Pharmacokinetic Parameters of Stiripentol in Renal Impaired Patients and Matching Controls With Normal Renal Function

NCT05735951 | Completed Phase 1 DMC

• 1 other identifier: JADE
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether the pharmacokinetics (PK) of stiripentol and of its relevant metabolites would be altered in subjects with renal impairment compared with normal controls in order to assess the need of dose adjustment in the renal impaired population. This study will include subjects with mild, moderate and severe renal impairment.

Conditions

Chronic Renal Insufficiency

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration versus time curve

  Area under the plasma concentration versus time curve: AUC0-12 (corresponding to AUC0-tau), in order to assess the need of dose adjustment in the renal impaired population.

  Steady state at Day15

• Peak Plasma Concentration

  Peak Plasma Concentration: Cmax in order to assess the need of dose adjustment in the renal impaired population.

  Steady state at Day15

Secondary Outcomes (25)

• Peak Plasma Concentration, for stiripentol in plasma

  Day 1 and Day 15 when applicable

• The area under the concentration-time curve from time zero (pre-dose) to 12 h post-dose, for stiripentol in plasma

  Day 1 and Day 15 when applicable

• The time at which Cmax is apparent, for stiripentol in plasma

  Day 1 and Day 15 when applicable

• The area under the concentration-time curve from time zero (pre-dose) to 24 h post-dose, for stiripentol in plasma

  Day 1 and Day 15 when applicable

• The area under the concentration-time from time zero (pre-dose) to the time of last quantifiable concentration, for stiripentol in plasma

  Day 1 and Day 15 when applicable

Study Arms (4)

Mild renally impaired patients

EXPERIMENTAL

Mild renally impaired patients

Drug: STIRIPENTOL oral administration

Moderate renally impaired patients

EXPERIMENTAL

Moderate renally impaired patients

Drug: STIRIPENTOL oral administration

Severe renally impaired patients

EXPERIMENTAL

Severe renally impaired patients

Drug: STIRIPENTOL oral administration

Matching controls

EXPERIMENTAL

Matching volunteer without renal impairement

Drug: STIRIPENTOL oral administration

Interventions

STIRIPENTOL oral administration DRUG

Oral administration of: * Days 1 and 2: 1000 mg of stiripentol (single dose at the end of breakfast), * Day 3 to Day 14: 1000 mg of stiripentol bis in die (BID) (approximately 12 hours apart, at the end of breakfast and at the end of dinner), * Day 15: 1000 mg of stiripentol (single dose at the end of breakfast).

Also known as: Multiple oral administration of stiripentol 1000 mg bis in die (BID)

Matching controls; Mild renally impaired patients; Moderate renally impaired patients; Severe renally impaired patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, aged 18 to 80 years inclusive,
• Females participating in this study must be of non-childbearing potential or using highly effective contraception for the full duration of the study and for 1 month after the end of treatment,
• Negative serum pregnancy test at screening and urinary pregnancy test at Day -1 (if applicable),
• A negative antigen test for Coronavirus Disease 19 (COVID 19),
• Normal hepatic function (AST \< 3xULN (Upper limit normal), ALT (Alanine aminotransferase); \<1.5 ULN; bilirubin),
• Non-smoker subject or smoker of not more than 5 cigarettes a day,
• Signing a written informed consent in their native language prior to selection,
• Documented renal impairment indicated by reduced RF at least 12 months of screening or longer,
• Stable renal function (eGFR) as evidenced by ≤ 30% difference in two evaluations of Renal function (RF) on two separate occasions separated by at least 28 days with one measurement being the value at screening,
• Renal impairment within the following ranges (using the Modification of Diet in Renal Disease-4 (MDRD4) equation) at screening:
• mild renal impairment with eGFR ≥ 60 to \< 90 mL/min/1.73 m²,
• moderate renal impairment with eGFR ≥ 30 to \< 60 mL/min/1.73 m²,
• severe renal impairment with eGFR \< 30 mL/min/1.73 m² and not on dialysis,
• Supine blood pressure (BP) ≤ 180/104 mmHg,
• Heart rate between 50-100 bpm, DBP between 40-100 mmHg and SBP between 90-170 mmHg extremities excluded,

You may not qualify if:

• Unsuitable veins for repeated venipuncture,
• Positive Hepatitis B surface (HBsAg) antigen or positive Hepatitis C Virus (HCV), or positive results for Human Immunodeficiency Virus (HIV)-1 or 2 tests,
• History or presence of drug or alcohol abuse (alcohol consumption \>40 grams/day),
• Subject/Patient who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development,
• Subject/Patient who cannot be contacted in case of emergency,
• History or presence of allergy or unusual reactions to some drugs or anesthetics or known hypersensitivity to the investigation product or its excipients (including lactose intolerance), test material or related compound,
• Who receive a medication known to affect both cyochromes (CYP) CYP1A2, CYP3A4, and CYP2C19, such as rifampin, within 1 month prior to the first dose administration. Concomitant use of medications known to strongly affect either CYP1A2, CYP3A4, or CYP2C19, such as phenytoin, phenobarbital or carbamazepine, should be avoided within 1 month prior to the first dose administration.
• Administrative or legal supervision,
• Blood donation (including in the frame of a clinical trial) within 2 months before administration,
• Subject/Patient who is pregnant, in labour or breastfeeding. Subject/Patient should not be enrolled if she plans to become pregnant during the time of study participation,
• Excessive consumption of beverages with xanthine bases (\> 4 cups or glasses / day),
• Positive COVID 19 antigen test, or COVID-19 vaccination within 14 days of the first dosing.
• The consumption of grapefruit/grapefruits production, Sevilla oranges, or any poppy seeds, are not allowed from 7 days prior to the first study drug administration,
• Evidence or history of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic, systemic, infectious, or allergic disease (including drug hypersensitivity or allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). However, investigator will have the possibility to judge whether a subject could be included with uncontrolled disease (e.g. in case of non-treated dyslipidemia),
• General anesthesia within 3 months before administration,

Sponsors & Collaborators

• Biocodex: lead

Study Sites (1)

Mc Comac Medical

Sofia, 1612, Bulgaria

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Diyan Genov, MD

  Comac Medical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 21, 2023
• Study Start: July 24, 2023
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)