A Phase I, Open-label Study to Assess Bioavailability of a Single Oral Dose of AZD9291 vs an IV Dose of [14C]AZD9291

NCT02491944 | Completed Phase 1 Results

• 1 other identifier: D5160C00020
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Oncology

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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

  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

  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.

Study Arms (1)

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

Drug: AZD9291; Drug: [14C]AZD9291

Interventions

AZD9291 DRUG

Single oral dose of 80 mg AZD9291 tablet on Day 1 administered orally with 240 mL water following an overnight fast.

Bioavailability of AZD9291

[14C]AZD9291 DRUG

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.

Bioavailability of AZD9291

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Nottingham, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29683562 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

osimertinib

Results Point of Contact

• Title: Dr Karen So
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Joanne Collier, MBChB, FFPM, Dip Stats (OU)

  Quotient Clinical Ltd

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2015
• First Posted: July 8, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 13, 2016
• Results First Posted: October 13, 2016

Record last verified: 2016-08

Locations

GB (1)