A Study to Assess How Itraconazole Affects the Uptake and Elimination of Capivasertib in the Body

An Open-label, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of Capivasertib When Administered Alone and In Combination With Itraconazole

This study will be an open-label, fixed sequence study in healthy subjects (vasectomized males and females of non-childbearing potential), performed at a single study centre.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)
• Intervention / Treatment: Drug: Capivasertib; Drug: Itraconazole

Detailed Description

The study will comprise:

• A screening period of maximum 21 days;
• A fixed sequence of 3 treatment periods: Treatment Period 1: Capivasertib only, Treatment Period 2: Itraconazole pre-treatment (run-in) period, and Treatment Period 3: Capivasertib and itraconazole in combination.
• A Follow-up Visit at 7 to 14 days after the last capivasertib PK sample in Treatment Period 3.

There will be no washout between Treatment Period 2 and Treatment Period 3. Each subject will be involved in the study for up to 7 weeks.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female subjects aged 18 to 58 years with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the study centre, must not be lactating and must be of non-childbearing potential, confirmed at screening.
• Male subjects must be vasectomized (at least 6 months prior to the Screening Visit), with documented post-procedural medical assessment of surgical success.
• Have a body mass index between 18 and 28 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Non-smoker, defined as a subject who has not smoked previously or who has discontinued smoking or the use of other nicotine/nicotine-containing products.

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs; abnormalities in haematology, clinical chemistry, or urinalysis results, at screening or on admission to the study centre, as judged by the Investigator.
• Any clinically significant abnormalities in glucose metabolism, blood lipid profiles , liver enzymes , vital signs , and 12-lead electrocardiogram.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg) or antibody to hepatitis B core antigen (anti-HBc), hepatitis C antibody (anti-HCV), and human immunodeficiency virus (HIV) antibody.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator.
• Positive screen for drugs of abuse, alcohol and/or cotinine at screening or on admission to the study centre.
• Subjects who have previously received capivasertib.
• Subject has a positive test result for Severe acute respiratory syndrome (SARS)-Coronavirus (CoV)-2 Reverse Transcriptase (RT)-Polymerase Chain Reaction (PCR) before randomization.
• Subject has clinical signs and symptoms consistent with corona virus disease 2019 (COVID-19) (e.g., fever, dry cough, dyspnoea, sore throat, anosmia/hyposmia, loss or reduced taste, and fatigue) or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
• Subjects who are regularly exposed to the risk of COVID-19 infection as part of their daily life (e.g., health care professionals working in COVID-19 wards or at emergency departments).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capivasertib + Itraconazole; Subjects will receive a single oral dose of capivasertib on Day 1 during treatment period 1, itraconazole on Days 3, 4, and 5 during treatment period 2, and single oral dose of capivasertib plus a dose of itraconazole on Day 6, followed by itraconazole alone on Day 7 during treatment period 3.	Drug: Capivasertib; Subects will be administered single doses of capiversatib on Day 1 and Day 6.; Drug: Itraconazole; Subjects will be administered itraconazole twice daily on Day 3, followed by once daily doses in the morning for 4 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib	Assessment of AUCinf of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Maximum observed plasma (peak) drug concentration (Cmax) of capivasertib	Assessment of Cmax of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) of capivasertib and its major metabolite (AZ14102143)	Assessment of AUClast of capivasertib and its major metabolite (AZ14102143).	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Time delay between drug administration and the first observed concentration in plasma (tlag) of capivasertib	Assessment of tlag of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of capivasertib and its major metabolite (AZ14102143)	Assessment of tmax of capivasertib and its major metabolite (AZ14102143).	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration time curve (t½λz) of capivasertib and its major metabolite (AZ14102143)	Assessment of t½λz of capivasertib and its major metabolite (AZ14102143).	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Terminal elimination rate constant (λz) of capivasertib and its major metabolite (AZ14102143)	Assessment of λz of capivasertib and its major metabolite (AZ14102143).	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of capivasertib	Assessment of CL/F of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Volume of distribution (apparent) at steady state following extravascular administration (Vz/F) (based on terminal phase) of capivasertib	Assessment of Vz/F of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
AUCinf of major metabolite (AZ14102143) of capivasertib	Assessment of AUCinf of major metabolite (AZ14102143) of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Cmax of major metabolite (AZ14102143) of capivasertib	Assessment of Cmax of major metabolite (AZ14102143) of capivasertib.	Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours after capivasertib dose on Day 1 and Day 6
Number of subjects with serious and non-serious adverse events	Assessment of safety and tolerability of capivasertib alone and in combination with itraconazole.	From Screening until Follow-upVisit / Early Termination (7-14 days after last PK sample)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel
• Investigators: Principal Investigator: Rainard Fuhr, Dr., Parexel

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): March 25, 2021
• Study Completion (Actual): March 25, 2021

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Itraconazole; Drug-Drug Interaction; Capivasertib; Protein kinase inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; 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: D3614C00004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No