---
title: A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
nct_id: NCT07241234
overall_status: RECRUITING
phase: PHASE1
sponsor: Agios Pharmaceuticals, Inc.
study_type: INTERVENTIONAL
primary_condition: Phenylketonuria
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT07241234.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT07241234"
ct_last_update_post_date: 2026-04-24
last_seen_at: "2026-05-12T06:35:36.985Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria

**Official Title:** A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria

**NCT ID:** [NCT07241234](https://clinicaltrials.gov/study/NCT07241234)

## Key Facts

- **Status:** RECRUITING
- **Phase:** PHASE1
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 20
- **Lead Sponsor:** Agios Pharmaceuticals, Inc.
- **Conditions:** Phenylketonuria
- **Start Date:** 2026-04-21
- **Completion Date:** 2028-01-17
- **CT.gov Last Update:** 2026-04-24

## Brief Summary

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

## Eligibility

- **Minimum age:** 18 Years
- **Maximum age:** 69 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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 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.
```

## Arms

- **Cohort 1: AG-181** (EXPERIMENTAL) — Subjects will receive AG-181 from Day 1 to Day 28.
- **Cohort 2 (Optional Cohort): AG-181** (EXPERIMENTAL) — Subjects will receive AG-181.

## Interventions

- **AG-181** (DRUG) — AG-181 film-coated tablets

## Primary Outcomes

- **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

- **Plasma Concentration of AG-181** _(time frame: Up to Day 28)_
- **Maximum Concentration (Cmax) of AG-181** _(time frame: Up to Day 28)_
- **Time to Maximum (Peak) Concentration (Tmax) of AG-181** _(time frame: Up to Day 28)_
- **Area Under the Concentration-Time Curve (AUC) of AG-181** _(time frame: Up to Day 28)_
- **Apparent Total Body Clearance (CL/F) of AG-181** _(time frame: Up to Day 28)_
- **Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181** _(time frame: Up to Day 28)_
- **Change From Baseline in Phenylalanine (Phe) Concentration** _(time frame: Baseline up to Day 28)_

## Locations (1)

- University of Texas Southwestern Medical Center (UTSW), Dallas, Texas, United States — _RECRUITING_

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.university of texas southwestern medical center (utsw)|dallas|texas|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT07241234.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT07241234*  
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