Pharmacokinetics and Tolerability of Sulthiame

NCT03400189 | Completed Phase 1 DMC

• 1 other identifier: C01CS
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This preliminary pilot exploration aims at specifying the pharmacokinetic parameters of sulthiame, formulated as an immediate release tablet, thus helping to design proper clinical trials for the future assessment of new paediatric formulations currently under development. The clinical tolerability to single doses of sulthiame will also be closely monitored to orient future trials.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (4)

• Elimination half-life of sultiame after single doses of 50, 100 and 200 mg of sulthiame in 4 healthy volunteers.

  Sultiame plasma concentration will be measured at predefined times after dose administration, the results will be plotted graphically and traditional pharmacokinetic calculations (log-linear regression) will be used to derive estimates of this pharmacokinetic parameter. This is a descriptive outcome and no statistical test is applied.

  9 weeks

• Area Under curve (AUC) of sultiame after single doses of 50, 100 and 200 mg of sulthiame in 4 healthy volunteers.

  Sultiame plasma concentration will be measured at predefined times after dose administration, the results will be plotted graphically and traditional pharmacokinetic calculations (numerical integration through trapezoidal rule) will be used to derive estimates of this pharmacokinetic parameter. This is a descriptive outcome and no statistical test is applied.

  9 weeks

• Systemic drug clearance of sultiame after single doses of 50, 100 and 200 mg of sulthiame in 4 healthy volunteers.

  Sultiame concentration will be measured at predefined times after dose administration, the results will be plotted graphically and traditional pharmacokinetic calculations (ratio of administered dose over AUC) will be used to derive estimates of this pharmacokinetic parameter. This is a descriptive outcome and no statistical test is applied.

  9 weeks

• Distribution volume of sultiame after single doses of 50, 100 and 200 mg of sulthiame in 4 healthy volunteers.

  Sultiame plasma concentration will be measured at predefined times after dose administration, the results will be plotted graphically and traditional pharmacokinetic calculations (product of clearance by half-life divided by the logarithm of 2) will be used to derive estimates of this pharmacokinetic parameter. This is a descriptive outcome and no statistical test is applied.

  9 weeks

Secondary Outcomes (4)

• Dose linearity of plasma exposure to sultiame

  9 weeks

• Plasma free fraction of sultiame

  9 weeks

• Erythrocyte binding of sultiame

  9 weeks

• Validation of a liquid chromatography-mass spectrometry (LC-MS/MS) assay method for the determination of sultiame in biological fluids

  9 weeks

Study Arms (1)

Single arm

OTHER

Single oral dose of sulthiame (Ospolot® tablets) * Period I: 50 mg * Period II: 100 mg * Period III: 200 mg given 3 weeks apart

Drug: Sulthiame

Interventions

Sulthiame DRUG

Single dose (50, 100, 200 mg)

Also known as: Ospolot

Single arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects aged between 18 and 45 years.
• Body weight (BW) ranging between 55 and 95 kg, providing body mass index (BMI) is between 18 and 29 kg/m2
• Absence of significant findings in the medical history and physical examination as judged by the Investigator, especially for cardiovascular, pulmonary, haematological and nervous systems
• Absence of significant laboratory abnormalities as judged by the Investigator. Gilbert's syndrome (increased total and unconjugated bilirubin when fasting) will be accepted if mild
• Absence of clinically significant abnormalities on 12-lead electrocardiogram (ECG)
• Negative urine drug screen (amphetamines, benzodiazepines, cannabis, cocaine, opiates)
• Commitment to refrain from travels outside Europe over the whole study duration.
• Ability to understand the procedures, agreement to participate and willingness to give written informed consent
• Co-operative attitude and availability for scheduled visits over the entire study period.

You may not qualify if:

• History of major cardiovascular, pulmonary, hepatic, immunological, renal, haematological, gastrointestinal, genitourinary, neurological, or rheumatologic disorders
• Active diseases of any type, including inflammatory disorders and infections. Mild acne is permissible providing no systemic or local treatment is provided or planned (except for cleaning lotions)
• History of significant allergy or asthma. Allergic rhinitis or conjunctivitis is acceptable if non symptomatic when starting the study and if symptoms are not anticipated to occur during the study to a point that would require corticosteroid therapy (e.g. in case of annual use)
• History of cardiovascular dysfunction if considered as clinically relevant (conduction abnormality, arrhythmia, bradycardia, angina pectoris, cardiac hypertrophy unless elicited by training, pulmonary embolism)
• Hypertension defined as supine blood pressure \>150/90 mmHg or recurrent hypotensive events considered as clinically relevant or documented orthostatic hypotension
• Sick sinus syndrome, known long QT syndrome, reproducible observation of QTc \>440 msec or of pronounced sinus bradycardia (\<40 bpm/min)
• Intense sport activities. Moderate sport is acceptable and activities should remain fairly constant throughout the study
• Any clinically significant laboratory value on screening that are not within normal range on single repeat (Gilbert's syndrome acceptable if mild)
• Positive hepatitis B \& C antigen screen
• Positive HIV antibody screen or screen not performed
• Any recent acute illness or sequelae thereof which could expose the subject to a higher risk or might confound the results of the study
• Treatment in the previous three months with any drug known to have well-defined potential for toxicity to a major organ
• History of hypersensitivity to any drug if considered as serious including sulthiame or the excipients of the study formulation
• Use of any medication the week prior to study or as based on 5 plasma half-life rule and throughout study, including aspirin or other over-the-counter (OTC) preparation. Paracetamol is permissible before and during study as a concomitant medication but only with Investigator's permission.
• Participation in a clinical investigation or blood donation of 500 ml within the past 3 months

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• Advicenne Pharma: collaborator

Study Sites (1)

Division of Clinical Pharmacology

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Epilepsy

Interventions

sulthiame

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Phase I, single centre, prospective, ascending single oral doses, open-label, 3-period clinical trial

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: January 17, 2018
• Study Start: February 12, 2018
• Primary Completion: May 22, 2018
• Study Completion: August 30, 2018
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

CH (1)