Solid TumoursPhase 1NCT02093728
To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers
A Phase 1 study testing selumetinib, itraconazole and fluconazole in people with Solid Tumours, run by AstraZeneca at 1 site in United States.
Trial summary
Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Solid Tumours
- What is being tested?
- selumetinib, itraconazole and fluconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Jun 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
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. 2. Female subjects of non-childbearing potential. 3. Have a calculated creatinine clearance (CrCL) >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 (ie, 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 >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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years
Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers
Read the detailed description
A Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers
- Conditions
- Solid Tumours
- Being tested
- selumetinib, itraconazole, fluconazole
- Keywords
- Phase I, healthy, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selumetinibDrug
Also called (AZD6244; ARRY-142866) ( Hyd-Sulfate)
Volunteers will recieve single oral dose of 25mg selumetinib in sequence 1, treatment A
itraconazoleDrug
Volunteers will receive oral doses of itraconazole 200 mg twice daily on Day 1 to Day 7 in sequence 1 treatment B:
itraconazoleDrug
Volunteers will recieve a single morning dose of 200mg itraconazole on Day 8 and twice daily doses of 200mg itraconazole on Day 8 to Day 11; sequence 1 treatment C.
selumetinibDrug
Also called (AZD6244; ARRY-142866) ( Hyd-Sulfate)
Volunteers willl recieve a single oral dose of 25 mg selumetinib (4 hours fasted state) on Day 8; sequence 1 treatment C.
selumetinibDrug
Also called (AZD6244; ARRY-142866) ( Hyd-Sulfate)
Volunteers will recieve single oral dose of 25mg selumetinib in sequence 2, treatment A.
fluconazoleDrug
Volunteers will recieve a single dose of 400 mg fluconazole on Day 1 and daily doses of 200 mg fluconazole on Day 2 to Day 7; sequence 2 treatment D.
fluconazoleDrug
Volunteers will receive a morning dose of 200mg fluconazole on Day 8 and daily doses of 200mg fluconazole on Day 8 to Day 11; sequence 2 treatment E
selumetinibDrug
Volunteers will receive a single dose of 25mg selumetinib (4 hours fasted state) on Day 8; sequence 2 treatment E
| Study group | Role | What they receive |
|---|---|---|
| selumetinib; itraconazole; selumetinib + itraconazole | Experimental | Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule Receives: Drug: selumetinib; Drug: itraconazole |
| selumetinib; fluconazole; selumetinib + fluconazole | Experimental | Volunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg. Receives: Drug: selumetinib; Drug: fluconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Secondary outcomes (12)
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement 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 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement 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 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (λz)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of mean residence time (MRT)
Samples taken during each of the 6 treatments
Measured: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2014 (estimated)
- Study startApr 2014
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumoursStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David R Mathews, MD, Principal investigator, Quintiles 6700 W 115th Street, Kansas, US
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02093728
- Sponsor's protocol ID
- D1532C00083
- Status last verified
- Jun 2015
- First submitted
- 20 Mar 2014
- Last updated
- 30 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years
- ClinicalTrials.gov ID
- NCT02093728
- Acronym / sponsor ID
- D1532C00083
- Conditions
- Solid Tumours
- Keywords
- Phase I, healthy, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 21 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers
Detailed description
A Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| selumetinib; itraconazole; selumetinib + itraconazole | Experimental | Drug: selumetinib, Drug: itraconazoleVolunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule |
| selumetinib; fluconazole; selumetinib + fluconazole | Experimental | Drug: selumetinib, Drug: fluconazoleVolunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
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 |
|---|---|---|
| selumetinibAlso: (AZD6244; ARRY-142866) ( Hyd-Sulfate)Volunteers will recieve single oral dose of 25mg selumetinib in sequence 1, treatment A | Drug | selumetinib; itraconazole; selumetinib + itraconazole |
| itraconazoleVolunteers will receive oral doses of itraconazole 200 mg twice daily on Day 1 to Day 7 in sequence 1 treatment B: | Drug | selumetinib; itraconazole; selumetinib + itraconazole |
| itraconazoleVolunteers will recieve a single morning dose of 200mg itraconazole on Day 8 and twice daily doses of 200mg itraconazole on Day 8 to Day 11; sequence 1 treatment C. | Drug | selumetinib; itraconazole; selumetinib + itraconazole |
| selumetinibAlso: (AZD6244; ARRY-142866) ( Hyd-Sulfate)Volunteers willl recieve a single oral dose of 25 mg selumetinib (4 hours fasted state) on Day 8; sequence 1 treatment C. | Drug | selumetinib; itraconazole; selumetinib + itraconazole |
| selumetinibAlso: (AZD6244; ARRY-142866) ( Hyd-Sulfate)Volunteers will recieve single oral dose of 25mg selumetinib in sequence 2, treatment A. | Drug | selumetinib; fluconazole; selumetinib + fluconazole |
| fluconazoleVolunteers will recieve a single dose of 400 mg fluconazole on Day 1 and daily doses of 200 mg fluconazole on Day 2 to Day 7; sequence 2 treatment D. | Drug | selumetinib; fluconazole; selumetinib + fluconazole |
| fluconazoleVolunteers will receive a morning dose of 200mg fluconazole on Day 8 and daily doses of 200mg fluconazole on Day 8 to Day 11; sequence 2 treatment E | Drug | selumetinib; fluconazole; selumetinib + fluconazole |
| selumetinibVolunteers will receive a single dose of 25mg selumetinib (4 hours fasted state) on Day 8; sequence 2 treatment E | Drug | selumetinib; fluconazole; selumetinib + fluconazole |
Primary outcome
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Samples taken during each of the 6 treatments
12 secondary outcomes
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time from time zero to the time of the last quantifiable concentration (AUC(0-t)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time curve from time zero to 12 hours post-dose AUC(0-12)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (λz)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Pharmacokinetics of selumetinib by assesement of mean residence time (MRT)
Time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2015.
- CSR\_Synopsis\_D1532C00083Link provided by the sponsor.
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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.
David R Mathews, MD principal investigator
Quintiles 6700 W 115th Street, Kansas, US
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 selumetinib, itraconazole and fluconazole in people with Solid Tumours, 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?
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 30 Jun 2015. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) (time frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jun 2015.