A Phase 1, Randomized, Open-Label, Crossover Study to Evaluate the Relative Oral Bioavailability of 2 Formulations of PTC923 and the Food Effect on the Phase 3 Formulation When Administered as a Single Dose to Healthy Subjects

INTERVENTION: This is a Phase 1, open‐label, randomized, single dose, crossover study consisting of 2 independent parts: a relative bioavailability study of 2 formulations (Formulation A and Formulation B) and 2 doses of PTC923 (Part A); and a food effect study of Formulation B (Part B) in in healthy adult subjects. Subjects are permitted to participate in one study part (Part A or Part B) only. Part A is a cross over study between Formulation A and Formulation B. Part A and Part B are independent of each other. Part B is a cross over study between fasted and fed of Formulation B. Mode of administration: Oral suspension. Formulation B is a powder mixed with water and Formulation A is a powder mixed with ‘Medisca Oral Mix’ oral suspension. Ingestion will be under clinical monitoring. Subjects are inpatients at CMAX. Laboratory tests for PK will also confirm ingestion. Part A Subjects will be randomized into the 2 treatment sequences of PTC923 in a 1:1 ratio. Each treatment is a single dose, and each treatment will be separated from the next by a minimum of 3‐day washout period. Sequence 1: 20 mg/kg Formulation A PTC923, 20 mg/kg Formulation B PTC923, 60 mg/kg Formulation A PTC923, and 60 mg/kg Formulation B PTC923 ‐all administered concurrent with a low‐fat meal. Sequence 2: 20 mg/kg Formulation B PTC923, 20 mg/kg Formulation A PTC923, 60 mg/kg Formulation B PTC923, and 60 mg/kg Formulation A PTC923 ‐all administered concurrent with a low‐fat meal. Part B Subjects will be randomized into the 2 treatment sequences of PTC923 in a 1:1 ratio. Each treatment is a single dose, and each treatment will be separated from the next by a minimum of 3‐day washout period. Subjects will only receive Formulation B PTC923 in this study part. Sequence CONDITION: Phenylketonuria (PKU); ; Phenylketonuria (PKU) Metabolic and Endocrine ‐ Metabolic disorders PRIMARY OUTCOME: Part A, Primary Outcome ‐ This is a composite outcome. ; ; To assess the relative bioavailability of the analytes BH4 and sepiapterin following administration of 2 dose levels (20 and 60 mg/kg/day) and 2 formulations (Formulation B: the Phase 3 formulation powder in water, and Formulation A: the Phase 1/2 formulation powder in Medisca Oral Mix) of PTC923 under fed conditions (low‐fat diet) in healthy adult subjects[For each dose, blood samples will be collected for PK analysis of sepiapterin and BH4 from subjects at: ; Day 1, Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 4, Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 7 Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 10 Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; ; ] Part B, Primary Outcome ; ; To assess the effect of food on 2 dose levels of PTC923 Formulation B in healthy adult subjects.; [For each dose, blood samples will be collected for PK analysis of sepiapterin and BH4 from subjects at: ; Day 1, Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 4, Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 7 Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; Day 10 Predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose.; ; ] SECONDARY OUTCOME: To assess the safety and tolerability of a single oral administration of PTC923 under fed conditions in healthy adult subjects. ; This is assessed by the following: ; [Day 7 (24‐48 hours after Day 5). The timepoint noted as Day 7 is really Day 6 or 7, as this timepoint is between 24‐48 hours after Day 5 timepoint. ; See timepoints for assessment here: ; 12‐Lead ECG at Screening, Day‐1, D1, D3, D4, D6, D7, D9, D10. ECGs performed in triplicate at Screening, D1, D4, D7, D10 ; Physician exam at Screening, Day‐1, D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11. ; 12‐Lead ECG , Physician exam, Vital Signs, Height, PK blood sample, Adverse events monitoring, Safety follow up, and Clinical laboratory tests including clinical chemistry panel, hematology panel, and urinalysis. ; Vital Signs at Screening, Day‐1, D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11. Height assessed with vital signs only at the Screening visit. ; PK blood sample at Day 1, D2, D4, D5, D7, D8, D10, D11 ; Adverse events monitoring at Screening, Day‐1, D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11, EOS 48 hours after discharge, Safety follow up 30 days after last dose ; Clinical laboratory tests include clinical chemistry panel, hematology panel, and urinalysis. Clinical labs will be taken at Screening, Day‐1, D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11 ; ] To assess the palatability of Formulation B using a visual analogue scale to rate formulation parameters of odor, taste, and aftertaste. This is a composite potability scale. [Day 7 (24‐48 hours after Day 5). The timepoint noted as Day 7 is really Day 6 or 7, as this timepoint is between 24‐48 hours after Day 5 timepoint.] INCLUSION CRITERIA: Individuals eligible to participate in this study include those who meet all of the following INCLUSION CRITERIA: 1. Males or females aged between 18 and 55 years old and have a Body Mass Index between 18.5 and 30.0 kg/m squared 2. Subjects must understand the nature of the study and must provide signed and dated written informed consent before the conduct of any study‐related procedures. 3. Women of childbearing potential must have a negative pregnancy testing at Screening and agree to abstinence or the use of effective forms of contraception (with a failure rate of less than 1% per year when used consistently and correctly. Highly effective contraception or abstinence must be continued for the duration of the study and for up to 30 days after the last dose of study drug. 4. Males with female partners of childbearing potential must agree to use barrier contraceptive and their female partners must use a highly effective method of contraception f