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

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

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

Study Overview

• Status: Completed
• Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
• Intervention / Treatment: Drug: AG10 oral tablet; Drug: Placebo Oral Tablet

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 Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AG10 single oral dose; AG10 oral tablet, administered by mouth, once	Drug: AG10 oral tablet; Active single ascending dose; Other Names: Eidos Therapeutics AG10
Placebo Comparator: Placebo single oral dose; Placebo Oral Tablet, administered by mouth, once	Drug: Placebo Oral Tablet; Placebo single dose; Other Names: Matching placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eidos Therapeutics, a BridgeBio company
• Collaborators: Celerion

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2017
• Primary Completion (Actual): February 5, 2018
• Study Completion (Actual): May 18, 2018

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 27, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Dermatologic Agents; Keratolytic Agents; Coal Tar
• Other Study ID Numbers: AG10-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No