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

Drug-Drug Interaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02887443
• Other study ID #: SNT-I-017
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2016
• Last updated: October 4, 2017
• Start date: September 2016
• Est. completion date: November 2016

Study information

• Verified date: October 2017
• Source: Santhera Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug-Drug Interaction

Intervention

Drug:
• Raxone (idebenone 150 mg)
Raxone (idebenone 300 mg t.i.d.) on days 3 and days 5 to 10
• Midazolam 2,5 mg
Midazolam (2,5 mg single oral dose) on days 1, 3 and 10

Locations

Country	Name	City	State
France	Eurofins Optimed	Gières

Sponsors (1)

Lead Sponsor	Collaborator
Santhera Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve (AUC) from the time of dosing to the time of the last observed concentration (AUC0-t)		13 days
Primary	Area Under the Curve (AUC) extrapolated to infinity from dosing time, based on the last observed concentration (AUC0-8)		13 days
Primary	Maximum plasma concentration (Cmax)		13 days
Primary	Time to Maximum plasma concentration (Cmax) during a dosing interval (tmax)		13 days
Primary	Terminal elimination half-life (t1/2)		13 days
Primary	Clearance, calculated as dose/AUC0-8 (CL/F)		13 days
Primary	Volume of distribution during terminal phase after non-intravenous administration (Vz/F)		13 days
Secondary	Area Under the Curve (AUC) from the time of dosing to the time of the last observed concentration (AUC0-t)		13 days
Secondary	Area Under the Curve (AUC) extrapolated to infinity from dosing time, based on the last observed concentration (AUC0-8)		13 days
Secondary	Maximum plasma concentration (Cmax)		13 days
Secondary	Time to Maximum plasma concentration (Cmax) during a dosing interval (tmax)		13 days
Secondary	Terminal elimination half-life (t1/2)		13 days
Secondary	Clearance (CL)		13 days
Secondary	Clearance, calculated as dose/AUC0-8 (CL/F)		13 days
Secondary	Volume of distribution (Vz)		13 days
Secondary	Volume of distribution during terminal phase after non-intravenous administration (Vz/F)		13 days