Breast CancerPhase 1PKNCT02780713

A Study to Assess the Pharmacokinetics and Safety of Different Forms and Formulations of AZD9496 in Healthy Subjects

A Phase 1 study testing AZD9496 (Reference), AZD9496 Variant A and AZD9496 Variant B in people with Breast Cancer, run by AstraZeneca at 1 site in United States.

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 is a phase 1 open label single centre study of AZD9496 administered orally in healthy volunteers. The study design involves single administration of different forms, formulations and doses of AZD9496. The study is designed to investigate these different AZD9496 variants. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Breast Cancer
What is being tested?: AZD9496 (Reference), AZD9496 Variant A and AZD9496 Variant B
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 2 Jun 2016to 20 Sep 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male and/or female subjects aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria: Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the post-menopausal range (OR) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
Male subjects aged 18 to 39 years must be vasectomized. Male subjects aged 40 to 65 years must either be vasectomized or have no intention of fathering a child for a period of 6 months after receiving the last dose of IMP.
Have a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive.
Values for AST, ALT, TBL, GGT and ALP must be at or below the upper limit of normal ranges at screening.

Who cannot join

History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Previous history of venous or arterial thromboembolism or thrombophilia.
History of endometrial polyps, endometrial cancer, atypical endometrial hyperplasia, or other endometrial disorders unless subjects have undergone total hysterectomy and there is no evidence of active disease (females only).
Any clinically significant abnormalities in clinical chemistry (other than Inclusion no.6), hematology, or urinalysis results at screening, as judged by the investigator.

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Any clinically significant abnormal findings in supine vital signs, after 10 minutes of supine rest, at screening and/or admission to the unit, defined as: (a) Systolic blood pressure < 90 mmHg or ≥ 150 mmHg (b) Diastolic blood pressure < 50 mmHg or ≥ 95 mmHg and (c) Heart rate < 45 or > 90 beats per minute
Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG that, as judged by the investigator, that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or pronounced left ventricular hypertrophy.
Prolonged QTcF > 460 ms for females and QTcF > 450 ms for males or family history of long QT syndrome.
PR (PQ) interval shortening < 110 ms or evidence of ventricular pre-excitation).
PR (PQ) interval prolongation > 240 ms, intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block.
Persistent or intermittent complete bundle branch block with QRS > 120 ms or evidence of pronounced ventricular hypertrophy or pre-excitation.
Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody.
Known or suspected history of drug abuse, as judged by the investigator.
Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.
Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as judged by the investigator.
Positive screen for drugs of abuse, alcohol or cotinine at screening or on each admission to the unit.
History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9496.
Excessive intake of caffeine/xanthine containing drinks or food (e.g., coffee, tea, chocolate), as judged by the investigator.
Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life Note: Hormonal replacement therapy is not allowed for females.
Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion is 3 months after the final dose from previous study or 1 month after the last visit of previous study, whichever is the longest. ote: Subjects consented and screened, but not dosed in this study or a previous phase I study, are not excluded.
Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives
Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
Subjects who are vegans or have medical dietary restrictions.
Subjects who cannot communicate reliably with the investigator.
Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Baltimore, Maryland, 21225

Other trials in United States

About this study

Official title: A Phase I Study to Evaluate the Pharmacokinetic and Safety Profile of AZD9496 Following Single Dose Administration of Different Forms and Formulations in Healthy Subjects

This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses.

Read the detailed description

A phase 1, open-label, single centre study to assess the pharmacokinetics, Safety and tolerability of different forms, formulations and doses of AZD9496 in healthy volunteers. This is a fixed sequence study with 5-sequential treatment periods. Each subject will receive 5 single doses of AZD9496 in different forms, formulations and doses.

Treatment period one will assess AZD9496 Variant A: 100mg.
Treatment period two will assess AZD9496 Reference form: 100mg.
Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg.
Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg.
Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: *300mg. *Based on a review of pharmacokinetic and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5.

Conditions: Breast Cancer
Being tested: AZD9496 (Reference), AZD9496 Variant A, AZD9496 Variant B, AZD9496 Variant C, AZD9496 Variant D
Keywords: Breast cancer, Healthy volunteers, Pharmacokinetics, AZD9496, Safety, Tolerability
Medical subject headings: Breast Neoplasms

What participants receive

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

AZD9496 (Reference)Drug
AZD9496 (Reference)
AZD9496 Variant ADrug
AZD9496 Variant A.
AZD9496 Variant BDrug
AZD9496 Variant B
AZD9496 Variant CDrug
AZD9496 Variant C
AZD9496 Variant DDrug
AZD9496 Variant D

Study groups in NCT02780713
Study group	Role	What they receive
AZD9496	Experimental	This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses. 1. Treatment period 1 will assess AZD9496 Variant A: 100mg. 2. Treatment period 2 will assess AZD9496 Reference: 100mg. 3. Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg. 4. Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg. 5. Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: 300mg. Based on a review of PK and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5 Receives: Drug: AZD9496 (Reference); Drug: AZD9496 Variant A; Drug: AZD9496 Variant B; Drug: AZD9496 Variant C; Drug: AZD9496 Variant D

What is being measured

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

Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.
To evaluate maximum observed plasma concentration (Cmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.
Measured: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period
To evaluate the area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC (0-t) of AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation
Measured: Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
To evaluate maximum plasma concentration (Cmax) of capsule variants by comparing with reference AZD9496
Measured: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
To evaluate area under curve from time zero to time with last observation (AUC0-t) of variants by comparing with reference AZD9496
Measured: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
To evaluate area under the curve from time zero to time infinity (AUC 0-infinity) of variants by comparing with reference AZD9496
Measured: Regular Pharmacokinnetic measurement Pre-dose, 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24, and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period
To evaluate area under the curve from time zero to infinity (AUC 0-infinity) for AZD9496 and its metabolites
Measured: Regular pharmacokinetic measurement pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

Secondary outcomes (9)

Time to Reach Maximum Observed Plasma Concentration (Tmax) for AZD9496 and Its Metabolites at Each Treatment Period.
To evaluate time to reach maximum observed plasma concentration (Tmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Effective Half-life ( t½,Eff) for AZD9496 and Its Metabolites at Each Treatment Period
To evaluate effective half-life (t½,eff), for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.
Measured: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Metabolite to Parent Ratios (MRAUC0-t, MRCmax, MRAUC) at Each Treatment Period.
To evaluate metabolite to parent ratios (MRAUC0-t, MRCmax, MRAUC) at each treatment period.
Measured: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: AUC From Time Zero to 12 and 24 Hours Post-dose for AZD9496 and Its Metabolites at Each Treatment Period
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: The Terminal Elimination Half-life (t½,λz) for AZD9496 and Its Metabolites at Each Treatment Period
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Apparent Volume of Distribution (Vss/F) of AZD9496 and Its Metabolites at Each Treatment Period
Measured: Day 1, Day 2, Day 3 and Day 4
Pharmacokinetics: Apparent Oral Clearance (CL/F) of AZD9496 and Its Metabolites at Each Treatment Period
Measured: Day 1, Day 2, Day 3 and Day 4
Pharmacokinetics: Apparent Terminal Elimination Rate Constant (λz) of AZD9496 and Its Metabolites at Each Treatment Period
Measured: Day 1, Day 2, Day 3, Day 4
Pharmacokinetics: Mean Residence Time (MRT) of AZD9496 and Its Metabolites at Each Treatment Period
Measured: Day 1, Day 2, Day 3, Day 4

Timeline

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

2 Jun 201620 Sep 2016

First posted23 May 2016 (estimated)
Study start2 Jun 2016
Primary completion20 Sep 2016
Study completion20 Sep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies 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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02780713
Sponsor's protocol ID: D6090C00005
Acronym: PK
Status last verified: Aug 2021
First submitted: 20 May 2016
Last updated: 25 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study to Evaluate the Pharmacokinetic and Safety Profile of AZD9496 Following Single Dose Administration of Different Forms and Formulations in Healthy Subjects
ClinicalTrials.gov ID: NCT02780713
Acronym / sponsor ID: PK / D6090C00005
Conditions: Breast Cancer
Keywords: Breast cancer, Healthy volunteers, Pharmacokinetics, AZD9496, Safety, Tolerability
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 2 Jun 2016 (actual)
Primary completion: 20 Sep 2016 (actual)
Study completion: 20 Sep 2016 (actual)
First posted: 23 May 2016 (estimated)
Results: Posted 25 Aug 2021

Clinical summary

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

This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses.

Detailed description

Treatment period one will assess AZD9496 Variant A: 100mg.
Treatment period two will assess AZD9496 Reference form: 100mg.
Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg.
Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg.
Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: *300mg. *Based on a review of pharmacokinetic and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5.

Study design

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

Arm	Type	Receives
AZD9496	Experimental	Drug: AZD9496 (Reference), Drug: AZD9496 Variant A, Drug: AZD9496 Variant B, Drug: AZD9496 Variant C, Drug: AZD9496 Variant DThis is a fixed sequence study with 5-sequential treatment periods in healthy volunteers. Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and doses. 1. Treatment period 1 will assess AZD9496 Variant A: 100mg. 2. Treatment period 2 will assess AZD9496 Reference: 100mg. 3. Treatment period 3 will assess one of AZD9496 Variants, B, C or D: 100mg. 4. Treatment period 4 will assess one of AZD9496 Variants, B, C or D: 100mg. 5. Treatment period 5 will assess one of AZD9496 Variants A, B, C or D: 300mg. Based on a review of PK and safety results from Treatment Periods 1, 3 and 4, a lower dose of 200 mg may be administered in Treatment Period 5

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male and/or female subjects aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria: Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the post-menopausal range (OR) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
Male subjects aged 18 to 39 years must be vasectomized. Male subjects aged 40 to 65 years must either be vasectomized or have no intention of fathering a child for a period of 6 months after receiving the last dose of IMP.
Have a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive.

Key exclusion criteria (28 listed)

History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Previous history of venous or arterial thromboembolism or thrombophilia.
History of endometrial polyps, endometrial cancer, atypical endometrial hyperplasia, or other endometrial disorders unless subjects have undergone total hysterectomy and there is no evidence of active disease (females only).

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
AZD9496 (Reference)AZD9496 (Reference)	Drug	AZD9496
AZD9496 Variant AAZD9496 Variant A.	Drug	AZD9496
AZD9496 Variant BAZD9496 Variant B	Drug	AZD9496
AZD9496 Variant CAZD9496 Variant C	Drug	AZD9496
AZD9496 Variant DAZD9496 Variant D	Drug	AZD9496

Primary outcome

Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.
Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate maximum observed plasma concentration (Cmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate the area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC (0-t) of AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation
Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate maximum plasma concentration (Cmax) of capsule variants by comparing with reference AZD9496
Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate area under curve from time zero to time with last observation (AUC0-t) of variants by comparing with reference AZD9496
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Time frame: Regular Pharmacokinnetic measurement Pre-dose, 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24, and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate area under the curve from time zero to time infinity (AUC 0-infinity) of variants by comparing with reference AZD9496
Pharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period
Time frame: Regular pharmacokinetic measurement pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
To evaluate area under the curve from time zero to infinity (AUC 0-infinity) for AZD9496 and its metabolites

9 secondary outcomes

Time to Reach Maximum Observed Plasma Concentration (Tmax) for AZD9496 and Its Metabolites at Each Treatment Period.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Effective Half-life ( t½,Eff) for AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Metabolite to Parent Ratios (MRAUC0-t, MRCmax, MRAUC) at Each Treatment Period.
Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: AUC From Time Zero to 12 and 24 Hours Post-dose for AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: The Terminal Elimination Half-life (t½,λz) for AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period
Pharmacokinetics: Apparent Volume of Distribution (Vss/F) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Day 1, Day 2, Day 3 and Day 4
Pharmacokinetics: Apparent Oral Clearance (CL/F) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Day 1, Day 2, Day 3 and Day 4
Pharmacokinetics: Apparent Terminal Elimination Rate Constant (λz) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Day 1, Day 2, Day 3, Day 4
Pharmacokinetics: Mean Residence Time (MRT) of AZD9496 and Its Metabolites at Each Treatment Period
Time frame: Day 1, Day 2, Day 3, Day 4

Results and safety

Results posted to the registry on 25 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Period 1	14	14
Treatment Period 2	0	0
Treatment Period 3	0	0
Treatment Period 4	0	0
Treatment Period 5	0	0

Primary outcome: Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.

Time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Treatment Period 1 n = 14	Treatment Period 2 n = 14	Treatment Period 3 n = 12	Treatment Period 4 n = 12	Treatment Period 5 n = 12
AZD9496	64.85 (73.54)	381.0 (55.83)	138.2 (75.35)	91.83 (52.13)	550.9 (41.85)
M3	10.30 (98.93)	62.98 (76.91)	23.56 (74.30)	14.47 (39.01)	98.72 (54.80)
M5	1.102 (85.27)	7.409 (75.18)	2.454 (80.35)	1.520 (42.67)	11.71 (49.60)

Population analysed: Safety set with 1 primary PK parameter for AZD9496 calculable for Treatment Period 2 and 1 other period. For AUC 0-inf, a predefined R2adj \>0.8 (the goodness of fit parameter for regression estimate of elimination rate constant lambda z used in the AUC 0-inf calculation) was used to determine if the individual AUC estimate was reportable.

Primary outcome: Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period

Time frame: Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Treatment Period 1 n = 14	Treatment Period 2 n = 14	Treatment Period 3 n = 12	Treatment Period 4 n = 12	Treatment Period 5 n = 12
AZD9496	383.4 (60.54)	1207 (53.01)	677.8 (50.08)	523.0 (26.77)	2322 (32.12)
M3	46.71 (124.65)	196.6 (80.92)	111.7 (62.00)	78.23 (65.96)	411.3 (57.56)
M5	4.872 (98.91)	23.11 (73.68)	11.05 (62.20)	7.614 (57.93)	46.42 (49.23)

Primary outcome: Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

Measure	DN Ratio - Variant A (100 mg): Ref (100 mg) n = 14	DN Ratio - Variant B (100 mg) : Ref (100 mg) n = 12	DN Ratio - Variant C (100 mg) : Ref (100 mg) n = 12
Value	0.1702 (90.94)	0.3440 (110.40)	0.2285 (89.40)

DN Ratio - Variant A (100 mg): Ref (100 mg): Percentage: 17.02 (95% CI 11.79 to 24.58)
DN Ratio - Variant B (100 mg) : Ref (100 mg): Percentage: 36.28 (95% CI 23.84 to 55.20)
DN Ratio - Variant C (100 mg) : Ref (100 mg): Percentage: 24.10 (95% CI 16.84 to 34.48)

Primary outcome: Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference

Measure	DN Ratio - Variant A (100 mg): Ref (100 mg) n = 14	DN Ratio - Variant B (100 mg) : Ref (100 mg) n = 12	AZD9496 - Variant C (100 mg) n = 12
Value	0.3175 (46.35)	0.5227 (50.95)	0.4033 (33.15)

DN Ratio - Variant A (100 mg): Ref (100 mg): Percentage: 31.75 (95% CI 25.77 to 39.12)
DN Ratio - Variant B (100 mg) : Ref (100 mg): Percentage: 54.17 (95% CI 42.16 to 69.60)
AZD9496 - Variant C (100 mg): Pecentage: 41.23 (95% CI 34.79 to 48.86)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: From enrollment until the final follow-up visit (5 to 7 days after last dose). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Period 1	0 of 14 (0%)	2 of 14 (14.3%)	0 of 14
Treatment Period 2	0 of 14 (0%)	1 of 14 (7.1%)	0 of 14
Treatment Period 3	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Treatment Period 4	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Treatment Period 5	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
All Participants	0 of 14 (0%)	5 of 14 (35.7%)	0 of 14

Limitations and caveats (from the sponsor): Data from all analysed secondary pharmacokinetic parameters are presented.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Dr. Ronald Goldwater principal investigator

Parexel

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD9496 (Reference), AZD9496 Variant A and AZD9496 Variant B in people with Breast Cancer, run by AstraZeneca at 1 site in United States.

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 28 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 25 Aug 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 United States. 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?

Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period. (time frame: Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period). The study lists 6 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 NCT02780713.

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 25 Aug 2021.