Healthy, Healthy Smoker
Conditions
Brief summary
This is a 3-part, randomised, double-blind, placebo-controlled, first in human study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled RB042.
Detailed description
The purpose of this study is to measure the safety, tolerability, PK, and PD of inhaled RB042 compared with inhaled placebo in healthy adult volunteers and healthy adult smokers. Study details include: * Overall study duration of up to 14 months. * Participants in Part A (healthy adult volunteers) will be required to visit the study site for assessments on 11 occasions, including a 4-day in-house stay, over 4 months. * Participants in Parts B (healthy adult volunteers) and C (healthy adult smokers) will be required to visit the study site for assessments on 13 occasions, including a 17-day (Day -1 to 16) and 3-day (Day 21 to 24) in-house stay, over 5 months. * Participants will be administered a single dose (Part A) or multiple doses (Parts B and C) of study intervention.
Interventions
DRUGRB042
A single or multiple doses of RB042 will be administered via a nebuliser.
A single or multiple doses of placebo will be administered via a nebuliser.
Sponsors
RAGE Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Participants must be overtly healthy as determined by medical evaluation * Part C only: have a ≥10 pack years smoking history, have smoked tobacco products (cigarettes, cigars, or equivalent) regularly for the past 12 months, and currently smoke daily. * Have forced expiratory volume (FEV1) ≥80% predicted and FEV1 to FVC ratio (FEV1/FVC) ≥0.7 at Screening and on Day -1 * Body weight at least 50 kg and have a body mass index (BMI) within the range 18.0 and 32.0 kg/m2 (inclusive) * Women of childbearing potential (WOCBP) must have a negative pregnancy test and must not be lactating. * Participants must agree to use an approved method(s) of highly effective contraception as defined in the protocol.
Exclusion criteria
* Clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes. * Chronic or active respiratory disease (e.g., asthma, COPD) or history of angioedema within 3 years. * Active or chronic liver disease, or abnormal liver function tests (ALT, AST, or bilirubin outside reference range, except Gilbert's syndrome). * QTcF \>450 msec (males) or \>470 msec (females). * Renal impairment (creatinine clearance \<90 mL/min) or thrombocytopenia (\<150 × 10⁹/L). * Positive test for hepatitis B surface or core antigen, hepatitis C (unless HCV-RNA negative), or HIV. * Active respiratory infection within 5 days before study start. * Recent or concurrent use of medications, herbal supplements, vaccines, or blood products that could interfere with study safety or interpretation. * Participation in another investigational study within 30 days, or blood donation \>400 mL within 30 days. * Parts A and B only: Regular smoking (≥1 day per week) within 6 months prior to dosing, or a positive urine cotinine test at screening or Day -1. * Excessive alcohol consumption (\>21 drinks/week for males or \>14 for females). * History of severe drug reaction or anaphylaxis. * Contraindication to, or unwillingness to undergo, bronchoscopy. * Any psychiatric or medical condition that, in the investigator's opinion, could compromise safety or compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and frequency of treatment-emergent adverse events (TEAEs) | From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B) | To assess the safety and tolerability of single and multiple doses of RB042 when administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) | From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B) | To characterize the Cmax of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
| Time to maximum concentration (Tmax) | From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B) | To characterize the Tmax of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
| Terminal elimination half-life (t½) | From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B) | To characterize the t½ of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
| Area under the concentration-time curve (AUC) | From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B) | To characterize the AUC of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
| Trough concentration | On Days 7, 14, and 21 | To characterize the AUC of RB042 following multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers |
Countries
Australia
Contacts
CONTACTChief Medical Officer
Outcome results
None listed