Single and Multiple Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of AG10

Study Overview
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Brief Summary
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This is a single center, prospective, randomized, placebo-controlled study of AG10 in healthy adult subjects

Detailed Description
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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.

Official Title
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A Phase 1 Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study of the Tolerability, Pharmacokinetics and Pharmacodynamics of AG10 in Healthy Subjects

Conditions
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Amyloid Cardiomyopathy, Transthyretin-Related

Intervention / Treatment
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* Drug: AG10 oral tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AG10 single oral dose<br>AG10 oral tablet, administered by mouth, once | Drug: AG10 oral tablet<br>* Active single ascending dose<br>* Other names: Eidos Therapeutics AG10;|
| Placebo Comparator: Placebo single oral dose<br>Placebo Oral Tablet, administered by mouth, once | Drug: Placebo Oral Tablet<br>* Placebo single dose<br>* Other names: Matching placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessments: T1/2 | Plasma half-life (t1/2) | 30 days | 
| Pharmacokinetic Assessments: Tmax | Time to maximum concentration (Tmax) | 30 days | 
| Pharmacokinetic Assessments: Cmax | Maximum concentration (Cmax) | 30 days | 
| Pharmacokinetic Assessments: Cmin | Cmin | 30 days | 
| Pharmacokinetic Assessments: AUC | Area under the plasma concentration-time curve (AUC) | 30 days | 
| Pharmacokinetic Assessments: Clearance | Apparent clearance (CL/F) | 30 days | 
| Pharmacokinetic Assessments: volume of distribution | Apparent volume of distribution (Vss/F) | 30 days | 
| Pharmacodynamic Assessments: Assessments of TTR stabilization will be listed and summarized by part, treatment, and time point using appropriate descriptive statistics. | 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). | 30 days | 
| Pharmacodynamic Assessments: Western blot | AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot) | 30 days | 
| Pharmacodynamic Assessments: prealbumin | AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR). | 30 days | 
| Food effect: AUC | 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. | 30 days | 
| Food effect: Cmax | 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. | 30 days |