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CYP1A2

Phase 1

Solid Tumours | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Mar 25, 2019

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment33

FDA Designations

No designations recorded

Clinical trial landscape

CYP1A2 · 1 trial · 1 indication

Phase 1 1
NCT03333824Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced CancerSolid Tumours
COMPLETED33 Analytics
PHASE1COMPLETED
Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer
Solid TumoursUnlock trial analytics

Study Endpoints

Primary Endpoints

Part A: Area under the plasma concentration-time curve from zero to infinity for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8 and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post cocktail dose

To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)

Part A: Area under the plasma concentration-time curve from time zero to the time "t" of the last quantifiable concentration for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8 and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post cocktail dose

To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)

Part A: maximum plasma drug concentration for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8 and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post cocktail dose

To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)

Part B: dECG intervals (QTcF) for absolute values and time-matched change from baseline
dECGs are measured on Day -1, Day 1 and Day 3 of Part B at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post AZD1775 dose

To assess the effect on QT interval corrected for heart rate (QTc) following multiple oral doses of AZD1775

Secondary Endpoints

Time to reach maximum plasma concentration for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8, and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post dose
Terminal half-life for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8, and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post dose
Elimination rate constant for cocktail parent compounds (midazolam, omeprazole and caffeine)
Blood samples are collected on Day -8, and Day 3 of Part A at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post dose
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Wee-1 kinase inhibitor AZD1775EXPERIMENTALTo evaluate the effect of multiple doses of AZD1775 on the PK of substrates for CYP3A (midazolam), CYP2C19 (omeprazole), CYP1A2 (caffeine) and to evaluate the effect of multiple doses of AZD1775 on QT interval

Interventions

NameTypeDescription
CYP1A2 (caffeine)DRUGIn Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.
CYP2C19 (omeprazole)DRUGIn Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.
CYP3A (midazolam)DRUGIn Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.
Kytril (granisetron)DRUGPatients should be administered Kytril (granisetron) 1 mg orally, under fasted conditions (-2 to 2 hours away from meals), 30 minutes prior to administration of the AZD1775 capsules with a small amount of water.
Wee-1 kinase inhibitor AZD1775DRUGMultiple doses of 225 mg AZD1775, (3 x 75 mg, printed capsules) administered orally. The drug class of AZD1775 is Wee-1 kinase inhibitor.
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Eligibility Criteria

Age Range18 Years to 99 Years
SexALL
Healthy VolunteersNo
Study Sites7

Inclusion Criteria: * Has read and understands the informed consent form (ICF) and has given written informed consent prior to any study procedures. * Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exi...

Countries:United States
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Competitive Landscape -Other Solid Tumors 9 trials (matched to "Solid Tumours")

Frequently asked questions about CYP1A2

What is CYP1A2?

CYP1A2 is an investigational small molecule being studied in oncology. It is being developed by AstraZeneca PLC for the treatment of solid tumours. The drug is currently in Phase 1 clinical development, with one completed trial involving 33 patients.

What is CYP1A2 used for in solid tumours?

CYP1A2 is being studied for use in solid tumours. It is an investigational small molecule in Phase 1 clinical development. The completed trial evaluated its effects on drug metabolism and QT interval in patients with advanced cancer.

Who makes CYP1A2?

CYP1A2 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker AZN. The drug is an investigational small molecule in Phase 1 clinical development for the treatment of solid tumours.

What phase is CYP1A2 in?

CYP1A2 is in Phase 1 clinical development. It is an investigational small molecule being studied for solid tumours. The drug has one completed Phase 1 trial, and it is not yet approved by regulatory authorities.

What clinical trials is CYP1A2 in?

CYP1A2 has one completed clinical trial, NCT03333824, titled 'Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer'. This Phase 1 study enrolled 33 patients with solid tumours in the United States.

Is CYP1A2 the same as AZD1775?

CYP1A2 is not the same as AZD1775. The clinical trial NCT03333824 evaluated the effects of AZD1775 on CYP1A2, which is a drug-metabolizing enzyme, not the investigational drug itself. CYP1A2 is the name of the enzyme being studied as a substrate in the trial.