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

Overview

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

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 5, 2018

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

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

Arms, Groups and Cohorts

  • Experimental: AG10 single oral dose
    • AG10 oral tablet, administered by mouth, once
  • Placebo Comparator: Placebo single oral dose
    • Placebo Oral Tablet, administered by mouth, once

Clinical Trial Outcome Measures

Primary Measures

  • 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.
    • Time Frame: 30 days
    • To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects

Secondary Measures

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

Participating in This Clinical Trial

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;

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Eidos Therapeutics, a BridgeBio company
  • Collaborator
    • Celerion
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Terry O’Reilly, M.D., Principal Investigator, Celerion

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