NCT03333824

Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer

A Phase I Open-label Study to Evaluate the Effect of Multiple Doses of AZD1775 on the Pharmacokinetics of Substrates for CYP3A, CYP2C19, CYP1A2 and to Provide Data on the Effect of AZD1775 on QT Interval in Patients With Advanced Solid Tumours

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether AZD1775 has any effect on the pharmacokinetics (PK) of three compounds (caffeine, omeprazole, and midazolam) that are probes for common drug-metabolizing enzymes (caffeine-CYP1A2, omeprazole-CYP2C19, midazolam-CYP3A). The study also seeks to determine the effect of AZD1775 on the QTc interval, which is a common measure of cardiac (heart) function.

Detailed description

This is a Phase I, 2-part study (Part A and Part B) in patients with advanced solid tumours. Part A: Part A of this study is an open-label, non-randomised, 2-period design. The treatment starts with the administration of a cocktail of 3 medications: caffeine, omeprazole and midazolam (Day -8), followed by pharmacokinetic (PK) sampling for 24 hours (Period 1) and a washout period of at least 7, but no more than 14 days. In Period 2, AZD1775 will be administered twice daily (bid) until steady state for 2.5 days (total of 5 doses) and the final dose will be administered in combination with the cocktail in the morning of Day 3. Part B: Part B is an open-label, non-randomised study in the same patients who participated in Part A. On Day -1, baseline dECG assessments will be performed at clock times matched to planned/scheduled dECG assessment times on Days 1 and 3. Starting on Day 1, each patient will receive AZD1775 (225 mg) bid for 2.5 days and will undergo dECG and PK assessments pre-dose and for 12 hours post AZD1775 dose. On Day 3, patients will receive their final AZD1775 dose and undergo dECG and PK assessments pre-dose and for 12 hours post-dose. On completion of Part B (ie, collection of the 24-hour PK sample/dECG and safety assessments on Day 4) patients will enter a 4-day washout period relative to the last dose of AZD1775. Within 3 days after the washout period, patients will be required to attend an end of treatment (EoT) visit. Patients will be evaluated for their eligibility and interest to enrol into the open-label continued access (CA) study (D6014C00007).

Conditions

• Solid Tumours

Interventions

Type	Name	Description
DRUG	CYP1A2 (caffeine)	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.
DRUG	CYP2C19 (omeprazole)	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.
DRUG	CYP3A (midazolam)	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.
DRUG	Kytril (granisetron)	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.
DRUG	Wee-1 kinase inhibitor AZD1775	Multiple doses of 225 mg AZD1775, (3 x 75 mg, printed capsules) administered orally. The drug class of AZD1775 is Wee-1 kinase inhibitor.

Timeline

• Start date: 2017-12-01
• Primary completion: 2019-01-22
• Completion: 2019-01-22
• First posted: 2017-11-07
• Last updated: 2019-03-25

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study