A Study to Assess the Effects of Fluvoxamine on Savolitinib Exposure in Healthy Male Subjects

NCT ID: NCT05888207

Last Updated: 2023-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-02
• Study Completion Date: 2023-08-17

Brief Summary

This study will assess the effects of strong CYP1A2 (Cytochrome P450 1A2) inhibitor (fluvoxamine) on savolitinib exposure in healthy male subjects, performed at a single clinical unit.

Detailed Description

This study will be a Phase I, open-label, fixed-sequence, 2-treatment period study.

The study will consist of 2 periods. During period 1 of the study, each subject will receive a single oral dose of savolitinib following an overnight fast. A low-fat breakfast will be provided prior to dosing. There will be a minimum washout period of 10 days (14 days between two successive savolitinib doses) between period 1 and period 2.

During period 2 of the study, subject will take oral doses of fluvoxamine alone from Days 1 to 4. There would be no dietary restrictions for fluvoxamine dosing. On Day 5, subjects will take a single oral dose of savolitinib and oral dose of fluvoxamine. On Day 6, subject will receive an oral dose of fluvoxamine alone. Each subject would be involved in the study for 9 weeks (including screening window).

Conditions

Healthy Male Subjects

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Savolitinib/Savolitinib+Fluvoxamine

In period 1, subjects will receive a single oral dose of savolitinib on Day 1 after overnight fasting. Following minimum 10 days of washout after the last dose of savolitinib, in period 2 subjects will take oral doses of fluvoxamine alone, twice daily from Days 1 to 4. On Day 5 subject will receive a single oral dose of savolitinib and a twice daily oral dose of fluvoxamine. On Day 6, subjects will receive a twice daily oral dose of fluvoxamine alone.

Group Type: EXPERIMENTAL

Savolitinib

Intervention Type: DRUG

Savolitinib will be administered as a single oral dose on Day 1 of Period 1 and on Day 5 of Period 2.

Fluvoxamine

Intervention Type: DRUG

Only fluvoxamine will be administered as a twice daily oral dose from Days 1 to 4 of Period 2. On Day 5 of Period 2, subject will receive a twice daily oral dose of fluvoxamine along with savolitinib. On Day 6 of Period 2, subject will receive a twice daily oral dose of fluvoxamine alone.

Interventions

Savolitinib

Savolitinib will be administered as a single oral dose on Day 1 of Period 1 and on Day 5 of Period 2.

Intervention Type: DRUG

Fluvoxamine

Only fluvoxamine will be administered as a twice daily oral dose from Days 1 to 4 of Period 2. On Day 5 of Period 2, subject will receive a twice daily oral dose of fluvoxamine along with savolitinib. On Day 6 of Period 2, subject will receive a twice daily oral dose of fluvoxamine alone.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy subjects with suitable veins for cannulation or repeated venipuncture.
• Male subjects must use barrier contraception.
• Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Regular bowel movements.

Exclusion Criteria

• History of any clinically significant disease or disorder, which in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, vital signs, 12 lead ECG and physical examination.
• QTcF > 450 ms or QT > 500 ms or other ECG abnormality making interpretation more difficult, as judged by the investigator, or a history of additional risk factors for Torsades de Points, which in the opinion of the investigator may put the subject at risk.
• Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B, hepatitis C antibody, or HIV antibody.
• History of latent or chronic infections.
• Known or suspected drug or alcohol abuse or positive drugs of abuse test. History of excessive alcohol assumption or chronic alcohol induced disease. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 1 month (30 days) of Visit 2 (Day -1 of Period 1) or 5 half lives whichever longer in this study or participation in a method development study (no drug) 1 month prior to Visit 2. The period of exclusion begins 1 month after the final dose or 5 half-lives after the final dose or 1 month after the last visit, whichever is the longest.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
• Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 6 months prior to screening.
• Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies (which include but are not limited to: kava, ephedra [ma hung], ginko biloba, dehydroepiandrosterone, yohimbe, saw palmetto and ginseng), megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer (> 5 half-lives) if the medication has a long half-life.
• Subject has clinical signs and symptoms consistent with COVID-19, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission unless confirmed by a negative SARS CoV-2 PCR test.
• History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
• Excessive intake of caffeine-containing drinks or food.
• Planned in-patient surgery, dental procedure, or hospitalization during the study.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug.
• Received a seasonal flu vaccine (including H1N1, H1N5) 28 days prior to first dose of study drug.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Brooklyn, Maryland, United States

Countries

United States

Other Identifiers

D5084C00015

Identifier Type: -

Identifier Source: org_study_id