search
Back to results

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

Primary Purpose

Amyloid Cardiomyopathy, Transthyretin-Related

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AG10 oral tablet
Placebo Oral Tablet
Sponsored by
Eidos Therapeutics, a BridgeBio company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloid Cardiomyopathy, Transthyretin-Related

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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;

Sites / Locations

  • Celerion

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AG10 single oral dose

Placebo single oral dose

Arm Description

AG10 oral tablet, administered by mouth, once

Placebo Oral Tablet, administered by mouth, once

Outcomes

Primary Outcome 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.
To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects

Secondary Outcome Measures

Pharmacokinetic Assessments: T1/2
Plasma half-life (t1/2)
Pharmacokinetic Assessments: Tmax
Time to maximum concentration (Tmax)
Pharmacokinetic Assessments: Cmax
Maximum concentration (Cmax)
Pharmacokinetic Assessments: Cmin
Cmin
Pharmacokinetic Assessments: AUC
Area under the plasma concentration-time curve (AUC)
Pharmacokinetic Assessments: Clearance
Apparent clearance (CL/F)
Pharmacokinetic Assessments: volume of distribution
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.
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
AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)
Pharmacodynamic Assessments: prealbumin
AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).
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.
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.

Full Information

First Posted
September 18, 2017
Last Updated
May 21, 2018
Sponsor
Eidos Therapeutics, a BridgeBio company
Collaborators
Celerion
search

1. Study Identification

Unique Protocol Identification Number
NCT03294707
Brief Title
Single and Multiple Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of AG10
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
September 11, 2017 (Actual)
Primary Completion Date
February 5, 2018 (Actual)
Study Completion Date
May 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eidos Therapeutics, a BridgeBio company
Collaborators
Celerion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloid Cardiomyopathy, Transthyretin-Related

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Subjects will be randomized with an overall ratio of 3:1 to AG10: placebo within each cohort
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AG10 single oral dose
Arm Type
Experimental
Arm Description
AG10 oral tablet, administered by mouth, once
Arm Title
Placebo single oral dose
Arm Type
Placebo Comparator
Arm Description
Placebo Oral Tablet, administered by mouth, once
Intervention Type
Drug
Intervention Name(s)
AG10 oral tablet
Other Intervention Name(s)
Eidos Therapeutics AG10
Intervention Description
Active single ascending dose
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Matching placebo
Intervention Description
Placebo single dose
Primary Outcome Measure Information:
Title
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.
Description
To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Pharmacokinetic Assessments: T1/2
Description
Plasma half-life (t1/2)
Time Frame
30 days
Title
Pharmacokinetic Assessments: Tmax
Description
Time to maximum concentration (Tmax)
Time Frame
30 days
Title
Pharmacokinetic Assessments: Cmax
Description
Maximum concentration (Cmax)
Time Frame
30 days
Title
Pharmacokinetic Assessments: Cmin
Description
Cmin
Time Frame
30 days
Title
Pharmacokinetic Assessments: AUC
Description
Area under the plasma concentration-time curve (AUC)
Time Frame
30 days
Title
Pharmacokinetic Assessments: Clearance
Description
Apparent clearance (CL/F)
Time Frame
30 days
Title
Pharmacokinetic Assessments: volume of distribution
Description
Apparent volume of distribution (Vss/F)
Time Frame
30 days
Title
Pharmacodynamic Assessments: Assessments of TTR stabilization will be listed and summarized by part, treatment, and time point using appropriate descriptive statistics.
Description
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).
Time Frame
30 days
Title
Pharmacodynamic Assessments: Western blot
Description
AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)
Time Frame
30 days
Title
Pharmacodynamic Assessments: prealbumin
Description
AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).
Time Frame
30 days
Title
Food effect: AUC
Description
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.
Time Frame
30 days
Title
Food effect: Cmax
Description
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.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terry O'Reilly, M.D.
Organizational Affiliation
Celerion
Official's Role
Principal Investigator
Facility Information:
Facility Name
Celerion
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85283
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs