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

Phase 1
Completed
Conditions
Healthy Patient Study
Interventions
Registration Number
NCT02470832
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Combination therapy RG1662 + itraconazoleRG1662Days 20-29: Oral administration RG1662 twice daily within 30 minutes of a meal + 2 x 100 mg itraconazole once daily with food
Combination therapy RG1662 + itraconazoleitraconazoleDays 20-29: Oral administration RG1662 twice daily within 30 minutes of a meal + 2 x 100 mg itraconazole once daily with food
RG1662 MonotherapyRG1662Days 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.)
itraconazole MonotherapyitraconazoleDays 15-19: 200 mg of itraconazole twice daily for 5 days (Days 15 to 18, Day 19 only a.m. dose)
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Clinically significant changes from baseline in physical examination or laboratory parametersWithin 29 days
Change from baseline in QTcFUp to 29 days
Incidence of adverse eventsWithin 43 days
Mean model parameters of RG1662 concentration vs. QTcF changesWithin 29 days
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