A Phase 1, Randomized, Blinded, Placebo-Controlled, First-in-Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of APR002 Administered by Inhalation in Healthy Volunteers
- Conditions
- COVID-19Respiratory - Other respiratory disorders / diseasesInfection - Other infectious diseases
- Registration Number
- ACTRN12622001572752
- Lead Sponsor
- Avance Clinical Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 42
1. The participant is a healthy adult male or female. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease following a detailed medical history (specific attention to prior asthma or AR); a complete physical examination; vital signs; blood sampling of hematology, chemistry, and virology; urinalysis, and urine drug testing. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy participants.
2. The participant is aged 18 to 55 years, inclusive at the time of consent.
3. The participant weighs at least 45 kg (99 lb) and has a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive at Screening.
4. A male participant who is nonsterilized and sexually active with a female partner of
childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days after the dose of study drug.
5. A female participant of childbearing potential* who is sexually active with a nonsterilized male partner agrees to use adequate contraception from the time of signing the informed consent, throughout the duration of the study, and for 30 days after the dose of study drug.
*Females of non-childbearing potential may be enrolled. Female participants of childbearing potential must follow protocol specified contraception guidance.
6. Continuous non-smoker who has not used tobacco/nicotine-containing products for at
least 3 months prior to the first dosing based on participant self-reporting.
7. Medically healthy (i.e., with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee), including according to the following:
- Seated blood pressure is greater than or equal to 90/50 mmHg and less than or equal to 140/90 mmHg at the Screening Visit and check-in at rest for 5 minutes.
- Seated heart rate/pulse is greater than or equal to 40 bpm and less than or equal to 99 bpm at the Screening Visit and
check-in at rest for 5 minutes. Heart rate/pulse below 50 bpm to be discussed with the Medical Monitor before study inclusion.
- QTcF intervals are less than or equal to 470 msec (females) / less than or equal to 450 msec (males) at the Screening
Visit and check-in.
- Estimated creatinine clearance is greater than or equal to 80 mL/min at the Screening Visit, calculated utilizing the Cockcroft & Gault formula.
- ALT and AST are less than or equal to upper limit of normal (ULN) at the Screening Visit and check-in, if ALT/AST is less than or equal to 1.5 × ULN, discussion between the Sponsor and Investigator must occur before inclusion.
- Total bilirubin is less than or equal to 1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%) at the Screening Visit and check-in.
1. Is mentally or legally incapacitated or has significant emotional problems at the time of the Screening Visit or expected during the conduct of the study.
2. History or presence of clinically significant medical (e.g., chronic obstructive pulmonary disease, asthma, COVID-19, etc.) or psychiatric condition or disease in the opinion of the Investigator or designee. For example, pulmonary function test results should
be within normal range, FEV1 % Predicted: 80 to 120%, FVC % Predicted: 80 to 120%, FEV1/FVC % Predicted: 85 to 110%.
3. History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
4. History of unexplained syncope.
5. History or presence of acute porphyria at the Screening Visit.
6. Lymphoma, leukemia, or any malignancy within the past 5 years of the Screening Visit except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years or breast cancer within the past
10 years of the Screening Visit.
7. Clinically significant cardiac disease (e.g., myocardial infarction, stroke, unstable angina, claudication) within 6 months prior to check-in.
8. History of clinically significant hepatic impairment.
9. Current or chronic history of liver disease, including but not limited to hepatitis virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, ?-1 antitrypsin deficiency, primary biliary
cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the Investigator.
10. Known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
11. Participant has had previous episodes of seizures or convulsion (lifetime), including absence seizure and febrile convulsion.
12. Participant or any immediate family member has a history of epilepsy (including febrile convulsions).
13. Participant has a history of clinically significant neurological abnormalities including known abnormal electroencephalography at screening or brain injury including traumatic injury, perinatal cerebropathy and postnatal brain damage, blood-brain barrier abnormality, and angioma cavernous.
14. Participant has a history of cerebral arteriosclerosis.
15. Participant has a condition that can potentially reduce drug clearance (e.g., renal or hepatic insufficiency).
16. Clinically significant acute illness or infection within 14 days prior to check-in.
17. Major surgical procedure within 3 months prior to check-in.
18. History or known presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
19. History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
20. Positive urine drug or breath alcohol results at the Screening Visit or check-in.
21. Drinks alcohol in excess of 14 glasses/units per week, with 1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine. The participant has history of alcoholism, alcohol abuse (a current alcohol consumption of more than 2 drinks per day [a drink is defined as 5 oz (~150 mL) of wine, 12 oz (~355 mL) of beer, or 1 oz (~30 mL) of hard liquor]).
22. Current smoker or a history of smoking within 3 months of screenin
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method