NCT03204578

Physiological Study of the Human CYP3A Activity (PiSA)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Investigator-initiated physiological study to characterize the function of a major drug metabolizing enzyme using a microdosed phenotyping probe to avoid unwanted, concentration-dependent effects.

Detailed description

Disposition of a drug depends on absorption, distribution, metabolism, and elimination (ADME). Quantifying the ADME capacity of a patient may help to individualize target exposure by choosing the corresponding dose required for this individual. The large group of drugs eliminated by members of the CYP3A isozyme subfamily accounts for about 50% of all marketed drugs. Co-medication can modulate CYP3A activity 400-fold either by inducing isozyme expression or inhibiting expressed enzyme. Therefore, due to the variability of CYP3A activity, dose requirements of CYP3A substrates vary considerably between individual patients and may even rapidly vary within a patient. There is clinical interest in using CYP3A activity as a biomarker to predict optimal CYP3A drug dosing, improve therapeutic efficacy, and minimize adverse drug effects. Determination of CYP3A activity is usually done with oral midazolam doses of 2-7.5 mg (phenotyping). Because therapeutic doses have pharmacological effects and can cause sedation, especially if CYP3A is inhibited, a microdosing approach for CYP phenotyping was developed to avoid any pharmacological activity. Oral midazolam pharmacokinetics are linear over a 30,000-fold range and 300 ng doses can reliably predict drug interactions with strong CYP3A inhibitors like ketoconazole. The primary objective of this trial is to determine CYP3A activity using microdosed midazolam delivered from an oral disintegrating formulation in comparison to an oral midazolam solution. The oral disintegrating formulation is an innovative application form that would facilitate administration of the phenotyping probe in special patient populations.

Conditions

• Cytochrome P450 CYP3A Enzyme Deficiency

Interventions

Type	Name	Description
DRUG	AB (Midazolam OD formulation/Dormicum)	Oral disintegrating formulation (Midazolam OD Formulation). The Midazolam OD Formulation was developed by Kyukyu Pharmaceutical Co., Ltd
DRUG	BA (Dormicum/Midazolam OD formulation)	Oral disintegrating film (Midazolam OD Formulation). The Midazolam OD Formulation was developed by Kyukyu Pharmaceutical Co., Ltd

Timeline

• Start date: 2017-08-18
• Primary completion: 2017-09-25
• Completion: 2017-09-25
• First posted: 2017-07-02
• Last updated: 2018-04-18

Locations

1 site across 1 country: Switzerland