OncologyPhase 1NCT02491944
A Phase I, Open-label Study to Assess Bioavailability of a Single Oral Dose of AZD9291 vs an IV Dose of [14C]AZD9291
A Phase 1 study testing AZD9291 and [14C]AZD9291 in people with Oncology, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
The Sponsor is developing the study drug, AZD9291, for the potential treatment of nonsmall cell lung cancer. Lung cancer has been the most common cancer in the world for several decades and represents 12.8% of all new cancer cases in 2008. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Oncology
- What is being tested?
- AZD9291 and [14C]AZD9291
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2015to Aug 2015
- 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
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed dated, written informed consent.
- Healthy male aged 18 to 65 yrs with suitable veins for blood sampling
- BMI: 19 and 32 kg/m2 inclusive, weight at least 50 kg and no more than 100 kg, inclusive.
- At screening, calculated creatinine clearance ≥50 mL/min using Cockcroft Gault formula.
- Willing to use defined methods of contraception
- Willing and able to comply with study procedures, restrictions and requirements.
- Provision of informed consent for genetic research. Declining genetic research will not exclude subjects from other aspects of study.
Who cannot join
- Involvement in planning and/or conduct of study.
- Subjects previously enrolled in this study.
- History of clinically significant disease or disorder which, either puts subject at risk because of participation in study, or influences results or subject's ability to participate in study.
- History or presence of condition known to interfere with ADME of drugs.
- Any clinically significant abnormalities in physical examination, as judged by PI.
- Acute illness, surgical procedures, or trauma from within 2 wks before screening until first admin of investigational product (IMP).
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- Subjects who have received live or live-attenuated vaccine in 2 wks prior to IMP admin.
- Subjects with active malignancy or neoplastic disease in previous 12 mths.
- A suspected/manifested infection according to IATA Categories A and B.
- Positive screening tests for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting 12-lead ECG, QT interval >470 ms.
- Known or suspected history of significant drug abuse.
- Positive screen for drugs of abuse or cotinine at screening or positive screen for alcohol, drugs of abuse, or cotinine on admission to centre prior to first admin of IMP.
- History of alcohol abuse or excessive intake of alcohol, defined as regular weekly intake of more than 21 units of alcohol in men
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by PI, or history of hypersensitivity to AZD9291, its excipients, or drugs with a similar chemical structure or class.
- Use of any prescribed or non-prescribed medication, including drugs during the 4 wks (or longer depending on the medication's half-life) prior to admin of AZD9291 is not permitted. Occasional use of paracetamol and adrenergic nasal spray for relief of nasal congestion is permitted at the discretion of the PI. Exceptions as agreed by PI and sponsor's medical monitor if do not interfere with aims of study.
- Use of drugs with enzyme inducing properties such as St John's Wort within 4 wks prior to IMP administration.
- Any intake of grapefruit, grapefruit juice, Seville oranges or products containing these fruit within 7 days of first admin of IMP.
- Blood donation within 1 mth of screening or any blood donation/blood loss greater than 500 mL during 3 mths prior to screening.
- Subjects who received another NCE or participated in any other clinical study (including methodology studies where no drugs were given) within 3 mths of first admin of IMP
- Judgment by PI that subject should not participate in study if subject is considered unlikely to comply with study procedures, restrictions, and requirements.
- Ongoing or planned inpatient surgery, dental procedure, or hospitalisation during study
- Radiation exposure exceeding 5 mSv in last 12 mths or 10 mSv in last 5 yrs.
- Admin of any amount of a [14C]-labelled compound within last 12 mths.
- Used of nicotine products (including cigarettes) within previous 3 mths.
- Judgment by PI that subject would not be able to understand or cooperate with requirements of study.
- Previous bone marrow transplant
- Blood transfusion within 120 days of genetic sample collection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-label, Single Dose, Single-Centre Study to Assess the Absolute Bioavailability of a Single Oral Dose of AZD9291 With Respect to an Intravenous Microdose of [14C]AZD9291 in Healthy Male Subjects
The Sponsor is developing the study drug, AZD9291, for the potential treatment of nonsmall cell lung cancer. Lung cancer has been the most common cancer in the world for several decades and represents 12.8% of all new cancer cases in 2008.
The purpose of this study is to see how much AZD9291 is taken up by the body when dosed by mouth (tablet) compared to when the study drug is dosed once by injection directly into the vein (intravenously). The dose given directly into the vein will be radiolabelled. This means that the test drug has a radioactive component which helps us to track where the drug is in the body. This allows us to detect the differences between the tablet and the intravenous dose.
The study will be performed in 12 healthy male subjects aged 18-65 years. On Day 1, subjects will be dosed with a single oral dose of 80 milligrams AZD9291 tablet followed by 100 micrograms [14C] AZD9291 dosed as an intravenous microdose beginning 5 hours and 45 minutes after the oral dose has been administered. Subjects will remain in the study centre until after the 120 hour post-dose blood sample is obtained and will return to the clinic for further visits on Day 8, 10, 15 and 22 for pharmacokinetic and safety assessments.
Read the detailed description
The study is a Phase I, open label, single dose, single centre study performed in 12 healthy male subjects aged 18 to 65 years, inclusive. This study will assess the absolute bioavailability of AZD9291 and evaluate the PK parameters following a single oral dose of AZD9291 and a radiolabelled IV microdose of AZD9291 in healthy male subjects. Oral AZD9291and [14C] AZD9291 intravenous solution are referred to as the investigational products in this study.
A screening visit (Visit 1) to assess the eligibility of the healthy male subjects will occur within 28 days of the administration of the investigational product. Screening assessments will include evaluation of opthalmological assessments, clinical chemistry, haematology, urinalysis, a physical examination, vital signs, 12-lead electrocardiograms (ECGs), medical and surgical history, screening for drugs of abuse, alcohol, hepatitis B and C, and HIV, and recording of concomitant medications and Adverse Events. Study related procedures will only be performed after signing of the Informed Consent Form.
The healthy male subjects will be admitted to the study centre the day before administration of the investigational product (Day 1; Visit 2). On Day 1 (Visit 2), subjects will be dosed with a single oral dose of 80 mg AZD9291 tablet followed by 100 μg [14C] AZD9291 dosed as an IV microdose beginning 5 hours and 45 minutes after the oral dose has been administered. The IV microdose will be infused over 15 minutes and the end of the infusion will be co incidental with median oral tmax (ie, estimated tmax is 6 hours).
The subjects will remain in the study centre until the 120 hour post dose PK blood sample is obtained. Ambulatory visits will occur on Days 8 (Visit 3), 10 (Visit 4), 15 (Visit 5) and 22 (Visit 6) for PK and safety assessments. A follow up visit (Visit 7) will occur 21 to 28 days after discharge (Days 27 - 34) from the study centre and will include routine safety assessments.
- Conditions
- Oncology
- Being tested
- AZD9291, [14C]AZD9291
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291Drug
Single oral dose of 80 mg AZD9291 tablet on Day 1 administered orally with 240 mL water following an overnight fast.
[14C]AZD9291Drug
Each healthy male subject will also receive a single, radiolabeled, 100 μg dose of [14C] AZD9291 administered as an IV microdose infusion starting at 5 hours and 45 minutes after receiving the oral dose.
| Study group | Role | What they receive |
|---|---|---|
| Bioavailability of AZD9291 | Experimental | To assess the absolute bioavailability of a single oral dose of AZD9291 with respect to an intravenous microdose of [14C]AZD9291 Receives: Drug: AZD9291; Drug: [14C]AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Oral Bioavailability
Absolute bioavailability of AZD9291 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD9291 / AUC of the IV dose of [14C]AZD9291 x IV dose/Oral dose x 100
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 5:45, 5:52, 6, 6:05, 6:10, 6:20, 6:25, 6:30, 7, 8, 9, 10, 12, 14, 16, 18, 24, 30, 48, 72, 120, 168, 216, 336 and 504 hours relative to the oral dose.
Secondary outcomes (16)
AUC for AZD9291 and it's Metabolites AZ5104 and AZ7550
Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from zero to infinity for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-24) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 24 hours (AUC 0-24) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-120) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 120 hours (AUC 0-120) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-t) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Pharmacokinetic (PK) profile of the oral dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to the last quantifiable concentration (AUC 0-t) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
Cmax for AZD9291 and it's Metabolites AZ5104 and AZ7550
PK profile of the oral dose of AZD9291 in terms of the maximum observed plasma concentration (Cmax) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
Tmax for AZD9291 and it's Metabolites AZ5104 and AZ7550
PK profile of the oral dose of AZD9291 in terms of the time to maximum observed plasma concentration (Tmax) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
t1/2,λz for AZD9291 and it's Metabolites AZ5104 and AZ7550
PK profile of the oral dose of AZD9291 in terms of the elimination half life (t1/2,λz) for AZD9291 and it's metabolites AZ5104 and AZ7550.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
CL/F for AZD9291
PK profile of the oral dose of AZD9291 in terms of apparent total body clearance of drug from plasma after extravascular administration(CL/F) for AZD9291.
Measured: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from zero to infinity for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-24) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 24 hours (AUC 0-24) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-120) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to 120 hours (AUC 0-120) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-t) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of Area under the plasma concentration - time curve (AUC) from time zero to the last quantifiable concentration (AUC 0-t) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Cmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the maximum observed plasma concentration (Cmax) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Tmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the the time to maximum observed plasma concentration (Tmax) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
t1/2,λz for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of the elimination half life (t1/2,λz) for [14C]AZD9291 and it's metabolites [14C]AZ5104 and [14C]AZ7550.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
CL for [14C]AZD9291
Pharmacokinetic (PK) profile of the IV dose of AZD9291 in terms of total body clearance of drug from plasma after intravascular administration (CL) for [14C]AZD9291.
Measured: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionAug 2015
- Study completionAug 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OncologyStudies 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joanne Collier, MBChB, FFPM, Dip Stats (OU), Principal investigator, Quotient Clinical Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491944
- Sponsor's protocol ID
- D5160C00020
- Status last verified
- Aug 2016
- First submitted
- 3 Jul 2015
- Last updated
- 13 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Vishwanathan K, So K, Thomas K, Bramley A, English S, Collier J. Absolute Bioavailability of Osimertinib in Healthy Adults. Clin Pharmacol Drug Dev. 2019 Feb;8(2):198-207. doi: 10.1002/cpdd.467. Epub 2018 Apr 23.
PubMed 29683562
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Single Dose, Single-Centre Study to Assess the Absolute Bioavailability of a Single Oral Dose of AZD9291 With Respect to an Intravenous Microdose of [14C]AZD9291 in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02491944
- Acronym / sponsor ID
- D5160C00020
- Conditions
- Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Jul 2015
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 8 Jul 2015 (estimated)
- Results
- Posted 13 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Sponsor is developing the study drug, AZD9291, for the potential treatment of nonsmall cell lung cancer. Lung cancer has been the most common cancer in the world for several decades and represents 12.8% of all new cancer cases in 2008.
The purpose of this study is to see how much AZD9291 is taken up by the body when dosed by mouth (tablet) compared to when the study drug is dosed once by injection directly into the vein (intravenously). The dose given directly into the vein will be radiolabelled. This means that the test drug has a radioactive component which helps us to track where the drug is in the body. This allows us to detect the differences between the tablet and the intravenous dose.
The study will be performed in 12 healthy male subjects aged 18-65 years. On Day 1, subjects will be dosed with a single oral dose of 80 milligrams AZD9291 tablet followed by 100 micrograms [14C] AZD9291 dosed as an intravenous microdose beginning 5 hours and 45 minutes after the oral dose has been administered. Subjects will remain in the study centre until after the 120 hour post-dose blood sample is obtained and will return to the clinic for further visits on Day 8, 10, 15 and 22 for pharmacokinetic and safety assessments.
Detailed description
The study is a Phase I, open label, single dose, single centre study performed in 12 healthy male subjects aged 18 to 65 years, inclusive. This study will assess the absolute bioavailability of AZD9291 and evaluate the PK parameters following a single oral dose of AZD9291 and a radiolabelled IV microdose of AZD9291 in healthy male subjects. Oral AZD9291and [14C] AZD9291 intravenous solution are referred to as the investigational products in this study.
A screening visit (Visit 1) to assess the eligibility of the healthy male subjects will occur within 28 days of the administration of the investigational product. Screening assessments will include evaluation of opthalmological assessments, clinical chemistry, haematology, urinalysis, a physical examination, vital signs, 12-lead electrocardiograms (ECGs), medical and surgical history, screening for drugs of abuse, alcohol, hepatitis B and C, and HIV, and recording of concomitant medications and Adverse Events. Study related procedures will only be performed after signing of the Informed Consent Form.
The healthy male subjects will be admitted to the study centre the day before administration of the investigational product (Day 1; Visit 2). On Day 1 (Visit 2), subjects will be dosed with a single oral dose of 80 mg AZD9291 tablet followed by 100 μg [14C] AZD9291 dosed as an IV microdose beginning 5 hours and 45 minutes after the oral dose has been administered. The IV microdose will be infused over 15 minutes and the end of the infusion will be co incidental with median oral tmax (ie, estimated tmax is 6 hours).
The subjects will remain in the study centre until the 120 hour post dose PK blood sample is obtained. Ambulatory visits will occur on Days 8 (Visit 3), 10 (Visit 4), 15 (Visit 5) and 22 (Visit 6) for PK and safety assessments. A follow up visit (Visit 7) will occur 21 to 28 days after discharge (Days 27 - 34) from the study centre and will include routine safety assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bioavailability of AZD9291 | Experimental | Drug: AZD9291, Drug: [14C]AZD9291To assess the absolute bioavailability of a single oral dose of AZD9291 with respect to an intravenous microdose of [14C]AZD9291 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed dated, written informed consent.
- Healthy male aged 18 to 65 yrs with suitable veins for blood sampling
- BMI: 19 and 32 kg/m2 inclusive, weight at least 50 kg and no more than 100 kg, inclusive.
- At screening, calculated creatinine clearance ≥50 mL/min using Cockcroft Gault formula.
- Willing to use defined methods of contraception
Key exclusion criteria (28 listed)
- Involvement in planning and/or conduct of study.
- Subjects previously enrolled in this study.
- History of clinically significant disease or disorder which, either puts subject at risk because of participation in study, or influences results or subject's ability to participate in study.
- History or presence of condition known to interfere with ADME of drugs.
- Any clinically significant abnormalities in physical examination, as judged by PI.
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 |
|---|---|---|
| AZD9291Single oral dose of 80 mg AZD9291 tablet on Day 1 administered orally with 240 mL water following an overnight fast. | Drug | Bioavailability of AZD9291 |
| [14C]AZD9291Each healthy male subject will also receive a single, radiolabeled, 100 μg dose of [14C] AZD9291 administered as an IV microdose infusion starting at 5 hours and 45 minutes after receiving the oral dose. | Drug | Bioavailability of AZD9291 |
Primary outcome
Absolute Oral Bioavailability
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 5:45, 5:52, 6, 6:05, 6:10, 6:20, 6:25, 6:30, 7, 8, 9, 10, 12, 14, 16, 18, 24, 30, 48, 72, 120, 168, 216, 336 and 504 hours relative to the oral dose.
Absolute bioavailability of AZD9291 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD9291 / AUC of the IV dose of [14C]AZD9291 x IV dose/Oral dose x 100
16 secondary outcomes
AUC for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-24) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-120) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC(0-t) for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
Cmax for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
Tmax for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
t1/2,λz for AZD9291 and it's Metabolites AZ5104 and AZ7550
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
CL/F for AZD9291
Time frame: Samples taken at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 and 504 hours post-dose.
AUC for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-24) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-120) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
AUC(0-t) for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Cmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Tmax for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
t1/2,λz for [14C]AZD9291 and it's Metabolites [14C]AZ5104 and [14C]AZ7550
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
CL for [14C]AZD9291
Time frame: Samples taken pre-dose, during the infusion, immediately at the end of infusion and then at 5, 10, 20, 25 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 42, 66, 114, 162, 210, 330 and 498 hours after the end of the infusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29683562Vishwanathan K, So K, Thomas K, Bramley A, English S, Collier J. Absolute Bioavailability of Osimertinib in Healthy Adults. Clin Pharmacol Drug Dev. 2019 Feb;8(2):198-207. doi: 10.1002/cpdd.467. Epub 2018 Apr 23.
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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.
Joanne Collier, MBChB, FFPM, Dip Stats (OU) principal investigator
Quotient Clinical Ltd
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 AZD9291 and [14C]AZD9291 in people with Oncology, run by AstraZeneca at 1 site in United Kingdom.
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 7 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 13 Oct 2016. 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 Kingdom. 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 13 Oct 2016). 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?
Absolute Oral Bioavailability (time frame: Samples taken at pre-dose, 1, 2, 3, 4, 5:45, 5:52, 6, 6:05, 6:10, 6:20, 6:25, 6:30, 7, 8, 9, 10, 12, 14, 16, 18, 24, 30, 48, 72, 120, 168, 216, 336 and 504 hours relative to the oral dose.). 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 NCT02491944, which also lists 1 linked publication.
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 13 Oct 2016.