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

Amyloid Cardiomyopathy, Transthyretin-Related Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03294707
• Other study ID #: AG10-001
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2017
• Est. completion date: May 18, 2018

Study information

• Verified date: May 2018
• Source: Eidos Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: May 18, 2018
• Est. primary completion date: February 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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;

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy, Transthyretin-Related
• Cardiomyopathies

Intervention

Drug:
• AG10 oral tablet
Active single ascending dose
• Placebo Oral Tablet
Placebo single dose

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eidos Therapeutics	Celerion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetic Assessments: T1/2	Plasma half-life (t1/2)	30 days
Secondary	Pharmacokinetic Assessments: Tmax	Time to maximum concentration (Tmax)	30 days
Secondary	Pharmacokinetic Assessments: Cmax	Maximum concentration (Cmax)	30 days
Secondary	Pharmacokinetic Assessments: Cmin	Cmin	30 days
Secondary	Pharmacokinetic Assessments: AUC	Area under the plasma concentration-time curve (AUC)	30 days
Secondary	Pharmacokinetic Assessments: Clearance	Apparent clearance (CL/F)	30 days
Secondary	Pharmacokinetic Assessments: volume of distribution	Apparent volume of distribution (Vss/F)	30 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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