A Study to Assess the Effects of Savolitinib on the Pharmacokinetics of Digoxin, Rosuvastatin, Metformin, and Furosemide in Healthy Male Subjects
Condition: Healthy Male Subjects
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will assess the effects of savolitinib on the pharmacokinetics (PK) of substrates
      of human transporters digoxin (P-gp), rosuvastatin (OATP1B1/3), metformin (OCT2, MATE1/2K),
      and furosemide (OAT1/3) in healthy male subjects, performed at a single clinical unit.
    

Detailed description: 
      This study will be performed at a single clinical unit.

      Subjects will be admitted to the clinical unit on Day -1 of Period 1 and Period 2. Subjects
      will have a washout period of 14 days between Period 1 and Period 2.

      Period 1: Subjects will recieve a single dose of a drug cocktail of 4 medications (digoxin
      Dose B, furosemide Dose C, metformin hydrochloride Dose D, and rosuvastatin Dose E).

      Period 2: Participants will receive savolitinib (Dose A) in combination with the drug
      cocktail of 4 medications as received in Period 1.

      The study will consist of 4 visits:

      Visit 1 (Enrollment): Following full written informed consent, subjects will be screened for
      eligibility.

      Visit 2 (Period 1: Treatment and Sample Collection Period): Each subject will be admitted to
      the clinical unit on Day -1 of Period 1, single dose of drug cocktail is administered on Day
      1, and remain in clinical unit until Day 5 assessments. A washout period of 14 days is
      followed.

      Visit 3 (Period 2: Treatment and Sample Collection Period): Each subject will be admitted to
      the clinical unit on Day -1 of Period 2, single dose of savolitinib and drug cocktail is
      administered, and remain in clinical unit until Day 5 assessments.

      Visit 4 (Follow-up): Subjects will attend the clinical unit for a final Follow-up Visit 5 to
      7 days post Day 5 in Period 2.

      Each subject will be involved in the study for 9 weeks including screening to final follow
      up.
    

Intervention name(s): Savolitinib; Digoxin; Metformin Hydrochloride; Rosuvastatin; Furosemide
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): The subjects will receive single dose of oral film-coated tablet of Savolitinib A dose on Day 1 of Period 2 within 25 minutes [+ 5 minutes] from the start of meal.; The subjects will receive single dose of oral uncoated tablet of Digoxin Dose B on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.; The subjects will receive single dose of oral film-coated tablet of Metformin Hydrochloride Dose D on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.; The subjects will receive single dose of oral film-coated tablet of Rosuvastatin Dose E on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.; The subjects will receive single dose of oral solution of Furosemide Dose C on Day 1 of Period 1 and Period 2 within 25 minutes [+ 5 minutes] from the start of meal.
Intervention MeSH terms: Metformin; Digoxin; Furosemide; Rosuvastatin Calcium
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Drug-Drug Interaction; Substrate of human drug transporters; Fixed-sequence; Drug cocktail