A Study to Assess the Interaction Between ASP1707 and Itraconazole in Healthy Female Subjects

A Phase 1, One Sequence, Cross-over Pharmacokinetic Study to Assess the Interaction Between ASP1707 and Itraconazole, a CYP3A and P-gp Inhibitor in Healthy Female Subjects

The purpose of this study to explore the effect of multiple oral doses of itraconazole on the pharmacokinetics of a single oral dose of ASP1707 in healthy female subjects. This study will also evaluate the safety and tolerability of a single oral dose of ASP1707 alone and in combination with itraconazole.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics; DDI (Drug-Drug Interaction)
• Intervention / Treatment: Drug: itraconazole; Drug: ASP1707

Detailed Description

Subjects will be confined in the clinical unit for up to 15 days.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Parexel International GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female subject must be either of non child bearing potential, post-menopausal prior to screening, or documented surgically sterile. Or, if of childbearing potential, must agree not to try to become pregnant during the study and for 28 days after the final study drug administration, must have a negative urine pregnancy test at Day -1 and, if heterosexually active, agree to consistently use two forms of highly effective form of birth control starting at screening and throughout the study period and for 28 days after the final study drug administration.
• Female subject must not be breastfeeding at screening or during the study period, and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.

Exclusion Criteria:

• Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• Subject uses grapefruit (more than 3x 200 mL) or marmalade (more than three times) in the week prior to admission to the Clinical Unit until ESV, as reported by the subject.
• Subject is a vulnerable subject (e.g., subject kept in detention).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ASP1707 alone	Drug: ASP1707; oral
EXPERIMENTAL: ASP1707 + itraconazole	Drug: itraconazole; oral; Drug: ASP1707; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 with itraconazole: AUCinf	Area under the plasma concentration - time curve from time zero to infinity (AUCinf)	Day 1-15
Pharmacokinetic parameter of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 without itraconazole: AUCinf		Day 1-15
Pharmacokinetic parameter of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 with itraconazole: Cmax	Maximum concentration (Cmax)	Day 1-15
Pharmacokinetic parameter of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 without itraconazole: Cmax		Day 1-15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetics of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 concentration with itraconazole: AUClast, tmax, t1/2, AUCinf (%extrap), tlag, MRT, λz, CL/F, Vz/F, TER and MPR	Area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast), Time to attain Cmax (tmax), apparent terminal elimination half life (t1/2), area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf [%extrap]), absorption lag time (tlag), Mean Residence Time (MRT), terminal elimination rate constant (λz), apparent total systemic clearance (CL/F) (ASP1707 (=R-enantiomer) only), apparent volume of distribution during terminal elimination phase (Vz/F) (ASP1707 only), total exposure ratio (TER) and metabolite-parent ratio (MPR) (AS1948006 only)	Day 1-15
Composite of pharmacokinetics of ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006 concentration without itraconazole: AUClast, tmax, t1/2, AUCinf (%extrap), tlag, MRT, λz, CL/F, Vz/F, TER and MPR	CL/F (ASP1707 (=R-enantiomer) only), Vz/F (ASP1707 only), MPR (AS1948006 only)	Day 1-15
Composite of pharmacokinetics of itraconazole and hydroxy itraconazole concentrations with ASP1707 (=R-enantiomer), AS1948006 and the sum of ASP1707 and AS1948006: AUCtau, tmax, Cmax, MPR (hydroxy itraconazole only), Ctrough	Area under the plasma concentration - time curve between consecutive dosing (AUCtau), plasma concentration at the end of a dosing interval at steady state (Ctrough)	Days 4-15

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (ESTIMATE): June 26, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 3, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Healthy subjects; Itraconazole; ASP1707
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 1707-CL-0030; 2013-005370-21 (EUDRACT_NUMBER)