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

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ClinicalTrials.gov Identifier: NCT03294707
Recruitment Status : Completed
First Posted : September 27, 2017
Last Update Posted : May 23, 2018
Sponsor:
Collaborator:
Celerion
Information provided by (Responsible Party):
Eidos Therapeutics

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

Condition or disease Intervention/treatment Phase
Amyloid Cardiomyopathy, Transthyretin-Related Drug: AG10 oral tablet Drug: Placebo Oral Tablet Phase 1

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  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Subjects will be randomized with an overall ratio of 3:1 to AG10: placebo within each cohort
Primary Purpose: Treatment
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
Actual Study Start Date : September 11, 2017
Actual Primary Completion Date : February 5, 2018
Actual Study Completion Date : May 18, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AG10 single oral dose
AG10 oral tablet, administered by mouth, once
Drug: AG10 oral tablet
Active single ascending dose
Other Name: Eidos Therapeutics AG10

Placebo Comparator: Placebo single oral dose
Placebo Oral Tablet, administered by mouth, once
Drug: Placebo Oral Tablet
Placebo single dose
Other Name: Matching placebo




Primary Outcome Measures :
  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. [ Time Frame: 30 days ]
    To evaluate the safety and tolerability of single and multiple doses of AG10 administered to healthy adult subjects


Secondary Outcome Measures :
  1. Pharmacokinetic Assessments: T1/2 [ Time Frame: 30 days ]
    Plasma half-life (t1/2)

  2. Pharmacokinetic Assessments: Tmax [ Time Frame: 30 days ]
    Time to maximum concentration (Tmax)

  3. Pharmacokinetic Assessments: Cmax [ Time Frame: 30 days ]
    Maximum concentration (Cmax)

  4. Pharmacokinetic Assessments: Cmin [ Time Frame: 30 days ]
    Cmin

  5. Pharmacokinetic Assessments: AUC [ Time Frame: 30 days ]
    Area under the plasma concentration-time curve (AUC)

  6. Pharmacokinetic Assessments: Clearance [ Time Frame: 30 days ]
    Apparent clearance (CL/F)

  7. Pharmacokinetic Assessments: volume of distribution [ Time Frame: 30 days ]
    Apparent volume of distribution (Vss/F)

  8. 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).

  9. 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)

  10. 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).

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03294707


Locations
United States, Arizona
Celerion
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Eidos Therapeutics
Celerion
Investigators
Principal Investigator: Terry O'Reilly, M.D. Celerion

Responsible Party: Eidos Therapeutics
ClinicalTrials.gov Identifier: NCT03294707     History of Changes
Other Study ID Numbers: AG10-001
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases