Healthy Volunteers
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetic characteristics of ICF001 following inhaled administration of single and multiple ascending doses in healthy participants.
Detailed description
This study will consist of 2 parts: a single ascending dose (SAD) study and a multiple ascending dose (MAD) study in healthy participants.
Interventions
DRUGICF001
ICF001 capsule-based inhalation powders.
DRUGPlacebo
Matching-placebo capsule-based inhalation powders.
Sponsors
VIVID CLINICAL SERVICES PTY LTD
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Understand the study procedures and methods, voluntarily participate in this study, and provide written informed consent. * Healthy adult participants aged 18 to 55 years (inclusive), both genders. * Body Mass Index (BMI) equal to (=) weight/height squared kilogram per meter square (kg/m\^2)): 18 less than or equal to (\<=) BMI \<=32; male weight greater than or equal to (\>=) 50.0 kilogram (kg) and less than (\<) 100.0 kg, female weight \>=45.0 kg and \<100.0 kg. * Confirmed to have no clinically significant abnormalities through physical examination, laboratory tests, vital signs assessment, and electrocardiogram (ECG), and determined by the investigator to be medically healthy. * Participants whose peak inspiratory flow rate measured by In-Check\^TM DIAL G16 is between 30 to 60 liters per minute (L/min) and whose total inspiratory duration exceeds 2 seconds. * Participants must be able to correctly and effectively use the inhaler device during the screening period and throughout the study. * Sexually active female participants of childbearing potential must agree to use effective contraception from screening until 35 days after the last dose and must not become pregnant or donate eggs during this period; Sexually active male participants with partners of childbearing potential must agree to use effective contraception from the first dose until 95 days after the last dose and must not donate sperm during this time; their fertile male or female partners must also agree to use effective contraception during this period. * Ability to successfully complete test dosing procedure following inhalation training on Day-1. * Able to understand the study procedures and provide signed informed consent to participate in the study.
Exclusion criteria
* Participants with a history of any clinically significant disease (including both past and current medical conditions), including but not limited to respiratory, cardiovascular, neurological, gastrointestinal, hematologic, endocrine, immune, dermatologic, malignancy, neuropsychiatric, ophthalmologic, or metabolic disorders, or any other condition that, in the opinion of the investigator (or designee), would make the participant unsuitable for participation in the study. A history of bariatric surgery or prior cholecystectomy; a history of eczema (provided no use of topical or systemic steroid treatments within 3 months prior to screening); a history of gestational diabetes that has fully resolved; current or past attention deficit hyperactivity disorder (ADHD), anxiety, or depression (provided no use of antidepressant medication within 6 months prior to screening); and Gilbert's syndrome are not considered exclusionary, provided they are not currently clinically significant and are acceptable at the investigator's discretion. * Participants who have undergone any major surgery within 3 months, or any minor surgery within 1 months prior to dosing, or who plan to undergo surgery during the study, or who have undergone surgery that may significantly affect the pharmacokinetic (PK) or safety evaluation of the study drug. * Participants with clinically significant oral diseases that, in the investigator's judgment, may affect the study (e.g., oral candidiasis, oral ulcers, lesions of the oral mucosa, etc.). * Participants with clinically significant nasal diseases such as severe rhinitis, sinusitis, nose cavity and nose septum infections and lesions. * Risk of bleeding: History of bleeding disorders, active peptic ulcer, or history of gastrointestinal bleeding; abnormal platelet count, international normalized ratio (INR), or activated partial thromboplastin Time (APTT) during the screening period. * History of asthma, chronic obstructive pulmonary disease (COPD), or reactive airway disease, or pulmonary function test findings consistent with asthma or COPD. * History of orthostatic hypotension, unexplained syncope, or hypertension. * During screening or re-screening, participants with a systolic blood pressure of \<90 millimeters of mercury (mmHg) or a diastolic blood pressure of \<50 mmHg after sitting for 5 minutes. * During screening or re-screening, participants with a systolic blood pressure of greater than (\>) 140 mmHg or a diastolic blood pressure of \>90 mmHg after sitting for 5 minutes. * During screening or re-screening, participants with a heart rate of \>100 beats/minute after sitting for 5 minutes. * Participants with a fever (temperature \>37.5 degrees Celsius \[°C\]) or symptomatic respiratory infection within 1 month prior to dosing, or those with any infection requiring systemic antibiotics/antiviral medications within 3 months prior to screening, or those with a history of recurrent infections. * Positive for Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, and hepatitis C. * During screening/baseline visit, participants with alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), or total bilirubin \>=1.5 the upper limit of normal (ULN). * Screening/Baseline Visit: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) \<80 percentage (%) of predicted value, or FEV1/FVC \< 0.7, or an oxygen saturation (SpO₂) \<95%. Spirometry may be repeated at the same visit for a total of 3 tests if initial results are considered unacceptable due to poor effort or technical issues, with the best value recorded. * Participants who smoked (including vaping) within 3 months prior to dosing, or with positive cotinine test results. * Participants with potential risk of airway hyperreactivity, such as those with prolonged exposure to dust or harmful gases. * Participants with a history of heavy alcohol consumption within 3 months prior to screening, defined as \>14 alcohol units per week for males and \>10 alcohol units per week for females (where 1 standard unit =375 milliliter (mL) of mid-strength beer (3.5% alcohol/volume), 100 mL of wine (13.5% alcohol/volume), or 30 mL of spirits (40% alcohol/volume)), or with a positive breath alcohol test, or who are unable to abstain from alcohol during the study period. * Participants who have received any known moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes (for example; barbiturates, phenothiazines, cimetidine, carbamazepine) within the 30 days prior to the study, and for whom the investigator believes that these medications may affect the participant's safety or the validity of the study results. * Participants with a history of drug abuse within 3 months prior to screening, or those with a positive urine drug screen. * Participants who have participated in any clinical trials of drugs or medical devices within 5 half-lives or 3 months after the last dose/administration, whichever is longer, prior to screening. * Participants who have donated or lost \>=400 mL of blood within 30 days prior to dosing. * Participants with difficulty in intravenous blood collection or intolerance to venipuncture, or those with a history of vasovagal syncope. * Participants who have used any medication (including prescription drugs, over-the-counter drugs, vitamin supplements, or traditional medicines, especially anticoagulants, antiplatelet agents, non-steroidal anti-inflammatory drugs, vasodilators, or potent CYP2C8 inhibitors such as gemfibrozil and rifampin) or received any health supplements or vaccines within 7 days prior to dosing (or 5 half-lives of the drug, whichever is longer). * Participants who have consumed foods that may affect drug metabolism within 7 days prior to dosing (including grapefruit or grapefruit products, pitaya, mango, pomelo, etc.), or those with other dietary habits that the investigator believes may affect the absorption, distribution, metabolism, or excretion of the drug, or those who are unwilling to discontinue consuming the aforementioned foods during the study period. * Participants who have consumed any coffee or tea, as well as beverages and foods containing coffee or tea ingredients, within 48 hours prior to dosing, or those who are unwilling to discontinue consuming these foods during confinement, and within 24 hours before each follow-up visit. * Participants with special dietary requirements who cannot comply with a standard diet. * Participants with a known allergy to the study drug or any of its components. * Female participants who are pregnant or breastfeeding, or who have plans to become pregnant during the study period or within 2 months after the last dose. * Participants are deemed by the investigator to be unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | Vital signs included blood pressure, heart rate, respiratory rate, and body temperature. |
| Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | — |
| Number of Participants With Clinically Significant Change From Baseline in Local Tolerability Findings | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | Local tolerability includes observation of cough, wheezing, chest tightness, sore throat, choking cough, throat itching, and foreign object sensation in the throat. |
| Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Findings | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | Laboratory parameters included hematology, blood chemistry, urinalysis, coagulation tests. |
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | — |
| Number of Participants With Clinically Significant Change From Baseline in Pulmonary Function Test Abnormalities | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | — |
| Number of Participants With an Adverse Event (AE) | From start of the study up to follow up (up to 38 days [SAD] and 50 Days [MAD]) | An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. |
Secondary
| Measure | Time frame |
|---|---|
| MAD: Ratio of Area Under the Plasma Concentration-Time Curve (RAUC) Following the last Dose of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Maximum Observed Plasma Concentration (Cmax) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Time of the Maximum Measured Plasma Concentration (Tmax) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Area Under the Plasma Concentration-Time Curve from Zero to the Last Measurable Time Point (AUC0-t) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Area Under the Plasma Concentration-Time Curve from Zero to Infinity (AUC0-∞) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Terminal Elimination Half-life (t½) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD and MAD: Terminal Elimination Rate Constant (λz) of ICF001 and its Active Metabolite (IC001-R1) | SAD: Predose, 5,15,30 mins,1,1.5,2,4,6,8,10,12,24,36,48 hrs postdose; MAD: Day 1: predose, 5,15,30 mins,1,1.5, 2,4,6,8,10,12 hrs post first dose; Days 2-7: predose; Day 7: 5,15,30 mins,1,1.5, 2,4,6,8,10,12,24 hours (Day 8) and 48 hours (Day 9) postdose |
| SAD: Apparent Clearance (CL/F) of ICF001 Only | Predose, 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36, 48 hours postdose |
| SAD: Apparent Volume of Distribution (Vd/F) of ICF001 Only | Predose, 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36, 48 hours postdose |
| SAD: Mean Residence Time (MRT) of ICF001 and its Active Metabolite (IC001-R1) | Predose, 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36, 48 hours postdose |
| SAD: Area Under the Curve Extrapolated Percentage (AUC_%Extrap) of ICF001 and its Active Metabolite (IC001-R1) | Predose, 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36, 48 hours postdose |
| MAD: Area Under the Concentration-Time Curve from Zero to 12 Hours (AUC0-12) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Area Under the Plasma Concentration-Time Curve from Zero to the Last Measurable Time Point (AUC0-t) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Steady-state Average Concentration (Cavg,ss) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Maximum Plasma Concentration in Steady State (Cmax,ss) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Steady-state Trough Plasma Concentration (Ctrough,ss) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Time of the Maximum Measured Plasma Concentration Steady State (Tmax,ss) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-τ, ss) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Apparent Clearance at Steady State (CLss/F) of ICF001 Only | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Apparent Volume of Distribution at Steady State (Vdss/F) of ICF001 Only | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Accumulation Ratio (Rac) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Degree of Fluctuation (DF) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| Steady-State Plasma Concentration Fluctuation (Swing) of ICF001 and its Active Metabolite IC001-R1 | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
| MAD: Ratio of Maximum Plasma Concentration (RCmax) of ICF001 and its Active Metabolite (IC001-R1) | Day 1: predose, 5, 15, 30 mins,1,1.5, 2, 4, 6, 8, 10,12 hrs post first dose; Days 2-7: predose; Day 7: 5, 15, 30 mins,1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours (Day 8) and 48 hours (Day 9) postdose |
Countries
Australia
Contacts
STUDY_DIRECTORJian Wang
VIVID CLINICAL SERVICES PTY LTD
Outcome results
None listed