A Study to Assess the Potential for Pre-systemic Inhibition of CYP3A by Idebenone Using Midazolam as a Substrate

An Open-label Study to Assess the Potential for Pre-systemic Inhibition of Cytochrome P450 3A4 (CYP3A) by Idebenone in Healthy Male Subjects Using Midazolam as a Substrate

This phase I open label study is conducted to assess the potential pharmacokinetic interaction of Raxone® with midazolam in healthy male volunteers

Study Overview

• Status: Completed
• Conditions: Drug-Drug Interaction
• Intervention / Treatment: Drug: Raxone (idebenone 150 mg); Drug: Midazolam 2,5 mg

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Gières, France, 38610
    • Eurofins Optimed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male aged 18 to 55 years.
2. A Body Mass Index (BMI) of 18-30. BMI = Body weight (kg) / Height (m)2.
3. Male subject willing to use an acceptable effective contraceptive measure for the entire duration of study participation.
4. No clinically significant abnormal serum biochemistry, haematology and urine examination values.
5. A negative urinary test for drugs of abuse and alcohol breath screen. A positive alcohol test may be repeated at the discretion of the Investigator.
6. Negative HIV and Hepatitis B and C results.
7. No clinically significant abnormalities in 12 lead electrocardiogram (ECG).
8. No clinically significant abnormalities in blood pressure, pulse or oral temperature.
9. No allergy or sensitivity to midazolam, idebenone or any of their excipients.
10. No current or past medical condition that might significantly affect the pharmacokinetic or pharmacodynamic response to midazolam.
11. Subject must be available to complete the study (including follow-up visit).
12. Subject must satisfy a medical examiner about their fitness to participate in the study.
13. Subject must provide written informed consent to participate in the study.
14. Covered by Health Insurance System and/or in compliance with the recommendations of National Law in force relating to biomedical research.

Exclusion Criteria:

1. A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
2. Use of any medication (prescription or OTC, including health supplements and herbal remedies, except paracetamol, within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of trial medication.
3. Use of any medication known to induce or inhibit any of the enzymes within the CYP3A system within 28 days of Day 1, or grapefruit within 7 days of Day 1
4. Evidence of renal, hepatic dysfunction, cardiovascular or metabolic dysfunction.
5. History of obstructive sleep apnoea syndrome.
6. History of any significant drug allergy including benzodiazepine.
7. A clinically significant history of drug or alcohol abuse.
8. Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
9. Participation in a clinical trial of a New Chemical Entity within the previous 3 months or of a Marketed Product within the previous 30 days (or 5 times the half-life, whichever is longer).
10. Donation of 450 mL or more blood within the previous 3 months.
11. Smoking or use of tobacco products or substitutes within the previous 6 months, as determined at the Screening visit.
12. Need for administrative or legal supervision.
13. Subject who would receive more than 4500 euros as indemnities for participation in biomedical research within 12 months, including the indemnities for the present study.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve (AUC) from the time of dosing to the time of the last observed concentration (AUC0-t)	13 days
Area Under the Curve (AUC) extrapolated to infinity from dosing time, based on the last observed concentration (AUC0-∞)	13 days
Maximum plasma concentration (Cmax)	13 days
Time to Maximum plasma concentration (Cmax) during a dosing interval (tmax)	13 days
Terminal elimination half-life (t1/2)	13 days
Clearance, calculated as dose/AUC0-∞ (CL/F)	13 days
Volume of distribution during terminal phase after non-intravenous administration (Vz/F)	13 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve (AUC) from the time of dosing to the time of the last observed concentration (AUC0-t)	13 days
Area Under the Curve (AUC) extrapolated to infinity from dosing time, based on the last observed concentration (AUC0-∞)	13 days
Maximum plasma concentration (Cmax)	13 days
Time to Maximum plasma concentration (Cmax) during a dosing interval (tmax)	13 days
Terminal elimination half-life (t1/2)	13 days
Clearance, calculated as dose/AUC0-∞ (CL/F)	13 days
Volume of distribution during terminal phase after non-intravenous administration (Vz/F)	13 days
Clearance (CL)	13 days
Volume of distribution (Vz)	13 days

Collaborators and Investigators

• Sponsor: Santhera Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 29, 2016
• First Posted (Estimate): September 2, 2016

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Protective Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antioxidants; Midazolam; Idebenone
• Other Study ID Numbers: SNT-I-017