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

NCT05888207 | Completed Phase 1 FDA Drug

• 1 other identifier: D5084C00015
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Male Subjects

Keywords

Fixed-sequence; CYP1A2 inhibitor; Drug-drug interaction

Outcome Measures

Primary Outcomes (2)

• Maximum observed plasma (peak) drug concentration (Cmax) for savolitinib

  To evaluate the effects of fluvoxamine on savolitinib Cmax in healthy male subjects after administration of a single oral dose.

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

• Area under plasma concentration time curve from zero to infinity (AUCinf) for savolitinib

  To evaluate the effects of fluvoxamine on savolitinib AUCinf in healthy male subjects after administration of a single oral dose.

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

Secondary Outcomes (14)

• Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for savolitinib

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

• AUClast for metabolites M2 and M3

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

• Cmax for metabolites M2 and M3

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

• AUCinf for metabolites M2 and M3

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

• Ratio of metabolite Cmax to parent Cmax (MRCmax)

  Period 1: Day 1 to Day 3 and Period 2: Day 5 to Day 7

Study Arms (1)

Savolitinib/Savolitinib+Fluvoxamine

EXPERIMENTAL

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.

Drug: Savolitinib; Drug: Fluvoxamine

Interventions

Savolitinib DRUG

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

Savolitinib/Savolitinib+Fluvoxamine

Fluvoxamine 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.

Savolitinib/Savolitinib+Fluvoxamine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; Fluvoxamine

Intervention Hierarchy (Ancestors)

Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 5, 2023
• Study Start: June 2, 2023
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (1)