A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children With Autism Spectrum Disorder
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Intervention: Balovaptan
Intervention description: Participants were to receive an oral dose of balovaptan once a day (QD) for a 6-week treatment period, followed by an optional extension period of 48 weeks.
Intervention MeSH terms: Balovaptan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 2 Years
Maximum age: 4 Years
Healthy volunteers: No

Summary:

      This was a Phase Ib, multicenter, open-label study in children 2-4 years old with autism
      spectrum disorder (ASD) to investigate the pharmacokinetics, safety, and tolerability of an
      oral dose of balovaptan once a day (QD). The study was to consists of a 6-week treatment
      period to evaluate the pharmacokinetics of balovaptan in 2 to 4 year old children followed by
      an optional extension period of 48 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of ASD according to Diagnostic and Statistical Manual of Mental Disorders,
             Fifth Edition (DSM-5) criteria for ASD. Diagnostics will be performed by a team of
             autism experts and confirmed by Autism Diagnostic Observation ScheduleTM, Second
             Edition (ADOS-2) criteria. The DSM-5 criteria for diagnosis of autism must be met with
             the highest confidence in the opinion of the investigator. Children with ambiguous
             diagnostic results cannot be enrolled in the study. If the ADOS-2 assessment has been
             performed by a certified rater and documented within 12 months of the screening visit,
             it is not mandatory to repeat it unless the subject was assessed below an age of 2
             years.

          -  Hearing and vision compatible with the study assessments, as judged by the
             investigator

          -  Ability for subject and the caregiver to comply with the study protocol, in the
             investigator's judgment

          -  Availability of a parent or other reliable caregiver who is fluent in language of the
             site and has frequent and sufficient contact with the subject.

        Exclusion Criteria:

          -  Clinically significant psychiatric and/or neurologic comorbidity that may interfere
             with the safety or efficacy endpoints in the view of the investigator

          -  Clinically significant regression of any acquired language and motor function skills
             in the opinion of the investigator throughout the subject's development

          -  History of seizures with the exception of a single, non-complicated febrile seizure >=
             6 months before screening

          -  Clinical diagnosis of peripheral neuropathy or signs and symptoms indicative of
             peripheral neuropathy

          -  Any clinically relevant cardiovascular disease

          -  Confirmed elevation in cardiac troponin I (cTn I), high-sensitive cardiac troponin T
             (hs cTn T), N-terminal pro-B-type natriuretic peptide (NT-proBNP) or, if conducted,
             clinically relevant abnormality in Doppler echocardiogram

          -  Confirmed clinically significant abnormality on ECG at screening, including, but not
             limited to, a QT interval corrected through use of Fridericia's formula (QTcF) of >=
             450 ms, absence of dominating sinus rhythm, or second- or third-degree
             atrioventricular block

          -  Confirmed systolic or diastolic blood pressure above the 95th percentile or below the
             5th percentile according to the Centers for Disease Control and Prevention (CDC) norm
             tables referring to stature (height)-for-age percentiles

          -  Confirmed heart rate: >150 bpm in 2-year old children, >135 bpm in 3-year old
             children, or >120 bpm in 4-year old children.

          -  Concomitant disease or condition that could interfere with, or treatment of which
             might interfere with, the conduct of the study; or discontinuation of prohibited
             medication that might pose unacceptable risks to the subject in the opinion of the
             investigator

          -  Evidence for current GI disease that would interfere with the conduct of the study or
             pose unacceptable risks in the opinion of the investigator

          -  History of coagulopathies, bleeding disorders, or blood dyscrasias

          -  Positive serology for HIV-1 or HIV-2

          -  Confirmed clinically significant abnormality in parameters of hematology, clinical
             chemistry, coagulation, or urinalysis, specifically a confirmed absolute neutrophil
             count (ANC) <LLN Children with confirmed CPK elevations exceeding 2 x upper limit of
             normal (ULN) will be excluded

          -  History of malignancy

          -  Clinically significant loss of blood within 3 months prior to screening

          -  Unstable use of permitted medications for 4 weeks before screening

          -  Use of prohibited medications within 30 days (or 5 times the half-life, whichever is
             longer) prior to initiation of study treatment