Healthy Volunteers
Conditions
Keywords
AKB-9090, Single-centre, Single Ascending Dose, Multiple Ascending Dose, First-in-human, Safety, Tolerability, Randomized, Double-blind, Healthy Volunteers
Brief summary
This is a first-in-human (FIH study designed to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic effects of AKB-9090 in healthy adult participants. The study consists of two stages: Stage 1, a single ascending dose (SAD) phase with four dose cohorts, and Stage 2, a multiple ascending dose (MAD) phase with one dose cohort. Approximately 32 participants in SAD and 12 in MAD are planned to be enrolled.
Interventions
DRUGAKB-9090
AKB-9090 will be administered intravenously
OTHERPlacebo
Matching Placebo administered intravenously
Sponsors
Akebia Therapeutics
Emerald Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy adult participants with no clinically significant findings, as judged by the investigator, based on physical examination, 12-lead ECG, alcohol breath test, and clinical laboratory tests (including serum chemistry, hematology, coagulation, urine drug screen, and urinalysis). * Body mass index (BMI) greater than 18.5 and less than 32.0 kg/m\^2 at screening. * In the Investigator's opinion, willing and able to provide written informed consent and comply with the all protocol requirements, including required confinement, outpatient visits, and protocol-specified restrictions (including refraining from major lifestyle changes) from signature of the informed consent form (ICF) through the last study visit. Key
Exclusion criteria
* Clinically significant metabolic, hepatic, renal, hematologic, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatologic, urogenital, ophthalmologic, ear/nose/throat, psychiatric, or neurologic disorder. * History of active or recurrent malignancy within 2 years before screening or during the screening period, or currently receiving treatment or suppressive therapy for cancer, except for: 1. Treated basal cell carcinoma of the skin 2. Curatively resected squamous cell carcinoma of the skin 3. Treated colonic or cervical carcinoma in situ * Abnormal ECG findings at screening, including: 1. Severe bradycardia (heart rate \<40 beats per minute) on any measurement 2. Mean QT Interval Using Fridericia's Formula (QTcF) \>450 msec for males or \>470 msec for females * Elevated laboratory values (\>1.25 × upper limit of normal \[ULN\]) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine at the screening visit or at check-in. * Evidence of acute or chronic hepatitis B (positive hepatitis B surface antigen) or hepatitis C infection (positive hepatitis C antibody and positive hepatitis C ribonucleic acid \[RNA\] test). * Use of nicotine-containing products (including cigarettes, cigars, tobacco, gum, patches, vaping, and e-cigarettes), caffeine-containing foods or beverages, and alcohol-containing foods or beverages during study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants who will report serious Treatment emergent adverse events (TEAEs) and TEAEs | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Physical Examinations | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Vital Signs | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG) | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Chemistry parameters | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Hematology Parameters | from first dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Lipid Parameters | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Coagulation Parameters | From First Dose to Day 7 |
| Number of Participants with Clinically Significant Changes in Urinalysis Parameters | From First Dose to Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| Stage 1 SAD Cohorts: Maximum observed plasma concentration (Cmax) of AKB-9090 | At Day 1 |
| Stage 1 SAD Cohorts: Time of maximum plasma concentration (Tmax) of AKB-9090 | At Day 1 |
| Stage 1 SAD Cohorts: Area under concentration time curve (AUC) from time 0 to the last observation (AUClast) of AKB-9090 | At Day 1 |
| Stage 1 SAD Cohorts: Apparent body clearance (CL) of AKB-9090 | At Day 1 |
| Stage 1 SAD Cohorts: AUC from time 0 to infinity (AUCinf) of AKB-9090 | At Day 1 |
| Stage 1 SAD Cohorts: Terminal half-life (T1/2) of AKB-9090 | At Day 1 |
| Stage 2 MAD Cohorts: Cmax of AKB-9090 | At Day 1 and Day 7 |
| Stage 2 MAD Cohorts: Tmax of AKB-9090 | At Day 1 and Day 7 |
| Stage 2 MAD Cohorts: AUC to 24 hours post-dose (AUC24) of AKB-9090 | At Day 1 |
| Stage 2 MAD Cohorts: CL of AKB-9090 | At Day 1 and Day 7 |
| Stage 2 MAD Cohorts: T1/2 of AKB-9090 | At Day 1 and Day 7 |
| Stage 2 MAD Cohorts: AUC at Steady state (AUCss) of AKB-9090 | At Day 7 |
| Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Erythropoietin (EPO) | Baseline (Day 1) and at 6, 12, 18, and 24 hours post-dose |
| Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Red Blood Cell Count (RBC) | Baseline (Day 1) and At Days 2, 8, and 13 |
| Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count | Baseline (Day 1) and At Days 2, 8, and 13 |
| Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - EPO | Baseline (Day 1 and Day 7) and at 6, 12, 18, and 24 hours post-dose |
| Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - RBC | Baseline (Day 1) and At Days 4, 8, 14, and 21 |
| Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count | Baseline (Day 1) and At Days 4, 8, 14, and 21 |
Countries
New Zealand
Contacts
CONTACTDr. Leanne Barnett
STUDY_DIRECTORDr. Leanne Barnett, Leanne.barnett@nzcr.co.nz
New Zealand Clinical Research (NZCR)
Outcome results
None listed