SAD and MAD of Inhaled AR-501 in Health Adults and P. Aeruginosa Infected Cystic Fibrosis Subjects
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: Inhaled AR-501Drug: Inhaled Placebo
- Registration Number
- NCT03669614
- Lead Sponsor
- Aridis Pharmaceuticals, Inc.
- Brief Summary
This is a Phase 1/2a randomized, double-blind, two-part, dose-ascending, multicenter study of AR-501 (gallium citrate) solution, administered via inhalation, in healthy adult and P. aeruginosa infected cystic fibrosis (CF) subjects. Phase 1 of the study in HV subjects will consist of a single-ascending-dose (SAD) cohort, followed by the HV multiple-ascending-dose (MAD) cohort. Phase 2a of the study in CF subjects will consist of a MAD study design. The study will evaluate the safety and pharmacokinetic (PK) profile of single and repeat administrations of inhaled AR-501 solution in healthy adults, and the safety, PK and efficacy of repeat administrations of inhaled AR-501 solution in P. aeruginosa infected CF subjects.
- Detailed Description
Three dose levels (low, medium and high) will be assessed in succession, first in healthy volunteer (HV) subjects, then four ascending doses will be assessed in cystic fibrosis (CF) subjects. The study will be performed in 2 parts: Phase 1 part of the study in HV subjects will consist of a single-ascending-dose (SAD) cohort, followed by the HV multiple-ascending-dose (MAD) cohort. Phase 2a part of the study in CF subjects will consist of a MAD study design.
The HV cohort will include up to 48 subjects. The CF cohort will have 54 subjects. Thus, the total number of subjects is 102.
The Phase 1 HV study will be performed at a Phase 1 Clinical Study Unit and the Phase 2a will be performed at approximately 24 clinical trial sites located in the United States and possibly in Europe, some of which may be part of the Cystic Fibrosis Foundation (CFF)-accredited Therapeutic Development Network (TDN) or the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN). Subjects who meet all eligibility criteria, including giving informed consent, will be enrolled and undergo a screening period of 28 days for HV cohorts and 42 days for CF Cohorts.
The HV cohort will include up to 24 adult subjects in 3 dose groups (8 per dose group \[Low, Medium and High\]) for the SAD phase of the study. In each dose group, subjects will be randomly assigned in a 3:1 ratio to the active drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving inhaled placebo in a double-blind manner. The HV MAD phase of the study will include 24 adult subjects in 3 dose groups (8 per dose group \[Low, Medium and High\]). In each dose group, subjects will be randomly assigned in a 3:1 ratio to active study drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving inhaled placebo in a double-blind manner. All subjects in HV MAD cohorts will receive once weekly inhaled study drug (either AR-501 or matching placebo) for 4 weeks for a total of 5 doses.
The CF MAD cohort will evaluate 4 different dose levels for a total of 54 adult CF. Of the 54 subjects, 40 will be randomized to receive one of the three ascending doses of AR-501, while 14 will be randomized to receive placebo. All subjects in CF cohorts will receive once weekly inhaled study drug (either AR-501 or matching placebo) for 2 weeks for a total of 3 doses.
The primary purpose of this study is to assess preliminary clinical safety of inhaled AR-501. The true frequency of AEs is unknown, and the sample size cannot be estimated accurately. For unknown AEs, the probabilities of observing at least 1 AE among 36 total healthy adult subjects and 40 adult CF subjects receiving any AR-501 dose are ≥ 80% if the true rate of such events are at least 4.4% and 4.8% respectively.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 102
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AR-501 inhaled Inhaled AR-501 Four doses (low, medium, high, top) of inhaled AR-501 will be used. inhaled AR-501 Placebo Inhaled Placebo Four doses (low, medium, high, top) of inhaled placebo will be used
- Primary Outcome Measures
Name Time Method Clinical safety profile (adverse events) - Single Ascending Dose 28 days following dose administration Evaluation of adverse events in HV subjects
Clinical safety profile (adverse events) - Multiple Ascending Dose up to 28 days after last dose administration Evaluation of adverse events in HV and CF subjects
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK) Profile - SAD t½ 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: half-life (t½)
Pharmacokinetics (PK) Profile - MAD λz up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: terminal elimination rate (λz)
Pharmacokinetics (PK) Profile - MAD t½ up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: half-life (t½)
Pharmacokinetics (PK) Profile - SAD Cmax 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: Observed maximum concentration (Cmax)
Pharmacokinetics (PK) Profile - MAD AUC0-inf up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: area under the time-concentration curve (AUC) from time zero to infinity (AUC0-inf)
Pharmacokinetics (PK) Profile - SAD Clp 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: plasma clearance (Clp)
Pharmacokinetics (PK) Profile - MAD Cmax up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: Observed maximum concentration (Cmax)
Pharmacokinetics (PK) Profile - MAD AUC0-last up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: area under the time-concentration curve (AUC) from time zero to the last dose (AUC0-last)
Pharmacokinetics (PK) Profile - MAD Clp up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: plasma clearance (Clp)
Pharmacokinetics (PK) Profile - MAD Tmax up to 28 days after last dose administration Pharmacokinetics Characteristics in Multiple Ascending Dose CF Subjects: time to reach maximum concentration (Tmax)
Pharmacokinetics (PK) Profile - SAD AUC0-inf 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: area under the time-concentration curve (AUC) from time zero to infinity (AUC0-inf)
Pharmacokinetics (PK) Profile - SAD Tmax 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: time to reach maximum concentration (Tmax)
Pharmacokinetics (PK) Profile - SAD AUC0-last 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: area under the time-concentration curve (AUC) from time zero to the last dose (AUC0-last)
Pharmacokinetics (PK) Profile - SAD λz 28 days following dose administration Pharmacokinetics Characteristics in Single Ascending Dose HV Subjects: terminal elimination rate (λz)
Trial Locations
- Locations (1)
Research Site
🇺🇸Spokane, Washington, United States