Evaluation of the Efficacy of Stiripentol (Diacomit) as Monotherapy for the Treatment of Primary Hyperoxaluria

Evaluation of the efficacy of stiripentol (Diacomit) as monotherapy for the treatment of primary hyperoxaluria.

Pilot clinical study, open, prospective and multicenter.

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria
• Intervention / Treatment: Drug: stiripentol (Diacomit)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Hopital Robert Debre
  • Paris, France
    • Hopital Necker
  • Paris, France
    • Hôpital Tenon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with primary hyperoxaluria type 1, 2 or 3, diagnosed according to standard methods
• Having at least one molar ratio [oxaluria / creatinuria] greater than 0.08 since diagnosis
• Having Glomerular Filtration Rate ≥ 45 mL / min / 1.73m2
• Age ≥ 6 months
• Having read, or whose parents have read, the information note and signed the consent form. For children, if their level of understanding allows, their assent will also be sought
• Proficient enough, or whose parents or legal representatives have sufficient mastery, the French language to read, understand and complete study documents
• Affiliate or beneficiary of a social security scheme
• Ability to respect the protocol, including treatment, and can be followed regularly in the study
• For pubertal patients, contraception deemed effective by the investigator or abstinence

Exclusion Criteria:

• Introduction, discontinuation or dose modification of vitamin B6 or potassium citrate treatment within 4 weeks prior to the inclusion visit
• Consumption of jelly candies and / or dark chocolate in the week preceding the study
• Patient having a kidney and / or liver transplant
• Presence of a clinically significant acute or chronic pathology, other than primary hyperoxaluria, that may interfere with the evaluation of the study results according to the investigator
• During biological or physical examinations, presence of significant anomaly (s) inconsistent with participation in the study according to the investigator
• History of severe allergy, asthma, skin rash or hypersensitivity to a drug
• Treatment affecting hepatic metabolism (cimetidine, ketoconazole, fluconazole, itraconazole, phenytoin, rifampicin, rifabutin) in progress or taken during the month preceding the start of the study
• Treatment affecting the renal tubule (probenecid, β-lactams, ...) in progress or taken during the last two weeks preceding the start of the study
• Presence of a pathology or treatment that, according to the investigator, renders the subject unfit
• Contraindications to stiripentol as defined in the current SmPC (hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC, history of psychosis in the form of delusional episodes)
• Pregnant or lactating woman
• Patient under guardianship
• Patient concurrently participating in another clinical trial or exclusion period following a previous trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: stiripentol (Diacomit)	Drug: stiripentol (Diacomit); Administration of stiripentol per os

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative variation (%) of the molar ratio [oxaluria / creatinuria] between baseline and after two weeks of treatment.	Relative variation (%) of the molar ratio [oxaluria / creatinuria] between baseline and after two weeks of treatment.	Change (%) of the molar ratio [oxaluria / creatinuria] between the baseline value (average of 3 measures done during pre-treatment period) and the value (average of 2 measures) after 2 weeks of treatment.
Relative variation (%) of the molar ratio [oxaluria / creatinuria] between baseline and after three weeks of treatment.	Relative variation (%) of the molar ratio [oxaluria / creatinuria] between baseline and after three weeks of treatment.	Change (%) of the molar ratio [oxaluria / creatinuria] between the baseline value (average of 3 measures done during pre-treatment period) and the value (average of 2 measures) after 3 weeks of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment defined by a decrease> 20% of the molar ratio [oxaluria / creatinuria]	Response to treatment defined by a decrease> 20% of the molar ratio [oxaluria / creatinuria]	3 measures from inclusion to first treatment intake (= baseline value), then 2 measures at Day 14 and Day 15 respectively (=value after 2 weeks of treatment), and 2 measures at Day 20 and Day 21 respectively (=value after 3 weeks of treatment)
Relative variation (%) of supersaturation of urine with calcium oxalate between the start and the end of treatment period	Relative variation (%) of supersaturation of urine with calcium oxalate between the start and the end of treatment period	3 measures from inclusion to first treatment intake (= baseline value), then 2 measures at Day 14 and Day 15 respectively (=value after 2 weeks of treatment), and 2 measures at Day 20 and Day 21 respectively (=value after 3 weeks of treatment)
Relative variation (%) in overall crystalline volume measured by crystalluria on fresh urine between the start and the end of treatment period	Relative variation (%) in overall crystalline volume measured by crystalluria on fresh urine between the start and the end of treatment period	3 measures from inclusion to first treatment intake (= baseline value), then 2 measures at Day 14 and Day 15 respectively (=value after 2 weeks of treatment), and 2 measures at Day 20 and Day 21 respectively (=value after 3 weeks of treatment)
Effect of stiripentol dose increase on absolute decrease of the molar ratio [oxaluria / creatinuria]	Effect of stiripentol dose increase on absolute decrease of the molar ratio [oxaluria / creatinuria]	3 measures from inclusion to first treatment intake (= baseline value), then 2 measures at Day 14 and Day 15 respectively (=value after 2 weeks of treatment), and 2 measures at Day 20 and Day 21 respectively (=value after 3 weeks of treatment)
Effect of stiripentol dose increase on relative decrease (%) of the molar ratio [oxaluria / creatinuria]	Effect of stiripentol dose increase on relative decrease (%) of the molar ratio [oxaluria / creatinuria]	3 measures from inclusion to first treatment intake (= baseline value), then 2 measures at Day 14 and Day 15 respectively (=value after 2 weeks of treatment), and 2 measures at Day 20 and Day 21 respectively (=value after 3 weeks of treatment)
Blood test results (hepatic assessment) at the start and at the end of the study	Blood test results (hepatic assessment) at the start and at the end of the study	From start of participation of the patient to end of the treatment period (up to 8 weeks)
Blood test results (blood cells count) at the start and at the end of the study	Blood test results (blood cells count) at the start and at the end of the study	From start of participation of the patient to end of the treatment period (up to 8 weeks)
Frequency and nature of the adverse events throughout the study	Frequency and nature of the adverse events throughout the study	From start of participation of the patient to end of the treatment period (up to 8 weeks)

Collaborators and Investigators

• Sponsor: Biocodex

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2019
• Primary Completion (Actual): December 18, 2020
• Study Completion (Actual): March 8, 2021

Study Registration Dates

• First Submitted: January 18, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary; Anticonvulsants; Stiripentol
• Other Study ID Numbers: HYPOP (STP194)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No