Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)Phase 1NCT04712396

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

A Phase 1 study testing Capivasertib and Itraconazole in people with Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer), run by AstraZeneca at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 58 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)
What is being tested?: Capivasertib and Itraconazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteGermany
Study dates: 1 Feb 2021to 25 Mar 2021
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 58 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Show all 10Show fewer

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).

Trial locations and contacts

1 site in 1 country.

Germany1 site

Research Site
Berlin, 14050

Other trials in Germany

About this study

Official title: 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.

Read the 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.

Conditions: Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)
Being tested: Capivasertib, Itraconazole
Keywords: Drug-Drug Interaction, Protein kinase inhibitor, Capivasertib, Itraconazole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CapivasertibDrug
Subects will be administered single doses of capiversatib on Day 1 and Day 6.
ItraconazoleDrug
Subjects will be administered itraconazole twice daily on Day 3, followed by once daily doses in the morning for 4 days.

Study groups in NCT04712396
Study group	Role	What they receive
Capivasertib + Itraconazole	Experimental	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. Receives: Drug: Capivasertib; Drug: Itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib
Assessment of AUCinf of capivasertib.
Measured: 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.
Measured: 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 outcomes (10)

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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Screening until Follow-upVisit / Early Termination (7-14 days after last PK sample)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 202125 Mar 2021

First posted15 Jan 2021
Study start1 Feb 2021
Primary completion25 Mar 2021
Study completion25 Mar 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04712396
Sponsor's protocol ID: D3614C00004
Status last verified: Apr 2021
First submitted: 15 Dec 2020
Last updated: 9 Apr 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of Capivasertib When Administered Alone and In Combination With Itraconazole
ClinicalTrials.gov ID: NCT04712396
Acronym / sponsor ID: D3614C00004
Conditions: Healthy Volunteers (Intended Indication: Metastatic Patients With Triple Negative or HR+ Breast Cancer, or Hormone Sensitive Prostate Cancer)
Keywords: Drug-Drug Interaction, Protein kinase inhibitor, Capivasertib, Itraconazole
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 1 Feb 2021 (actual)
Primary completion: 25 Mar 2021 (actual)
Study completion: 25 Mar 2021 (actual)
First posted: 15 Jan 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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 design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Capivasertib + Itraconazole	Experimental	Drug: Capivasertib, Drug: ItraconazoleSubjects 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.

Who may qualify

Ages: 18 to 58 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CapivasertibSubects will be administered single doses of capiversatib on Day 1 and Day 6.	Drug	Capivasertib + Itraconazole
ItraconazoleSubjects will be administered itraconazole twice daily on Day 3, followed by once daily doses in the morning for 4 days.	Drug	Capivasertib + Itraconazole

Primary outcome

Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib
Time frame: 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
Assessment of AUCinf of capivasertib.
Maximum observed plasma (peak) drug concentration (Cmax) of capivasertib
Time frame: 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
Assessment of Cmax of capivasertib.

10 secondary outcomes

Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) of capivasertib and its major metabolite (AZ14102143)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Screening until Follow-upVisit / Early Termination (7-14 days after last PK sample)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rainard Fuhr, Dr. principal investigator

Parexel

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under plasma concentration-time curve from zero to infinity (AUCinf) of capivasertib (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04712396.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2021.