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

Phase 1

Completed

• Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
• Interventions: Drug: Placebo Oral Tablet; Drug: AG10 oral tablet

• Registration Number: NCT03294707
• Lead Sponsor: Eidos Therapeutics, a BridgeBio company

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.

Study Timeline

• Study Start: 2017-09-11
• Study First Submitted: 2017-09-18
• Study First Submitted QC: 2017-09-22
• Study First Posted: 2017-09-27
• Primary Completion: 2018-02-05
• Status Verified: 2018-05
• Study Completion: 2018-05-18
• Last Update Submitted: 2018-05-21
• Last Update Posted: 2018-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo single oral dose	Placebo Oral Tablet	Placebo Oral Tablet, administered by mouth, once
AG10 single oral dose	AG10 oral tablet	AG10 oral tablet, administered by mouth, once

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
Pharmacokinetic Assessments: Tmax	30 days	Time to maximum concentration (Tmax)
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.
Pharmacokinetic Assessments: Cmin	30 days	Cmin
Pharmacokinetic Assessments: T1/2	30 days	Plasma half-life (t1/2)
Pharmacokinetic Assessments: Cmax	30 days	Maximum concentration (Cmax)
Pharmacokinetic Assessments: AUC	30 days	Area under the plasma concentration-time curve (AUC)
Pharmacokinetic Assessments: Clearance	30 days	Apparent clearance (CL/F)
Pharmacokinetic Assessments: volume of distribution	30 days	Apparent volume of distribution (Vss/F)
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.
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).

Trial Locations

Locations (1)

Celerion; 🇺🇸 Tempe, Arizona, United States