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

NCT02887443 | Completed Phase 1

• 1 other identifier: SNT-I-017
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Drug-Drug Interaction

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (9)

• 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

Interventions

Raxone (idebenone 150 mg) DRUG

Raxone (idebenone 300 mg t.i.d.) on days 3 and days 5 to 10

Midazolam 2,5 mg DRUG

Midazolam (2,5 mg single oral dose) on days 1, 3 and 10

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
• 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.
• 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
• Evidence of renal, hepatic dysfunction, cardiovascular or metabolic dysfunction.
• History of obstructive sleep apnoea syndrome.
• History of any significant drug allergy including benzodiazepine.
• A clinically significant history of drug or alcohol abuse.
• Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
• 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).
• Donation of 450 mL or more blood within the previous 3 months.
• Smoking or use of tobacco products or substitutes within the previous 6 months, as determined at the Screening visit.
• Need for administrative or legal supervision.
• 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.

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

Location

MeSH Terms

Interventions

idebenone

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2016
• First Posted: September 2, 2016
• Study Start: September 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: October 5, 2017

Record last verified: 2017-10

Locations

FR (1)