EpilepsyPhase 1NCT03681158

Study of Excretion Balance and Pharmacokinetics of [14C]-Sodium Valproate (3.7 MBq) in Healthy Postmenopausal or Permanently Sterile Female Subjects

A Phase 1 study testing sodium valproate in people with Epilepsy, run by Sanofi at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Primary Objectives: To determine the excretion balance and systemic exposure of radioactivity after oral administration of [14C]-sodium valproate (VPA) . To determine the pharmacokinetics of sodium VPA and metabolite(s) and its contribution to the overall exposure of radioactivity. Read more about this study

Who is it for?: Ages 30 to 60 years, women onlyHealthy volunteers can take part
Conditions the study is for: Epilepsy
What is being tested?: sodium valproate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited Kingdom
Study dates: 5 Oct 2018to 11 Apr 2019
Phase: Phase 1
Are there results?: None posted in the registry

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 30 to 60 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Female subjects, between 30 and 60 years of age, inclusive.
Body weight between 40.0 and 90.0 kg, inclusive, body mass index between 18.0 and 30.0 kg/m2, inclusive.
Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
Normal vital signs after 10 minutes resting in supine position: 95 mmHg < systolic blood pressure (SBP) <140 mmHg or, for subjects over 45 years of age, <150 mmHg, 45 mmHg < diastolic blood pressure (DBP) <90 mmHg, 40 bpm < heart rate (HR) <100 bpm
Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges; 120 ms<PR<220 ms, QRS<120 ms, QTc≤450 ms and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant, or for subjects over 45 years of age, standard 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator, with QTc≤470 ms.
Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however, serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase), and total bilirubin (unless the subject has documented Gilbert syndrome) should not exceed the upper laboratory norm.

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Surgically and permanently sterile (hysterectomy, bilateral salpingectomy or bilateral salpingo-oophorectomy) at least 3 months earlier or postmenopausal. Menopause is defined as being amenorrheic for at least 2 years with plasma FSH level > 30 UI/L. No additional contraception is required.
Having given written informed consent prior to undertaking any study-related procedure.
Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
Not under any administrative or legal supervision.
Normal renal function as expressed by a creatinine clearance > 80 mL/min as calculated by the Cockroft and Gault formula

Who cannot join

Any subject with specific dietary habits, such as vegan.
Any subject with irregular bowel habits (more than 3 bowel movements/day or less than 1 every 2 days).
Any subject undergoing dental care or presenting with dental caries.
Any subject who is occupationally exposed to radiation as defined in the Ionising Radiations Regulations 2017.
Participation in a trial with 14C-radiolabelled medication in the 12 months preceding the study.
Radiation exposure, including that from the present study and radiopharmaceuticals or radionuclides in therapeutic or diagnostic procedures, but excluding background radiation, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years.

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Poor metabolizer status for CYP2C9, CYP2C19, CYP2D6 (by genotyping).
Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days before inclusion.
Any contra-indications to sodium VPA according to the applicable labeling (including personal or family history of severe hepatic dysfunction, urea cycle disorders, porphyria, hypersensitivity to valproate, active liver disease, pregnancy, child bearing potential) and patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding mitochondrial enzyme polymerase γ (POLG, e.g. Alpers-Huttenlocher Syndrome).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Investigational site number
Nottingham

Other trials in United Kingdom

About this study

Official title: An Open-label Study of Excretion Balance and Pharmacokinetics Following a Single Oral Dose of [14C]-Sodium Valproate (3.7 MBq) in Healthy Postmenopausal or Permanently Sterile Female Subjects

Primary Objectives:

To determine the excretion balance and systemic exposure of radioactivity after oral administration of [14C]-sodium valproate (VPA) .
To determine the pharmacokinetics of sodium VPA and metabolite(s) and its contribution to the overall exposure of radioactivity.
To collect samples in order to determine the metabolic pathways of sodium VPA and identify the chemical structures and main excretion route of the main metabolites.

Secondary Objective:

To assess the clinical and biological tolerability of oral solution of sodium VPA.

Read the detailed description

Total study duration is 3 to 10 weeks, including a screening period of 8 to 28 days, treatment period of up to 15 days and a follow-up and end of study of up to 4 weeks.

Conditions: Epilepsy
Being tested: sodium valproate
Medical subject headings: Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

sodium valproateDrug
Also called LA40220
Pharmaceutical form:Powder for oral solution reconstituted with water Route of administration: Oral

Study groups in NCT03681158
Study group	Role	What they receive
sodium valproate	Experimental	Single oral dose of sodium valproate containing [14C]-sodium VPA Receives: Drug: sodium valproate

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of radioactive dose excreted in urine and feces
Fractional and cumulative percentage of radioactive dose excreted in urine and feces
Measured: Day 1 to Day 43
Assessment of key metabolite(s) of sodium valproate
key metabolite(s) of sodium valproate will be assessed in plasma, urine and feces.
Measured: Day 1 to Day 43
Assessment of PK parameters: Cmax
Maximum plasma or blood concentration observed
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: tmax
Time to reach Cmax (tmax)
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: AUClast
Area under the plasma concentration versus time curve calculated from time zero to the real time, tlast (time corresponding to the last concentration above the limit of quantification, Clast (AUClast)
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: AUC
Area under the plasma concentration versus time curve extrapolated to infinity (AUC)
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: t1/2z
Terminal half-life associated with the terminal slope (λz) (t1/2z) in plasma, blood radioactivity and plasma VPA
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: B/P (blood/plasma radioactivity ratio)
Blood to plasma radioactivity ratio calculated at each time point
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: RCmax (VPA to radioactivity ratio for plasma Cmax)
RCmax is calculated as Cmax(VPA)/Cmax (radioactivity)
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Assessment of PK parameters: RAUC (VPA to radioactivity ratio for plasma AUC)
RAUC is calculated as AUC(VPA)/AUC (radioactivity)
Measured: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43

Secondary outcomes (1)

Safety- Adverse Events
Adverse events, spontaneously reported by the subject or observed by the Investigator from day -1 to day 43
Measured: From day -1 to 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Oct 201811 Apr 2019

First posted21 Sep 2018
Study start5 Oct 2018
Primary completion11 Apr 2019
Study completion11 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for EpilepsyStudies of the same condition, open and under way.
More trials run by SanofiThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03681158
Sponsor's protocol ID: BEX15316
Other IDs: 2017-004987-36, U1111-1205-1651, 2017
Status last verified: Apr 2022
First submitted: 14 Sep 2018
Last updated: 25 Apr 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Study of Excretion Balance and Pharmacokinetics Following a Single Oral Dose of [14C]-Sodium Valproate (3.7 MBq) in Healthy Postmenopausal or Permanently Sterile Female Subjects
ClinicalTrials.gov ID: NCT03681158
Acronym / sponsor ID: BEX15316
Conditions: Epilepsy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Study start: 5 Oct 2018 (actual)
Primary completion: 11 Apr 2019 (actual)
Study completion: 11 Apr 2019 (actual)
First posted: 21 Sep 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objectives:

To determine the excretion balance and systemic exposure of radioactivity after oral administration of [14C]-sodium valproate (VPA) .
To determine the pharmacokinetics of sodium VPA and metabolite(s) and its contribution to the overall exposure of radioactivity.
To collect samples in order to determine the metabolic pathways of sodium VPA and identify the chemical structures and main excretion route of the main metabolites.

Secondary Objective:

To assess the clinical and biological tolerability of oral solution of sodium VPA.

Detailed description

Total study duration is 3 to 10 weeks, including a screening period of 8 to 28 days, treatment period of up to 15 days and a follow-up and end of study of up to 4 weeks.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
sodium valproate	Experimental	Drug: sodium valproateSingle oral dose of sodium valproate containing [14C]-sodium VPA

Who may qualify

Ages: 30 to 60 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Female subjects, between 30 and 60 years of age, inclusive.
Body weight between 40.0 and 90.0 kg, inclusive, body mass index between 18.0 and 30.0 kg/m2, inclusive.
Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
Normal vital signs after 10 minutes resting in supine position: 95 mmHg < systolic blood pressure (SBP) <140 mmHg or, for subjects over 45 years of age, <150 mmHg, 45 mmHg < diastolic blood pressure (DBP) <90 mmHg, 40 bpm < heart rate (HR) <100 bpm
Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges; 120 ms<PR<220 ms, QRS<120 ms, QTc≤450 ms and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant, or for subjects over 45 years of age, standard 12-lead ECG without clinically significant abnormality, in the judgment of the Investigator, with QTc≤470 ms.

Key exclusion criteria (10 listed)

Any subject with specific dietary habits, such as vegan.
Any subject with irregular bowel habits (more than 3 bowel movements/day or less than 1 every 2 days).
Any subject undergoing dental care or presenting with dental caries.
Any subject who is occupationally exposed to radiation as defined in the Ionising Radiations Regulations 2017.
Participation in a trial with 14C-radiolabelled medication in the 12 months preceding the study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
sodium valproateAlso: LA40220Pharmaceutical form:Powder for oral solution reconstituted with water Route of administration: Oral	Drug	sodium valproate

Primary outcome

Percentage of radioactive dose excreted in urine and feces
Time frame: Day 1 to Day 43
Fractional and cumulative percentage of radioactive dose excreted in urine and feces
Assessment of key metabolite(s) of sodium valproate
Time frame: Day 1 to Day 43
key metabolite(s) of sodium valproate will be assessed in plasma, urine and feces.
Assessment of PK parameters: Cmax
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Maximum plasma or blood concentration observed
Assessment of PK parameters: tmax
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Time to reach Cmax (tmax)
Assessment of PK parameters: AUClast
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Area under the plasma concentration versus time curve calculated from time zero to the real time, tlast (time corresponding to the last concentration above the limit of quantification, Clast (AUClast)
Assessment of PK parameters: AUC
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Area under the plasma concentration versus time curve extrapolated to infinity (AUC)
Assessment of PK parameters: t1/2z
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Terminal half-life associated with the terminal slope (λz) (t1/2z) in plasma, blood radioactivity and plasma VPA
Assessment of PK parameters: B/P (blood/plasma radioactivity ratio)
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
Blood to plasma radioactivity ratio calculated at each time point
Assessment of PK parameters: RCmax (VPA to radioactivity ratio for plasma Cmax)
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
RCmax is calculated as Cmax(VPA)/Cmax (radioactivity)
Assessment of PK parameters: RAUC (VPA to radioactivity ratio for plasma AUC)
Time frame: Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43
RAUC is calculated as AUC(VPA)/AUC (radioactivity)

1 secondary outcome

Safety- Adverse Events
Time frame: From day -1 to 43

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Related trials for Epilepsy

Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Sciences & Operations study director

Sanofi

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sodium valproate in people with Epilepsy, run by Sanofi at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of radioactive dose excreted in urine and feces (time frame: Day 1 to Day 43). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03681158.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.