspension (comparator) in healthy volunteers.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (16)

• Assessment of pharmacokinetics (Cmax) of budesonide through analysis of blood samples

  Blood samples will be collected from each subject using an indwelling intravenous catheter. In total 17 blood samples for PK assessments over 24 hours will be collected.

  Day 1 (predose) and at 2', 5', 10', 15', 20', 30', 45', 60', 90', 120', 180', 240', 360', 10h, 18h and 24h postdose

• Assessment of pharmacokinetics (Tmax) of budesonide through analysis of blood samples

  Blood samples will be collected from each subject using an indwelling intravenous catheter. In total 17 blood samples for PK assessments over 24 hours will be collected.

  Day 1 (predose) and at 2', 5', 10', 15', 20', 30', 45', 60', 90', 120', 180', 240', 360', 10h, 18h and 24h postdose

• Assessment of pharmacokinetics (AUC) of budesonide through analysis of blood samples

  Blood samples will be collected from each subject using an indwelling intravenous catheter. In total 17 blood samples for PK assessments over 24 hours will be collected.

  Day 1 (predose) and at 2', 5', 10', 15', 20', 30', 45', 60', 90', 120', 180', 240', 360', 10h, 18h and 24h postdose

• Assessment of the safety through to incidence of Adverse Events of AQ001S inhalation solution

  Incidence of treatment-related adverse events (AE), including acute bronchospasm

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to vital signs (blood pressure: systolic and diastolic blood pressure) of AQ001S inhalation solution

  Vital signs assessment through blood pressure (systolic and diastolic blood pressure)

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to vital signs (pulse rate) of AQ001S inhalation solution

  Vital signs assessment through pulse rate

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to vital signs (respiratory rate) of AQ001S inhalation solution

  Vital signs assessment through respiratory rate

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to ECG (PR interval duration)

  ECG assessment through to PR interval duration

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to ECG (heart rhythm) of AQ001S inhalation solution

  ECG assessment through to heart rhythm

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to ECG (QRS interval duration) of AQ001S inhalation solution

  ECG assessment through to QRS interval duration

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to ECG (Corrected QT interval (QTc)) of AQ001S inhalation solution

  ECG assessment through to Corrected QT interval

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to ECG (QT interval duration) of AQ001S inhalation solution

  ECG assessment through to QT interval duration

  From baseline up to 17 days after first study drug intake

• Assessment of the general tolerability through to physical examination

  General tolerability through the rate of patients with observed abnormalities in the following organic systems: general appearance, head and neck (incl. oropharyngeal examination), skin, respiratory system, cardiovascular system, abdomen, urogenital system, nervous system, ear, eyes and nose, musculoskeletal system

  From baseline up to 17 days after first study drug intake

• Assessment of the local tolerability through to increased bronchial irritability of AQ001S inhalation solution

  Incidence of Increased bronchial irritability

  From baseline up to 17 days after first study drug intake

• Assessment of the local tolerability through to paradoxical bronchospasm of AQ001S inhalation solution

  Incidence of paradoxical bronchospasm

  From baseline up to 17 days after first study drug intake

• Assessment of the local tolerability through to oropharyngeal examination ((e.g. vocal cord myopathy, fungal infection) of AQ001S inhalation solution

  Incidence of oropharyngeal examination ((e.g. vocal cord myopathy, fungal infection)

  From baseline up to 17 days after first study drug intake

Study Arms (4)

AQ001S 0.125 mg/2mL single-dose

EXPERIMENTAL

AQ001S 0.125 mg/2 ml (budesonide 0.125 mg/2 ml inhalation solution) single-dose administered by nebulization.

Drug: Budesonide Inhalant Product

AQ001S 0.250 mg/2mL single-dose

EXPERIMENTAL

AQ001S 0.250 mg/2 ml (budesonide 0.250 mg/2 ml inhalation solution) single-dose administered by nebulization.

Drug: Budesonide Inhalant Product

AQ001S 0.500 mg/2mL single-dose

EXPERIMENTAL

AQ001S 0.500 mg/2 ml (budesonide 0.500 mg/2 ml inhalation solution) single-dose administered by nebulization.

Drug: Budesonide Inhalant Product

Budesonide inhalation suspension 1.0 mg/2 ml single-dose

ACTIVE COMPARATOR

Pulmicort Respules® 1.0 mg/2 ml is a budesonide inhalation suspension administered by nebulization.

Drug: Budesonide Inhalant Product

Interventions

Budesonide Inhalant Product DRUG

Single-dose of budesonide solution administered by nebulization.

Also known as: Budesonide solution administered by nebulization

AQ001S 0.125 mg/2mL single-dose; AQ001S 0.250 mg/2mL single-dose; AQ001S 0.500 mg/2mL single-dose; Budesonide inhalation suspension 1.0 mg/2 ml single-dose

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who have given written informed consent.
• Healthy volunteers of both genders, aged ≥ 18 and ≤ 60 years.
• Subjects with body weight \> 45 kg and Body Mass Index ≥ 18.5 and ≤ 24.9kg/m2.
• Healthy volunteers are declared healthy based on medical history, physical examination, electrocardiogram, pulmonary function test (Forced Expiratory Volume in 1 second ≥ 80% of the predicted normal value and Forced Expiratory Volume in 1 second/ Forced Vital Capacity ≥ 70%).
• Clinical laboratory values within the laboratory stated normal range; if not within this range, they must be without any clinical significance according to the Investigator.
• Subjects who never smoked.
• Women of childbearing potential (WOCBP) may be enrolled if they practice a method of birth control with a reliability of at least 90% and agree to continue doing so throughout the treatment period (e.g. condom, intrauterine device or hormonal contraception).
• Any female subject with childbearing potential has a negative pregnancy test at Screening visit and prior to dosing at each treatment period.
• Reliable subjects who are willing to be available for the duration of the clinical study and willing to comply with clinical study procedures.
• Subjects who have the ability to understand the requirements of the clinical study.

You may not qualify if:

• Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history) or clinically relevant laboratory abnormalities.
• Clinically significant history or presence of pulmonary malformations, chronic bronchitis, asthma, emphysema, cystic fibrosis or any other pulmonary disease
• History or presence of pulmonary tuberculosis.
• Viral or bacterial upper or lower respiratory tract infection, or sinus or middle ear infection, within 4 weeks prior to the screening visit.
• Untreated oral candidiasis.
• History or presence of prolonged QTc interval (\> 450 ms), or any other clinically significant electrocardiogram abnormalities as judged by the Investigator based on 12-lead electrocardiogram recordings at Screening Visit.
• History or presence of malignancy of any system organ class (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years prior to Screening Visit, regardless of whether there is no evidence of local recurrence or metastases.
• Eye disorders, especially glaucoma, or a family history of glaucoma.
• History of alcohol or drug abuse.
• Inability to abstain from alcohol consumption for the duration of study period.
• Immunosuppressive treatment, including topical and systemic corticosteroids (e.g., oral, parenteral, ocular, nasal or inhaled), within 4 weeks before Screening Visit.
• Use of prescription or non-prescription drugs, except for simple analgesics (e.g. paracetamol) and hormonal contraception for women, including vitamins, herbal and dietary supplements (including St John's Wort \[Hypericum\]) within 7 days (or 2 weeks if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the Screening Visit.
• Pregnant or breastfeeding female subjects.
• History of hypersensitivity or existing contraindication to budesonide or any other study medication ingredients.
• Blood or plasma donation within 4 weeks prior to Screening Visit.

Sponsors & Collaborators

• Aquilon Pharmaceuticals S.A.: lead

Study Sites (1)

MC Comac Medical Ltd.

Sofia, 1612, Bulgaria

Location

Study Officials

• Dobrin Svinarov, MD

  MC Comac Medical Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study drug will be administered by nebulization. The subjects will adhere to the following therapeutic scheme at each treatment period of 3 days, for 4 treatment periods: * One single dose of study medication on the first day of the treatment period, followed by * Minimum washout period of 3 days, i.e. minimum 72 hours between two drug administrations The pharmacokinetics profile of budesonide in plasma, will be evaluated through pharmacokinetics parameters, calculated for each single dose, and based on 17 timepoints from 0 to 24h.

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: December 8, 2021
• Study Start: November 12, 2021
• Primary Completion: December 24, 2021
• Study Completion: February 21, 2022
• Last Updated: November 3, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Beginning 6 months and ending 5 years following article publication.
• Access Criteria: To Investigators whose proposed use of the data has been approved by sponsor.

Locations

BU (1)