A Study of PTC923 in Participants With Phenylketonuria
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: PTC923; Placebo
Intervention description: PTC923 powder for oral use will be suspended in water or apple juice prior to administration.; Placebo matching to PTC923
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 157.0
Sex: All
Healthy volunteers: No

Summary:

      The main purpose of this trial is to evaluate the efficacy of PTC923 in reducing blood
      phenylalanine (Phe) levels in participants with phenylketonuria as measured by mean change in
      blood Phe levels from baseline to Weeks 5 and 6 (that is, the average of each respective
      treatment dose 2-week period of double-blind treatment).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Uncontrolled blood Phe level ≥360 μmol/L on current therapy anytime during screening
             and uncontrolled blood Phe level ≥360 μmol/L on current therapy when taking the
             average of the 3 most recent Phe levels from the participant's medical history
             (inclusive of the screening value).

          -  Clinical diagnosis of phenylketonuria with hyperphenylalaninemia (HPA) documented by
             past medical history of at least 2 blood Phe measurements ≥600 μmol/L.

          -  Women of childbearing potential must have a negative pregnancy test at screening and
             agree to abstinence or the use of at least one highly effective form of contraception
             for the duration of the study, and for up to 90 days after the last dose of study
             drug.

          -  Males who are sexually active with women of childbearing potential who have not had a
             vasectomy must agree to use a barrier method of birth control during the study and for
             up to 90 days after the last dose of study drug. Males must also refrain from sperm
             donations during this time period.

          -  Willing to continue current diet unchanged while participating in the study.

        Exclusion Criteria:

          -  Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel
             disease, chronic gastritis, and peptic ulcer disease, etc.) that could affect the
             absorption of study drug.

          -  History of gastric surgery, including Roux-en-Y gastric bypass surgery or an
             antrectomy with vagotomy, or gastrectomy.

          -  History of allergies or adverse reactions to synthetic tetrahydrobiopterin (BH4) or
             sepiapterin.

          -  Current participation in any other investigational drug study or use of any
             investigational agent within 30 days prior to screening.

          -  Any clinically significant laboratory abnormality as determined by the investigator.

          -  A female who is pregnant or breastfeeding, or considering pregnancy.

          -  Serious neuropsychiatric illness (for example, major depression) not currently under
             medical control, that in the opinion of the investigator or sponsor, would interfere
             with the participant's ability to participate in the study or increase the risk of
             participation for that participant.

          -  Past medical history and/or evidence of renal impairment and/or condition including
             moderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 milliliters
             [mL]/minute [min]) and/or under care of a nephrologist.

          -  Any abnormal physical examination and/or laboratory findings indicative of signs or
             symptoms of renal disease, including calculated GFR <60 mL/min/1.73 square meter
             (m^2).

          -  Requirement for concomitant treatment with any drug known to inhibit folate synthesis
             (for example, methotrexate).

          -  Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic
             mutations in 6-pyruvoyltetrahydropterin synthase, recessive guanosine-5'-triphosphate
             (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or
             pterin-4-alpha-carbinolamine dehydratase genes.

          -  Major surgery within the prior 90 days of screening.

          -  Concomitant treatment with BH4 supplementation (for example, sapropterin
             dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).

          -  Unwillingness to washout from BH4 supplementation (for example, sapropterin
             dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)