A Study to Investigate the Effect of CYP3A Inhibition on the Pharmacokinetics of RG1662 in Healthy Subjects

Study Overview
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Brief Summary
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The study is being conducted to investigate the effect of itraconazole treatment in the pharmacokinetics of RG1662. It is also to evaluate the exposure of RG1662 vs. QTc response relationship and the safety and tolerability of RG1662 when given in combination with itraconazole in healthy subjects.

Conditions
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Healthy Patient Study

Intervention / Treatment
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* Drug: RG1662
* Drug: itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers Ages 18 to 60 years, inclusive A body mass index (BMI) between 18 to 32 kg/m2, inclusive Agreement to comply with study restrictions Exclusion Criteria: History of epilepsy, convulsions or significant head injury or electroencephalogram (EEG) abnormalities Electrocardiogram (EGC) or vital signs abnormalities 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination therapy RG1662 + itraconazole<br>Days 20-29: Oral administration RG1662 twice daily within 30 minutes of a meal + 2 x 100 mg itraconazole once daily with food | Drug: RG1662<br> <br> Drug: itraconazole<br> <br> |
| Experimental: RG1662 Monotherapy<br>Days 1-10: RG1662 120 mg twice daily (b.i.d.) within 30 minutes of a meal for 10 days (Days 1 to 9, Day 10 only a.m. dose). (Cohort A subjects will receive 1 x 120 mg RG1662 tablets twice daily. In Cohorts B and C the dose of RG1662 will be decided upon following review of the interim safety and pharmacokinetic data of the 4 subjects in Cohort A.) | Drug: RG1662<br> <br> |
| Experimental: itraconazole Monotherapy<br>Days 15-19: 200 mg of itraconazole twice daily for 5 days (Days 15 to 18, Day 19 only a.m. dose) | Drug: itraconazole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from 0-t (AUC0-t) |  | Within 29 days | 
| Maximum observed plasma concentration (Cmax) |  | Within 29 days | 
| Time to maximum observed plasma concentration (Tmax) |  | Within 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in QTcF |  | Up to 29 days | 
| Incidence of adverse events |  | Within 43 days | 
| Clinically significant changes from baseline in physical examination or laboratory parameters |  | Within 29 days | 
| Mean model parameters of RG1662 concentration vs. QTcF changes |  | Within 29 days |