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CompletedNCT03294707Updated Sep 19, 2024

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

A Phase 1 interventional study of AG10 oral tablet and Placebo Oral Tablet in Amyloid Cardiomyopathy, Transthyretin-Related, sponsored by Eidos Therapeutics, a BridgeBio company. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by Eidos Therapeutics, a BridgeBio company · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
56
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Amyloid Cardiomyopathy, Transthyretin-Related

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03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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;
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
56 participants (actual)

Study arms

  • Experimental
    AG10 single oral dose

    AG10 oral tablet, administered by mouth, once

    Drug: AG10 oral tablet

  • Placebo comparator
    Placebo single oral dose

    Placebo Oral Tablet, administered by mouth, once

    Drug: Placebo Oral Tablet

Interventions

  • DrugAG10 oral tablet

    Active single ascending dose

    Also known as: Eidos Therapeutics AG10

  • DrugPlacebo Oral Tablet

    Placebo single dose

    Also known as: Matching placebo

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 30 days

Secondary outcomes

  1. Pharmacokinetic Assessments: T1/2

    Plasma half-life (t1/2)

    Time frame: 30 days

  2. Pharmacokinetic Assessments: Tmax

    Time to maximum concentration (Tmax)

    Time frame: 30 days

  3. Pharmacokinetic Assessments: Cmax

    Maximum concentration (Cmax)

    Time frame: 30 days

  4. Pharmacokinetic Assessments: Cmin

    Cmin

    Time frame: 30 days

  5. Pharmacokinetic Assessments: AUC

    Area under the plasma concentration-time curve (AUC)

    Time frame: 30 days

  6. Pharmacokinetic Assessments: Clearance

    Apparent clearance (CL/F)

    Time frame: 30 days

  7. Pharmacokinetic Assessments: volume of distribution

    Apparent volume of distribution (Vss/F)

    Time frame: 30 days

  8. 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).

    Time frame: 30 days

  9. Pharmacodynamic Assessments: Western blot

    AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: Immunoblotting (Western Blot)

    Time frame: 30 days

  10. Pharmacodynamic Assessments: prealbumin

    AG10 binding to and/or stabilization of TTR will be evaluated by established ex vivo assays: quantitation of prealbumin (TTR).

    Time frame: 30 days

  11. 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.

    Time frame: 30 days

  12. 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.

    Time frame: 30 days

06

Study locations

1 site
  • Celerion
    Tempe, Arizona 85283, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03294707
Lead sponsor
Eidos Therapeutics, a BridgeBio company
Collaborators
Celerion
Responsible party
Sponsor
First posted
Sep 27, 2017
Start date
Sep 11, 2017
Primary completion
Feb 5, 2018
Completion
May 18, 2018
Last update
Sep 19, 2024

Study contacts

Terry O'Reilly, M.D.
principal investigator · Celerion

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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