A Study of RO5186582 Treatment on Cytochrome P450 (CYP) 3A4 Activity in Healthy Participants

Roche

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: RO5186582; Drug: Midazolam, IV; Drug: Midazolam, oral

Study type: Interventional

Funder types: Industry

Identifiers

NCT02254759

WP29393

2014-001850-41 (EudraCT Number)

Details and patient eligibility

About

This is a non-randomized, open-label, five treatment, fixed sequence cross-over study to investigate the effect of RO5186582 treatment on CYP3A activity using midazolam as a probe CYP3A substrate, and also to assess the pharmacodynamic measures of brain electrical activity and sedation to explore the pharmacodynamic interaction between the gama-amino butyric acid (GABA)A negative allosteric modulator RO5186582 and the prototypical GABAA positive allosteric modulator midazolam. The anticipated study duration is up to nine weeks.

Enrollment: 12 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy participants with signed informed consent.

Exclusion criteria

• A history of epilepsy, convulsions or significant head injury
• Significant history of drug allergy, as determined by the Investigator, or a known hypersensitivity to any of the ingredients of any of the study treatments
• Use of any drugs or substances, including herbal treatments such as St John's Wort, that are known to be substrates, inducers or inhibitors of CYP3A4 within 30 days of the first dose administration
• Pregnant or lactating
• Any other clinically relevant abnormalities, concomitant diseases or ongoing medical conditions

Trial design

12 participants in 5 patient groups

IV Midazolam Alone

Other group

Description:

A single 1 milligram (mg) dose of IV Midazolam on Day 1.

Treatment:

Drug: Midazolam, IV

Oral Midazolam Alone

Other group

Description:

A single 5 mg oral dose of midazolam on Day 2.

Treatment:

Drug: Midazolam, oral

RO5186582 Alone

Experimental group

Description:

RO5186582 240 mg oral tablet twice daily (BID) for 14 days from Days 3 to 16.

Treatment:

Drug: RO5186582

RO5186582 Plus IV Midazolam

Experimental group

Description:

RO5186582 240 mg BID oral tablet in combination with a single 1 mg IV dose of midazolam on Day 17.

Treatment:

Drug: Midazolam, IV

Drug: RO5186582

RO5186582 Plus Oral Midazolam

Experimental group

Description:

RO5186582 240 mg BID in combination with a single 5 mg oral dose of midazolam on Day 18.

Treatment:

Drug: RO5186582

Drug: Midazolam, oral