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Also known as CYP1A2 (caffeine)
CYP1A2 · 1 trial · 1 indication
To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)
To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)
To assess the effect of AZD1775 on the PK of probe substrates for CYP1A2 (caffeine), CYP2C19 (omeprazole), and CYP3A (midazolam)
To assess the effect on QT interval corrected for heart rate (QTc) following multiple oral doses of AZD1775
| Arm | Type | Description |
|---|---|---|
| Wee-1 kinase inhibitor AZD1775 | EXPERIMENTAL | To 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 |
| Name | Type | Description |
|---|---|---|
| CYP1A2 (caffeine) | DRUG | In 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) | DRUG | In 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) | DRUG | In 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) | DRUG | Patients 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 AZD1775 | DRUG | Multiple doses of 225 mg AZD1775, (3 x 75 mg, printed capsules) administered orally. The drug class of AZD1775 is Wee-1 kinase inhibitor. |
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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
CYP1A2 is a cytochrome P450 enzyme that metabolizes certain drugs and other substances, including caffeine. In this program it is studied as a pharmacokinetic marker in oncology, evaluated in a Phase 1 trial of AZD1775 in patients with advanced solid tumours.
CYP1A2 is being studied by AstraZeneca PLC, which trades under the ticker AZN. The company sponsored the Phase 1 trial NCT03333824, which examined the effects of AZD1775 on CYP1A2 and other drug-metabolizing enzymes in patients with advanced cancer.
CYP1A2 is in Phase 1 development. It has been evaluated in a single Phase 1 trial, NCT03333824, which is now completed. The study enrolled 33 patients with solid tumours in the United States and was an uncontrolled, non-randomized design.
CYP1A2 has been studied in one clinical trial, NCT03333824, titled Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer. The Phase 1 trial enrolled 33 patients with solid tumours, was conducted in the United States, and is completed.
Yes, CYP1A2 is also referred to as CYP1A2 (caffeine). The parenthetical reflects that caffeine is a known substrate used to probe the activity of this cytochrome P450 enzyme. Both names refer to the same enzyme evaluated in the AstraZeneca Phase 1 oncology trial.
CYP1A2 is not a therapeutic agent; it is a drug-metabolizing enzyme assessed as a pharmacokinetic marker. In solid tumours research, it was measured in a Phase 1 trial of AZD1775 to evaluate drug interaction effects on CYP1A2 and related enzymes in patients with advanced cancer.