ClinicalTrials.gg
RecruitingNCT07241234Updated Oct 28, 2026

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria

A Phase 1 interventional study of AG-181 in Phenylketonuria, sponsored by Agios Pharmaceuticals, Inc.. Recruiting at 5 sites in 2 countries. Open to participants aged 18 Years to 69 Years. Per ClinicalTrials.gov, last updated 2026-10-28.

Sponsored by Agios Pharmaceuticals, Inc. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Started Apr 2026; still recruiting 6 months later.
Updated Sep 28, 20261 site addedGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
18 Years to 69 Years
Sex
All
01

Study summary

The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).

02

Conditions studied

  • Phenylketonuria

Browse trials for

03

In context

Phenylketonurias

191 studies on the registry are indexed under Phenylketonurias; 40 are open to participants now.

This study's planned enrollment of 20 is below the median of 27 across 122 interventional studies indexed under Phenylketonurias.

Browse Phenylketonurias studies →

Lead sponsor

Agios Pharmaceuticals, Inc. is the lead sponsor of 52 studies on the registry; 6 are open to participants now.

Of its 23 completed or terminated interventional studies of FDA-regulated products, 4 (17%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 69 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Diagnosis of PKU, defined as documented presence of 2 mutant alleles in the phenylalanine hydroxylase (PAH) gene, of which at least 1 is the R408W mutation, as determined during Screening per the genotyping performed by the study central genotyping laboratory.
  • At least 1 plasma Phe concentration greater than (>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing .
  • Average concentration of plasma Phe > 600 μmol/L in Phe samples taken during Screening, with no individual assessment below 360 μmol/L. Any Phe samples taken after Day -20 will not be included.
  • (BMI) greater than or equal to (≥) 18.0 kilograms per meter square (kg/m\^2) to lesser than or equal to (≤) 35.0 kg/m\^2 and weight ≥ 50 kilograms (kg) at any time during the Screening Period.
  • Documented approval from a dietitian confirming that the subject can maintain their diet consistent in protein and Phe intake throughout the study as outlined in the Diet Manual.

Key Exclusion Criteria:

  • Prior exposure to AG-181.
  • Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥ 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug.
  • Receiving products that are strong inhibitors or strong inducers of cytochrome P450 CYP1A2, CYP2C8, or that have not been stopped for ≥ 28 days before administration of the first dose of study drug.
  • Receiving treatment with an acid-reducing agent, including but not limited to proton pump inhibitors and H2 blockers. Short-acting acid-reducing agents such as calcium carbonate are permitted.
  • Any preexisting condition that could (in the opinion of the Investigator) interfere with gastrointestinal anatomy or motility that may disrupt the absorption, metabolism, and/or excretion of the study drug.
  • Any preexisting condition that could (in the opinion of the Investigator) interfere with hepatic or renal function that may disrupt the absorption, metabolism, and/or excretion of the study drug.
  • Inability to tolerate oral medication.
  • Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening.
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
20 participants (estimated)

Study arms

  • Experimental
    Cohort 1: AG-181

    Subjects will receive AG-181 from Day 1 to Day 28.

    Drug: AG-181

  • Experimental
    Cohort 2 (Optional Cohort): AG-181

    Subjects will receive AG-181.

    Drug: AG-181

Interventions

  • DrugAG-181

    AG-181 film-coated tablets

06

What researchers measure

Primary outcomes

  1. Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug

    Time frame: Up to Day 42

Secondary outcomes

  1. Plasma Concentration of AG-181

    Time frame: Up to Day 28

  2. Maximum Concentration (Cmax) of AG-181

    Time frame: Up to Day 28

  3. Time to Maximum (Peak) Concentration (Tmax) of AG-181

    Time frame: Up to Day 28

  4. Area Under the Concentration-Time Curve (AUC) of AG-181

    Time frame: Up to Day 28

  5. Apparent Total Body Clearance (CL/F) of AG-181

    Time frame: Up to Day 28

  6. Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181

    Time frame: Up to Day 28

  7. Change From Baseline in Phenylalanine (Phe) Concentration

    Time frame: Baseline up to Day 28

07

Study locations

5 of 5 sites recruiting
  • Indiana University
    Indianapolis, Indiana 46202, United States
    Recruiting
  • UPMC Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15224, United States
    Recruiting
  • University of Texas Southwestern Medical Center (UTSW)
    Dallas, Texas 75390, United States
    Recruiting
  • Uniwersyteckie Centrum Kliniczne (Medical University of Gdansk)
    Gdansk, Pomeranian Voivodeship 80-952, Poland
    Recruiting
  • Centrum Wsparcia Badań Klinicznych Pomorskiego Uniwersytetu Medycznego w Szczecinie
    Szczecin, West Pomeranian Voivodeship 71-252, Poland
    Recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

2 registry updates since Sep 25, 2026
Sites
1 site added
Show site
  • Uniwersyteckie Centrum Kliniczne (Medical University of Gdansk) · Gdansk, Poland
Sep 28, 2026
Show all 2 updates
  1. Oct 28, 2026
    Minor edits only
    + 1 other change: verification date
  2. Sep 28, 2026
    1 site added
    Show site
    • Uniwersyteckie Centrum Kliniczne (Medical University of Gdansk) · Gdansk, Poland
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07241234
Responsible party
Sponsor
First posted
Nov 21, 2025
Start date
Apr 17, 2026
Primary completion
Jan 17, 2028 (estimated)
Completion
Jan 17, 2028 (estimated)
Last update
Oct 28, 2026

Study contacts

Agios Medical Affairs
Contact
medinfo@agios.com
833-228-8474

Oversight

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

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