Single-dose AQ001S PK Study in Healthy Volunteers

Pharmacokinetics Clinical Trial

— BORA  

Official title:

A Randomized, Open Label, Single-center, Single-dose, Four-period Crossover Clinical Trial to Assess the PK Profile and Safety of Budesonide Inhalation Solution AQ001S Compared to Budesonide Inhalation Suspension in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05148312
• Other study ID #: BORA Study
• Status: Completed
• Phase: Phase 1
• Start date: November 12, 2021
• Est. completion date: February 21, 2022

Study information

• Verified date: November 2021
• Source: Aquilon Pharmaceuticals S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. Three (3) different AQ001S concentrations (i.e. 0.125 mg/2 mL, 0.250 mg/2mL and 0.500 mg/2 mL) will be compared to budesonide inhalation suspension 1.0 mg/2 ml.

Twenty (20) male and female healthy volunteers, from 18 to 60 years old, must complete the study. The study drug will be administered by nebulization.

The primary PK objective is to characterize the pharmacokinetic (PK) profile of AQ001S inhalation solution.

The primary safety objective is to assess the safety of AQ001S inhalation solution.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 21, 2022
• Est. primary completion date: December 24, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Subjects who have given written informed consent.

2. Healthy volunteers of both genders, aged = 18 and = 60 years.

3. Subjects with body weight > 45 kg and Body Mass Index = 18.5 and = 24.9kg/m2.

4. 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%).

5. 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.

6. Subjects who never smoked.

7. 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).

8. Any female subject with childbearing potential has a negative pregnancy test at Screening visit and prior to dosing at each treatment period.

9. Reliable subjects who are willing to be available for the duration of the clinical study and willing to comply with clinical study procedures.

10. Subjects who have the ability to understand the requirements of the clinical study.

Exclusion Criteria:

1. Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history) or clinically relevant laboratory abnormalities.

2. Clinically significant history or presence of pulmonary malformations, chronic bronchitis, asthma, emphysema, cystic fibrosis or any other pulmonary disease

3. History or presence of pulmonary tuberculosis.

4. Viral or bacterial upper or lower respiratory tract infection, or sinus or middle ear infection, within 4 weeks prior to the screening visit.

5. Untreated oral candidiasis.

6. 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.

7. 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.

8. Eye disorders, especially glaucoma, or a family history of glaucoma.

9. History of alcohol or drug abuse.

10. Inability to abstain from alcohol consumption for the duration of study period.

11. Immunosuppressive treatment, including topical and systemic corticosteroids (e.g., oral, parenteral, ocular, nasal or inhaled), within 4 weeks before Screening Visit.

12. 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.

13. Pregnant or breastfeeding female subjects.

14. History of hypersensitivity or existing contraindication to budesonide or any other study medication ingredients.

15. Blood or plasma donation within 4 weeks prior to Screening Visit.

16. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the clinical study.

17. History or presence of any other clinically relevant disease of any major system organ class (e.g. cardiovascular, pulmonary, renal, hepatic, gastrointestinal, reproductive, endocrinological including any type of Diabetes mellitus, neurological, psychiatric or orthopedic disease) as judged by the Investigator.

18. COVID-19, Hepatitis B and C and HIV positive tests

19. Any COVID-19 vaccine within 2 weeks prior to the first dose of study drugs, and during the entire study participation including 2 weeks after the last dose of study drug.

20. Subjects who participated in an investigational study within the 12 weeks prior to the start of the study

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• Budesonide Inhalant Product
Single-dose of budesonide solution administered by nebulization.

Locations

Country	Name	City	State
Bulgaria	MC Comac Medical Ltd.	Sofia

Sponsors (1)

Lead Sponsor	Collaborator
Aquilon Pharmaceuticals S.A.

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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