To Assess the Effect of Rifampicin on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers

Solid Tumours Clinical Trial

Official title:

A Phase I Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inducer Rifampicin on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02046850
• Other study ID #: D1532C00085
• Status: Completed
• Phase: Phase 1
• First received: January 24, 2014
• Last updated: April 28, 2014
• Start date: February 2014
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Study to assess the effect of Rifampicin on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Description:

A Open-label, Single-center Study to Assess the Effect of the CYP3A4 inducer Rifampicin on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Volunteers

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria: 1. Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive). 2. Must not have smoked or used nicotine products within the previous 3 months. 3. Have a calculated creatinine clearance (CrCL) greater than 50 mL/min using the Cockcroft-Gault formula.

Exclusion Criteria: 1. Subjects of Japanese or non-Japanese Asian ethnicity. 2. Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (eg, China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.

3. Current or past history of central serous retinopathy or retinal vein thrombosis,intra-ocular pressure greater than 21 mmHg or uncontrolled glaucoma. 4. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at baseline in the opinion of the investigator.

5. History of presence of any clinically significant disease or disorder in the opinion of the investigator.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Solid Tumours

Intervention

Drug:
• selumetinib
Volunteers will receive a single oral dose of 75 mg selumetinib on day 1 (Treatment A).
• rifampicin
Volunteers will receive single, daily, oral doses of 600 mg rifampicin on Days 4 to 11 (Treatment B).
• selumetinib
On day 12 volunteers will receive a single oral dose of 75 mg selumetinib (Treatment C).
• rifampicin
On day 12 volunteers will receive a single oral dose of 600 mg rifampicin. Once daily rifampicin administrations will continue through to Day 14 (Treatment C).

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 examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments, and 12 lead electrocardiograms)	Assessments performed during each of the 3 treatments	Baseline (Day-1) up to Day 25	Yes
Primary	Pharmacokinetics of selumetinib by assessment of area under the plasma concentration-time curve from time zero to infinity (AUC)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of area under the plasma concentration-time from time zero to the time of the last quantifiable concentration (AUC(0-t)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of area under the plasma concentration-time curve from time zero to 12 hours post-dose AUC(0-12)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of maximum plasma concentration (Cmax)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of time to Cmax (tmax)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, by assessment of apparent systemic plasma clearance (CL/F)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, by assessment of apparent volume at distribution equilibrium, mean residence time (MRT)*CL/F (Vss/F)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, by assessment of apparent volume at distribution (Vz/F)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of terminal half-life (t1/2)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of terminal rate constant (?z)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of AUC metabolite to parent ratio, n-desmethyl selumetinib (MRAUC)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of Cmax metabolite to parent ratio, n-desmethyl selumetinib (MRCmax)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No
Secondary	Pharmacokinetics of selumetinib by assessment of mean residence time (MRT)	Samples taken during each of the 3 treatments	Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose	No