Otsuka's JNT-517 completes PKU Phase 1/2 study with enrollment reset to 163
The first-in-human trial of Otsuka's SLC6A19 inhibitor closed out after five completion-date changes and a swing from 111 back to 163 participants, with safety and PK data from the study still to post.
Executive Summary
- A first-in-human study of Otsuka's JNT-517 in phenylketonuria has moved to Completed status, with its final enrollment count settling higher than the figure last reported.
- This early-stage study's safety and pharmacokinetic findings feed directly into two later-stage trials of the same drug that are already recruiting, making its closeout the last checkpoint before those larger readouts.
- The record shows an active multi-part design that grew arms and revised its completion timeline repeatedly over three years, changes consistent with a seamlessly expanding first-in-human protocol rather than a program in distress.
- JNT-517 sits alone among industry programs targeting this specific transporter in phenylketonuria, while several other companies pursue the disease through different mechanisms, including enzyme substitution and gene therapy.
The closeout
NCT05781399, a six-part Phase 1/Phase 2 study of JNT-517 in healthy volunteers and people with phenylketonuria (PKU, a metabolic disorder that impairs the body's ability to break down the amino acid phenylalanine), is now recorded as Completed. The registry's most recent update lists enrollment at 163 and a primary completion date of July 29, 2025. That enrollment figure has moved several times over the past year: from 112 to 135 in June 2025, down to 111 when the trial was marked complete in May 2026, and back up to 163 in the July 16, 2026 update. NCT05781399+1First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaNCT05781399First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaJul 16, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the study tested
The trial's primary endpoint is the number of participants with treatment-emergent adverse events, tracked from screening through Day 8, 21, or 35 depending on the study part. Its six parts spanned single- and multiple-ascending-dose safety testing in healthy volunteers, a food-effect and formulation comparison, and two Phase 2 cohorts in PKU patients measuring changes in urinary amino acid levels, including phenylalanine, over four weeks. JNT-517 targets SLC6A19, a transporter also known as B0AT1, and is administered orally. No results have yet posted to ClinicalTrials.gov for this study. NCT05781399First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaNCT05781399
Reading the registry churn
The primary completion date changed five times since the trial's 2023 registration, moving from December 2023 to December 2024, June 2025, September 2025, and finally back to July 2025, a cumulative shift the sponsor's own multi-part, seamless-enrollment design (later parts opening while earlier parts were still running) helps explain. The trial's title and phase designation were also updated in June 2025 to add a Phase 2 component and two new study parts, consistent with the protocol's built-in flexibility rather than a redesign forced by a setback. Enrollment across the full multi-part study reached 163, above the earlier post-recruitment count of 135, indicating additional participants were captured in the final registry sweep rather than lost. NCT05781399First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaNCT05781399
What follows this trial
Otsuka already has two Phase 3 JNT-517 trials recruiting in PKU: NCT06971731, targeting a primary completion in March 2028, and NCT06628128, a long-term study enrolling 240 participants with a November 2027 completion target. A separate Phase 2 adolescent study, NCT06637514, has also completed. The first-in-human study's safety and pharmacokinetic findings, once posted, will sit underneath those larger, already-enrolling programs as the dose-selection basis for the ongoing registrational effort. NCT05781399First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaNCT05781399
Where JNT-517 sits in the field
Among industry-sponsored PKU programs, JNT-517 is the only SLC6A19-targeted small molecule in active testing; the nearest comparator is Otsuka's own Phase 3 trial of the same drug. Other PKU programs use distinct mechanisms: PTC Therapeutics' sepiapterin targets BH4 metabolism, BioMarin's pegvaliase and sapropterin work through enzyme substitution or cofactor pathways, and several gene-therapy programs from BioMarin, Sanofi, and NGGT target the PAH gene directly. This is a mechanistically diverse field where no single approach has established itself as dominant, and JNT-517's transporter-inhibition approach remains untested outside Otsuka's own trials. NCT05781399First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With PhenylketonuriaNCT05781399
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.