Autism Spectrum Disorder
Conditions
Brief summary
This is a multi-center, non-randomized, open-label, parallel group, multiple-dose study to assess the pharmacokinetic, safety, and tolerability of balovaptan in male and female subjects with moderate hepatic impairment compared to healthy subjects with normal hepatic function matched by age (±10 years), sex, and body mass index (BMI; ±20%).
Interventions
DRUGBalovaptan
Participants will receive 1 tablet of balovaptan once daily (QD) on Days 1 through 14.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for All Participants: * BMI between 18 and 40 kg/m2, inclusive. * Women of childbearing potential must either: agree to use one highly effective contraceptive method combined with a barrier method from Screening until 90 days after the last dose of study drug or practice true abstinence because of the subject's lifestyle choice; be in an exclusively same-sex relationship. * For men: agreement to use contraceptive measures * Females of child-bearing potential must refrain from donating ova from Day -1 until 90 days after the safety Follow-up visit. Males must refrain from donating sperm from Day -1 until 90 days after the safety Follow-up visit. Inclusion Criteria for Participants with Hepatic Impairment: * Stable, documented moderate liver disease diagnosed \>6 months and stable for at least 3 months prior to Screening. * Participants with moderate hepatic impairment may have medical findings consistent with their hepatic dysfunction. Participants with abnormal findings considered in line with underlying hepatic disease by the Investigator will be eligible. Inclusion Criteria for Healthy Participants: * Healthy status is defined by no clinically significant findings from medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, chemistry, and urinalysis at Screening and/or Day -1 as assessed by the Investigator (or designee). Gilbert's syndrome is acceptable.
Exclusion criteria
for All Participants: * History of significant hypersensitivity, intolerance, or allergy to any drug compound, constituents or excipients of the study drug, food, or other substance, unless approved by the Investigator (or designee). * History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs. * Evidence of hepatorenal syndrome and estimated creatinine clearance range \<60 mL/min or abnormal and clinically significant sodium and potassium levels, as determined by the Investigator (or designee). * Female subjects of childbearing potential with a positive serum pregnancy test at Screening and/or at admission (Day -1), or who are lactating. * History of drug/chemical abuse within 2 years prior to Screening; current active substance abuse will not be permitted. * Known personal or family history of congenital long QT syndrome or sudden unexplained death.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of M3 metabolite, when possible | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Plasma concentration of balovaptan | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Plasma concentration of M2 metabolite, as applicable | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Plasma concentration of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| AUC during the dosing interval on Day 1 of balovaptan | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 |
| AUC during the dosing interval on Day 1 of M2 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 |
| AUC during the dosing interval on Day 1 of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 |
| AUC during the dosing interval at steady state on Day 14 of balovaptan | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| AUC during the dosing interval at steady state on Day 14 of M2 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| AUC during the dosing interval at steady state on Day 14 of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Maximum observed plasma concentration (Cmax) of balovaptan | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Maximum observed plasma concentration (Cmax) of M2 metabolite | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Maximum observed plasma concentration (Cmax) of M3 metabolite | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Time of maximum observed plasma concentration (Tmax) of balovaptan | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Time of maximum observed plasma concentration (Tmax) of M2 metabolite | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Time of maximum observed plasma concentration (Tmax) of M3 metabolite | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Metabolite:Parent ratio of area under the plasma (MRauc) of M2 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Metabolite:Parent ratio of area under the plasma (MRauc) of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Metabolite:Parent ratio of maximum observed plasma (MRcmax) of M2 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Metabolite:Parent ratio of maximum observed plasma (MRcmax) of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent volume of distribution (V/F) of balovaptan | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent volume of distribution (V/F) of M2 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent volume of distribution (V/F) of M3 metabolite | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Terminal phase rate constant (λZ) of balovaptan, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Terminal phase rate constant (λZ) of M2 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Terminal phase rate constant (λZ) of M3 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent terminal elimination half-life (t½) of balovaptan, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent terminal elimination half-life (t½) of M2 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent terminal elimination half-life (t½) of M3 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent plasma clearance after oral administration (CLss/F) of balovaptan, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent plasma clearance after oral administration (CLss/F) of M2 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent plasma clearance after oral administration (CLss/F) of M3 metabolite, when possible | Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of balovaptan, when possible | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
| Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of M2 metabolite, when possible | 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants with adverse events | Up to approximately 18 weeks from screening (screening is up to 28 days prior to admission to the clinical research unit). |
Outcome results
None listed