A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children With Autism Spectrum Disorder

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib, Multicenter, Open-Label, 6-Week Study With a 48-Week Extension to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children Ages 2-4 Years With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Balovaptan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balovaptan<br> | Drug: Balovaptan<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve at Steady State (AUCss) of Balovaptan |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 
| Plasma Concentration of Balovaptan |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 
| Plasma Concentration of M2 Metabolite, as Applicable |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 
| Plasma Concentation of M3 Metabolite |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 
| Plasma Concentration Ratio of M2 to Balovaptan, as Applicable |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 
| Plasma Concentration Ratio of M3 to Balovaptan |  | Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | Up to approximately week 20 |