Chronic Liver Disease, NASH - Nonalcoholic Steatohepatitis
Conditions
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.
Interventions
DRUGBLD-0409
For each cohort in both study parts, 8 subjects will be randomized in a 6:2 ratio to active (BLD-0409) : control (matched placebo). Study drug will be administered orally once a day, with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s).
DRUGControl: Placebo
Subjects will be randomized in a 6:2 ratio to control (matched placebo). Study drug will be administered orally once a with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s).
Sponsors
Blade Therapeutics
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
Subjects are eligible to be included in the study only if all the following criteria apply: Age and Gender 1. Male and female subjects 18-55 years of age (inclusive) at the time of signing the PICF. Diagnosis and disease characteristics 2. Subjects must be in good general health, in the opinion of the Investigator, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening, and/or before administration of the initial dose of study drug. 3. Subjects must have clinical laboratory values within normal ranges or \< 1.2 times upper limit of normal (ULN) as specified by the testing laboratory, unless deemed not clinically significant (NCS) by the Investigator, with exception of liver function tests which cannot be above the ULN. 4. Body mass index (BMI) 18 to ≤ 32 kg/m2. Reproductive Considerations Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For details refer to Appendix 4. 5. Female subjects and female partners of male subjects must use double barrier contraception and refrain from oocyte donation from first dose of study drug and for 60 days after last dose of study drug. Estrogen-containing products are not allowed. 6. Male subjects must agree to use highly effective, double barrier contraception and refrain from sperm donation from first dose of study drug and for 90 days after last dose of study drug. 7. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. Females not of childbearing potential must be surgically infertile or post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) level \> 40 mIU/mL at Screening. Informed Consent 8. Subjects must provide signed informed consent prior to study entry and have the ability and willingness to attend and comply with the necessary visits at the study site.
Exclusion criteria
Subjects meeting ANY of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 subjects with treatment-related subjects changes in physical examinations | up 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 treatment subjects with treatment-related changes in heart rate | up 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 treatment subjects with treatment-related changes in systolic & diastolic blood pressure | up 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 treatment subjects with treatment-related changes in body temperature | up 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 ECG tracings | up 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. |
| Number of subjects with treatment-related changes in QTc intervals | up 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 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 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 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 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
| Measure | Time frame | Description |
|---|---|---|
| Renal clearance (CLr) for each collection interval and over the entire period of sample collection | 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. |
| 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 |
| Any observed Changes in serum Lysophosphatidic Acid Receptor (LPA) C18:2 | up to 56 days | Measured by serum 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. |
| 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. |
| 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. |
| Apparent oral clearance | 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 volume of distribution | 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. |
| 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 collection | 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. |
| Percentage of dose excreted unchanged during each collection interval (Fe(t' t)) and over the entire period of sample collection | 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. |
Countries
Australia
Outcome results
None listed