Autism Spectrum DisorderPhase 1NCT03912350
The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan
A Phase 1 study testing Balovaptan in people with Autism Spectrum Disorder, run by Hoffmann-La Roche.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Balovaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 26 Jun 2022to 13 Oct 2022
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
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- Exclusion Criteria for Participants with Hepatic Impairment:
- History within 3 months prior to Screening, or current symptoms of, hepatic encephalopathy Grade 2 and above.
- Evidence of severe ascites.
- Recent history of, or the treatment of, esophageal bleeding within 3 months of first dose, unless banded.
- Participants who have had a porto-systemic shunt.
- Participants who have a history of paracentesis within 3 months prior to Day -1.
- Participants who have a history of unstable diabetes mellitus as evidenced by hemoglobin A1c ≥ 9% at Screening.
- History of alcoholism within 3 months prior to Screening.
- Use of any prescription drugs within 30 days (or within 5 times the elimination half-life, if known, of the medication, whichever is longer) of first dose, with the exception of therapies for hepatic-associated disorders that have been stable for at least 60 days prior to first dose.
- Biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
- Positive result on human immunodeficiency virus (HIV) 1, HIV2, Hepatitis B Surface Antigen (HBsAg).
- History of presence of liver disease, injury, or dysfunction as indicated by any clinically significant deviations from normal reference ranges in liver function tests, unless approved by the Investigator of designee.
- Participants likely to need prescription medication during the study. Participants who have received any prescribed systemic or topical medication within 30 days (or within 5 times the elimination half-life, if known, of the medication, whichever is longer) of the first dose administration, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety.
- Any slow-release medicinal formulations considered to still be active within 4 weeks (or within 5 times the elimination half-life of the medication, whichever is longer) prior to the first study drug administration are prohibited, unless in the opinion of the Investigator or designee the medication will not interfere with the study procedures or compromise safety.
- History of alcoholism within 2 years prior to Screening.
- Positive result on HIV 1, HIV2, HBsAg, Hepatitis B core antibody (HBcAb), and/or HCV antibody.
- Signs and symptoms potentially indicative of peripheral neuropathy.
About this study
Official title: The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan: A Phase I, Multiple-Center, Open-Label Study Following Multiple Daily Oral Doses of Balovaptan in Subjects With Moderate Hepatic Impairment and Healthy Subjects With Normal Hepatic Function
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%).
- Conditions
- Autism Spectrum Disorder
- Being tested
- Balovaptan
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BalovaptanDrug
Participants will receive 1 tablet of balovaptan once daily (QD) on Days 1 through 14.
| Study group | Role | What they receive |
|---|---|---|
| Test group | Experimental | Participants with moderate hepatic impairment. Receives: Drug: Balovaptan |
| Reference group | Active comparator | Healthy pariticipants with normal hepatic function. Receives: Drug: Balovaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of balovaptan
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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 M3 metabolite, when possible
Measured: 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 outcomes (1)
Percentage of participants with adverse events
Measured: Up to approximately 18 weeks from screening (screening is up to 28 days prior to admission to the clinical research unit).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start26 Jun 2022 (estimated)
- Primary completion24 Sep 2022 (estimated)
- Study completion13 Oct 2022 (estimated)
Why it stopped: The study is on hold due to stopping of the Autism Spectrum Disorder program with balovatpan, the study drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03912350
- Sponsor's protocol ID
- WP41045
- Status last verified
- Feb 2022
- First submitted
- 10 Apr 2019
- Last updated
- 8 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).