Amyloid Cardiomyopathy, Transthyretin-Related
Conditions
Brief summary
This is a single center, prospective, randomized, placebo-controlled study of AG10 in healthy adult subjects
Detailed description
Up to 48 healthy volunteers will be given a single dose of AG10 or placebo and be monitored for safety and tolerability over a 5-day period. Up to 48 healthy volunteers will be given multiple doses of AG10 or placebo and be monitored for safety and tolerability over a 15-day period.
Interventions
DRUGAG10 oral tablet
Active single ascending dose
DRUGPlacebo Oral Tablet
Placebo single dose
Sponsors
Celerion
Eidos Therapeutics, a BridgeBio company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Subjects will be randomized with an overall ratio of 3:1 to AG10: placebo within each cohort
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Weight between \>50 kg and ≤110 kg; * BMI of 18 to 32 kg/m2; * Subjects who are healthy as determined by medical history, physical examination, 12 lead ECG and standard laboratory tests; * Subjects who are negative for drugs of abuse and alcohol tests; * Subjects who are non-smokers;
Exclusion criteria
* Subjects who have used prescription drugs within 4 weeks of first dosing; * Subjects who have a prior cholecystectomy; * Subjects who have used any over-the-counter medications within 7 days prior to Day -1; * Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue diseases or disorders; * Subjects who have an abnormal screening ECG;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety & tolerability: individual and summary blood pressures, heart rate, ECG and lab data presented in tabular form with descriptive statistics. Adverse events will be tabulated and summarized by Part A (SAD) vs. B (MAD), and treatment. | 30 days | To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Assessments: T1/2 | 30 days | Plasma half-life (t1/2) |
| Pharmacokinetic Assessments: Tmax | 30 days | Time to maximum concentration (Tmax) |
| Pharmacokinetic Assessments: Cmax | 30 days | Maximum concentration (Cmax) |
| Pharmacokinetic Assessments: Cmin | 30 days | Cmin |
| Pharmacokinetic Assessments: AUC | 30 days | Area under the plasma concentration-time curve (AUC) |
| Pharmacokinetic Assessments: Clearance | 30 days | Apparent clearance (CL/F) |
| Pharmacodynamic Assessments: Assessments of TTR stabilization will be listed and summarized by part, treatment, and time point using appropriate descriptive statistics. | 30 days | AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays, including Fluorescent Polarization Exclusion Assay (FPE) and Immunoblotting (Western Blot) and quantitation of prealbumin (TTR). |
| Pharmacodynamic Assessments: Western blot | 30 days | AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot) |
| Pharmacodynamic Assessments: prealbumin | 30 days | AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR). |
| Food effect: AUC | 30 days | To evaluate the effect of food on the PK of AG10. The log transformed values of total AUC will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect. |
| Food effect: Cmax | 30 days | To evaluate the effect of food on the PK of AG10. The log transformed values of Cmax will be analyzed using a linear mixed effect model with formulation, period, sequence, and carryover as fixed effects and subject as a random effect. |
| Pharmacokinetic Assessments: volume of distribution | 30 days | Apparent volume of distribution (Vss/F) |
Countries
United States
Outcome results
None listed