NCT04121910

A Study to Evaluate the Amount of Drug That Becomes Available in the Blood Circulation When Savolitinib is Administered Alone and in Combination With Itraconazole

An Open-label, 3-period Fixed-sequence Study in Healthy Subjects to Assess the Pharmacokinetics (PK) of Savolitinib When Administered Alone and in Combination With Itraconazole

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: Male
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study will be conducted to quantify the magnitude of the effect of itraconazole co-administration on the PK of savolitinib. The exposure to savolitinib is predicted to increase when co-administered with the potent cytochrome P (CYP) 3A4 inhibitor itraconazole since CYP3A4 (via CYP450) is involved in the metabolism and elimination of savolitinib.

Detailed description

This study will be an open-label, 3-period, fixed-sequence study in non-Japanese healthy male subjects conducted at a single study centre. The study will comprise: 1. A screening period of maximum 28 days; 2. Three treatment periods: 1. Treatment Period 1 consists of 15 days with admission on Study Day -1, followed by a single dose administration of savolitinib on Study Day 1 followed by a washout period of at least 14 days. Subjects will be discharged from the study centre on Day 3, after the last PK sample is collected. 2. Treatment Period 2 consists of 4 days with admission on Study Day 14, followed by itraconazole administration for 3 days (200 mg BID on Study Day 15, 200 mg QD on Study Days 16 and 17). 3. Treatment Period 3 consists of 3 days, starting immediately after the end of Treatment Period 2 comprising of single dose administration of savolitinib (200 mg) on Study Day 18 and itraconazole administration (200 mg QD) on Study Days 18 and 19. The subjects will be discharged from the study centre on Study Day 20 after the last PK sample. 3. The Follow-up Visit will occur at least 14 days after the last dose of savolitinib PK sample in Treatment Period 3. 4. Subjects will be admitted to the study centre on 2 different occasions: Study Day-1 (Study Day -1) to Study Day 3 of Treatment Period 1 and Day -1 (Study Day 14) of Treatment Period 2 to Day 3 (Study Day 20) of Treatment Period 3. The study drugs will be administered as follows: 1. Treatment Period 1: Single administration of savolitinib (200 mg) will occur on Study Day 1 after a high-fat, high-calorie breakfast followed by PK sampling for 48 hours. 2. Treatment Period 2: Itraconazole administered BID (200 mg BID) on Study Day 15, and (200 mg QD) on Study Days 16 and 17, 1 hour before breakfast (and before dinner, when applicable). 3. Treatment Period 3: A single combination of itraconazole (200 mg) 1 hour before breakfast + savolitinib (200 mg) after a high-fat, high-calorie breakfast on Study Day 18, and a single dose of itraconazole (200 mg) on Study Day 19, 1 hour before breakfast. Each subject will be involved in the study for up to 60 days.

Conditions

• Solid Tumour

Interventions

Type	Name	Description
DRUG	Savolitinib	On Study Day 1 and Study Day 18, savolitinib will be administered as single dose after a high-fat, high-calorie breakfast
DRUG	Itraconazole	Twice daily on first day of dosing (Study Day 15) followed by once daily for 4 days (Study Day 16 - Study Day 19) administered 1 hour before any breakfast (and 1 hour before dinner on Study Day 15)

Timeline

• Start date: 2019-11-07
• Primary completion: 2020-01-12
• Completion: 2020-01-12
• First posted: 2019-10-10
• Last updated: 2020-01-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study