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

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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04049578

Enrollment

Registered

2019-08-08

Start date

2019-12-19

Completion date

2020-05-06

Last updated

2020-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autism Spectrum Disorder

Brief 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.

Interventions

DRUGBalovaptan

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 4 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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
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 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
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

Secondary

Measure	Time frame
Number of Participants With Adverse Events	Up to approximately week 20

Countries

United States

Participant flow

Participants by arm

Arm	Count
Balovaptan 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.	2
Total	2

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Physician Decision	1

Baseline characteristics

Characteristic	Balovaptan
Age, Continuous	3.45 Years STANDARD_DEVIATION 0.78
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 2
other Total, other adverse events	2 / 2
serious Total, serious adverse events	0 / 2

Outcome results

Primary

Area Under the Curve at Steady State (AUCss) of Balovaptan

Time frame: 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