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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BLD-0409 in Healthy Subjects

Phase 1
Completed
Conditions
Chronic Liver Disease
NASH - Nonalcoholic Steatohepatitis
Interventions
Registration Number
NCT04146805
Lead Sponsor
Blade Therapeutics
Brief Summary

A Phase 1a, Double Blind, Placebo-Controlled, Single-Center, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability Pharmacokinetics, and Pharmacodynamics of BLD-0409 in Healthy Volunteers

Detailed Description

The study will evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses (SAD) and multiple ascending doses (MAD) of BLD-0409 in healthy volunteers (HV) to facilitate the dose/dosing regimen selection for future clinical studies with BLD-0409 in various chronic liver diseases.

The study consists of two parts:

Part 1: SAD in HV with up to 6 cohorts (including a food effect cohort). For SAD cohorts and planned dosing schedule.

Part 2: MAD over 14 days with up to 6 cohorts. For MAD cohorts and planned dosing schedule.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1SAD/Part 2 MAD:Active Treatment(BLD-0409)BLD-0409For each cohort in both study parts, 6 subjects will be randomized to active (BLD-0409). Study drug will be administered orally once a day, with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s)
Primary Outcome Measures
NameTimeMethod
Number of treatment subjects with treatment-related changes in heart rateup to 56 days

Assessed by collecting and evaluating any observed changes in heart rate. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in hematology clinical laboratory test results.up to 56 days

Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

Number of treatment subjects with treatment-related changes in systolic & diastolic blood pressureup to 56 days

Assessed by collecting and evaluating any observed changes in systolic \& diastolic blod pressure. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in ECG tracingsup to 56 days

Assessed by performing 12-lead ECGs, and evaluating ECG tracings from baseline, by dose. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Incidence of Adverse Events (AEs)up to 56 days

AEs will be assessed by determining the incidence, severity, and dose relationship of adverse events

Number of treatment subjects with treatment-related changes in body temperatureup to 56 days

Assessed by collecting body temperature using a thermometer. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in urinalysis clinical laboratory test results.up to 56 days

Assessed by collecting and analyzing subjects' urine from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

Number of subjects with treatment-related subjects changes in physical examinationsup to 56 days

Assessed by performing physical examinations include general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes, from baseline by dose, through out the study.

Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in QTc intervalsup to 56 days

Assessed by performing 12-lead ECGs, and evaluating QTc intervals from baseline, by dose. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in chemistry clinical laboratory test results.up to 56 days

Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

Number of subjects with treatment-related changes in serology clinical laboratory test results.up to 56 days

Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

Secondary Outcome Measures
NameTimeMethod
Area under the drug concentration-time curve from time zero to the last measurable concentration (AUClast)up to 56 days

To characterize the Plasma pharmacokinetics(PK) of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo

Area under the drug concentration time curve from time 0 to infinity (AUC0-inf)up to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Time of the maximum drug concentration (tmax)up to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Apparent terminal elimination rate constant (kel)up to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Apparent elimination half life (t½)up to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Any observed Changes in serum Lysophosphatidic Acid Receptor (LPA) C18:2up to 56 days

Measured by serum in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Apparent oral clearanceup to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Apparent terminal volume of distributionup to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Amount excreted during each collection interval (Ae(t'-t''))up to 56 days

To characterize the urine PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Total amount of drug excreted unchanged in the urine over the entire period of sample collectionup to 56 days

To characterize the urine PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Percentage of dose excreted unchanged during each collection interval (Fe(t' t")) and over the entire period of sample collectionup to 56 days

To characterize the urine PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Maximum observed drug concentration (Cmax)up to 56 days

To characterize the Plasma PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Renal clearance (CLr) for each collection interval and over the entire period of sample collectionup to 56 days

To characterize the urine PK of BLD-0409 in healthy volunteers. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

Trial Locations

Locations (1)

Scientia Clinical Research

🇦🇺

Randwick, New South Wales, Australia

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