ClinicalTrials.gov record NCT07241234
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 1b study evaluates AG-181 tablets in people with phenylketonuria (PKU). It aims to assess safety, tolerability, and how the drug is absorbed and processed in the body, while measuring blood phenylalanine. Treatment is given in defined cohorts (up to 28 days) in an open-label, non-randomized design.
What it is studying. The study is testing the safety and tolerability of AG-181 in people with PKU and measuring how the drug behaves in the body (pharmacokinetics) and how it affects phenylalanine levels (pharmacodynamics). It collects data on drug concentrations over time and on any side effects.
What the researchers hope to learn. Collect safety and tolerability data, measure pharmacokinetic parameters (Cmax, Tmax, AUC, clearance, volume), and assess changes in phenylalanine concentrations to inform further clinical development of AG-181.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- AG-181
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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 informed consent.
- 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.
- Body mass index (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 CYP3A 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.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After screening (including genetic testing and blood tests for phenylalanine), participants will receive oral AG-181 tablets (Cohort 1: dosing from Day 1 to Day 28; an optional cohort also receives AG-181 per the protocol). They will have repeated blood samples for drug levels, pharmacokinetics, and phenylalanine measurements during dosing and safety assessments, with adverse-event monitoring through Day 42. Participants may need to stop certain medications before the first dose and must follow a consistent protein/Phe diet approved by a dietitian. Procedures described in the registry are mainly genetic testing, blood draws, dietitian review, and safety exams.
How the study is structured. Interventional, open-label (no placebo), non-randomized study with sequential cohorts. Participants receive AG-181 tablets (one cohort receives drug from Day 1 to Day 28; an optional second cohort may also receive AG-181) with safety follow-up and blood sampling for drug levels and phenylalanine.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in Poland, United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on phenylketonuria
Important dates
- Study start
- Apr 17, 2026
- Primary completion
- Jan 17, 2028 (estimated)
- Study completion
- Jan 17, 2028 (estimated)
- Target enrollment
- 20 participants (estimated)
- Last updated on registry
- Sep 28, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Agios Pharmaceuticals, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Agios Medical Affairs 📞 833-228-8474 ✉ medinfo@agios.com
Participating sites (5)
- Indiana UniversityRecruiting
Indianapolis, Indiana, 46202 · United States
- UPMC Children's Hospital of PittsburghRecruiting
Pittsburgh, Pennsylvania, 15224 · United States
- University of Texas Southwestern Medical Center (UTSW)Recruiting
Dallas, Texas, 75390 · United States
- Uniwersyteckie Centrum Kliniczne (Medical University of Gdansk)Recruiting
Gdansk, Pomeranian Voivodeship, 80-952 · Poland
- Centrum Wsparcia Badań Klinicznych Pomorskiego Uniwersytetu Medycznego w SzczecinieRecruiting
Szczecin, West Pomeranian Voivodeship, 71-252 · Poland
Terms used on this page · explanations by MedicalUpdates.ai
- primary purpose
- The main reason an interventional study is being done, for example treatment, prevention, diagnosis, supportive care or basic science.
- during Screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- timeframe
- The period over which an outcome is measured, for example 'at 12 weeks'. It is not necessarily the total length of the study.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- washout
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- Key Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Key Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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