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

Phase 1

Completed

• Conditions: Epilepsy
• Interventions: Drug: sodium valproate

• Registration Number: NCT03681158
• Lead Sponsor: Sanofi

Brief 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.

* 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 Timeline

• Study First Submitted: 2018-09-14
• Study First Submitted QC: 2018-09-20
• Study First Posted: 2018-09-21
• Study Start: 2018-10-05
• Primary Completion: 2019-04-11
• Study Completion: 2019-04-11
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-21
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sodium valproate	sodium valproate	Single oral dose of sodium valproate containing \[14C\]-sodium VPA

Primary Outcome Measures

Name	Time	Method
Assessment of PK parameters: Cmax	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	Day 1 to 8, Day 12 to Day 15, Day 22, Day 29, Day 36, Day 43	Time to reach Cmax (tmax)
Assessment of key metabolite(s) of sodium valproate	Day 1 to Day 43	key metabolite(s) of sodium valproate will be assessed in plasma, urine and feces.
Assessment of PK parameters: t1/2z	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
Percentage of radioactive dose excreted in urine and feces	Day 1 to Day 43	Fractional and cumulative percentage of radioactive dose excreted in urine and feces
Assessment of PK parameters: AUClast	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: B/P (blood/plasma radioactivity ratio)	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: AUC	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: RAUC (VPA to radioactivity ratio for plasma AUC)	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)
Assessment of PK parameters: RCmax (VPA to radioactivity ratio for plasma Cmax)	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)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Investigational site number; 🇬🇧 Nottingham, United Kingdom