Physiological Study of the Human CYP3A Activity (PiSA)

NCT03204578 | Completed Phase 4

• 2 other identifiers: 2017-00545me16Haschke
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cytochrome P450 CYP3A Enzyme Deficiency

Outcome Measures

Primary Outcomes (1)

• AUC0-12 of midazolam in plasma

  Midazolam OD Formulation was developed by Kyukyu Pharmaceutical Co., Ltd. and is provided free of charge in support of the present study.

  0,1,2,3,4,5,6,7,8,9,10,11,12 hours

Secondary Outcomes (1)

• Cmax of midazolam in plasma

  0,1,2,3,4,5,6,7,8,9,10,11,12 hours

Study Arms (2)

AB (Midazolam OD/Dormicum)

EXPERIMENTAL

Subjects with sequence AB will first receive the Intervention OD formulation (Period A, 30 µg Midazolam) and at the second visit the oral solution (Period B, 30 µg Dormicum ).

Drug: AB (Midazolam OD formulation/Dormicum)

BA (Dormicum/midazolam OD)

EXPERIMENTAL

Subjects with sequence BA will first receive the Intervention oral solution (Period B, 30 µg Dormicum) and at the second visit the OD disintegrating formulation (Period A, 30 µg Midazolam).

Drug: BA (Dormicum/Midazolam OD formulation)

Interventions

AB (Midazolam OD formulation/Dormicum) DRUG

Oral disintegrating formulation (Midazolam OD Formulation). The Midazolam OD Formulation was developed by Kyukyu Pharmaceutical Co., Ltd

Also known as: oral disintegrating (OD) formulation containing midazolam

AB (Midazolam OD/Dormicum)

BA (Dormicum/Midazolam OD formulation) DRUG

Oral disintegrating film (Midazolam OD Formulation). The Midazolam OD Formulation was developed by Kyukyu Pharmaceutical Co., Ltd

Also known as: oral disintegrating (OD) formulation containing midazolam

BA (Dormicum/midazolam OD)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects, age of 18 to 50 years, body mass index (BMI) of 18.0 to 29.9 kg/m2

You may not qualify if:

• Any intake of a substance known to induce or inhibit drug metabolising enzymes or transport system enzymes within a period of less than 10 times the respective elimination half-life or 3 weeks (whatever is longer).
• History or clinical evidence of any disease or medical condition, which may interfere with the pharmacokinetics of midazolam or which may increase the risk for toxicity or adverse events.
• Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel,

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (1)

• Kiene K, Hayasi N, Burhenne J, Uchitomi R, Sunderhauf C, Schmid Y, Haschke M, Haefeli WE, Krahenbuhl S, Mikus G, Inada H, Huwyler J. Microdosed midazolam for the determination of cytochrome P450 3A activity: Development and clinical evaluation of a buccal film. Eur J Pharm Sci. 2019 Jul 1;135:77-82. doi: 10.1016/j.ejps.2019.05.010. Epub 2019 May 16.

  PMID: 31102650 DERIVED

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephan Krähenbühl

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, randomised, single-dose crossover design

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: July 2, 2017
• Study Start: August 18, 2017
• Primary Completion: September 25, 2017
• Study Completion: September 25, 2017
• Last Updated: April 18, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)