To Determine the Relative Bioavailability of Different Formulations of AZD9291 and the Effect of Food.

Healthy Volunteers Clinical Trial

Official title:

A Phase I, Open-label, Single-center, Sequential Design Study in Healthy Volunteers to Determine the Relative Bioavailability of Different Oral Formulations of AZD9291 and the Effect of Food

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951599
• Other study ID #: D5160C00005
• Status: Completed
• Phase: Phase 1
• First received: September 24, 2013
• Last updated: March 30, 2017
• Start date: October 9, 2013
• Est. completion date: June 4, 2014

Study information

• Verified date: March 2017
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the relative bioavailability of different oral formulations of AZD9291 and the effect of food in healthy volunteers.

Description:

A Phase I, Open-label, Single-center, Sequential Design Study in Healthy Volunteers to Determine the Relative Bioavailability of Different Oral Formulations of AZD9291 and the Effect of Food

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 4, 2014
• Est. primary completion date: June 4, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1, Body mass index between 19 and 30 kg/m2 and weight at least 50 kg and no more than 100 kg. 2, Volunteers must be willing to use a condom, unless their partners are postmenopausal, surgically sterile, or using an effective hormonal method of contraception or intrauterine coil. 3. In addition, volunteers must agree to continue to take similar contraceptive precautions until 4 months after the last dose of AZD9291.

Exclusion Criteria:

1. Any clinically relevant abnormalities in physical examination, vital signs, hematology, clinical chemistry, urinalysis or ECG at baseline in the opinion of the Investigator.

2. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to dosing.

3. History of severe allergy/hypersensitivity or or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to AZD9291, its excipients, or drugs with a similar chemical structure or class.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule on day 1, in Part A, Period 1, in the fasted state. (Treatment A).
• AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a solution on day 1, in Part A, Period 2, in the fasted state. (Treatment B).
• AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a tablet on day 1, in Part A, Period 3, in the fasted state. (Treatment C).
• AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule or tablet on day 1, in Part B, Period 1, in the fasted state.
• AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule or tablet on day 1, in Part B, Period 2, in the fed state.

Locations

Country	Name	City	State
United States	Research Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety variables (adverse events, physical exam, vital signs, ECG's, clinical laboratory safety tests, opthalmological examination)	Assessments performed during each of the 5 treatments.	Baseline (Day-1) to Day 28
Primary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of maximum plasma concentration (Cmax)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites by assessment of the area under the plasma concentration-time curve from zero to infinity (AUC)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of time to Cmax (tmax)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal rate constant (?z)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal half life (t1/2,?z)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of lag time before observation of quantifiable analyte concentrations in plasma (tlag)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to time of last measurable concentration [AUC(0-t)]	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to 72 hours [AUC(0-72)]	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 only, by assessment of apparent plasma clearance (CL/F).	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 only, apparent volume of distribution (Vz/F)	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose
Secondary	Pharmacokinetics of AZD9291 parent to metabolite ratio (calculated for both Cmax and AUC).	Curve taken during each of the 5 treatments	Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose

External Links

•   D5160C00005_CSR_Synopsis
•   D5160C00005revised_csp_2_signed_31March 16_REDACTED