A Study in Healthy Male Subjects to Understand How Savolitinib Behaves Inside the Body (Pharmacokinetics) When Administered Alone and in Combination With Famotidine

NCT04179071 | Completed Phase 1 FDA Drug

• 1 other identifier: D5084C00005
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open-label, randomised, 2 part (Part A and Part B), 2 treatment (savolitinib alone or in combination with famotidine), crossover study in healthy, non Japanese, male subjects, performed at a single study centre.

Conditions

Solid Tumours

Keywords

Famotidine; Drug-drug interaction study; Small molecule kinase inhibitor

Outcome Measures

Primary Outcomes (2)

• Maximum observed plasma concentration (Cmax) ratio

  Cmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

• Area under plasma concentration-time curve from zero to infinity (AUC) ratio

  AUC ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

Secondary Outcomes (12)

• Number of subjects with having adverse events and/or abnormal findings in vital signs and/or laboratory evaluation and/or physical examination

  From 28-day screening period to follow-up period i.e. 60 days

• AUC geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

• Area under the plasma concentration curve from time zero to time of last quantifiable concentration AUC(0-t)

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

• Cmax geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

• Cmax metabolite-to-parent ratios (MRCmax)

  At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18

Study Arms (2)

Savolitinib

EXPERIMENTAL

Subjects will receive single dose of 600mg savolitinib after a high-fat, high-calorie meal.

Drug: Savolitinib

Savolitinib + Famotidine

EXPERIMENTAL

Subjects will receive savolitinib 600mg single dose after high-fat, high-calorie meal and after 1.5 hours (Part A) or 5.5 hours (Part B) of famotidine 40mg dose. Famotidine will be administered after an overnight fast of at least 8 hours with approximately 240 mL of water.

Drug: Savolitinib; Drug: Famotidine

Interventions

Savolitinib DRUG

Subject will receive savolitinib tablet 600mg orally after a high-fat, high-calorie meal.

Savolitinib; Savolitinib + Famotidine

Famotidine DRUG

Subjects will receive famotidine tablet 40mg orally after an overnight (minimum 8hours) of fasting.

Savolitinib + Famotidine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated written informed consent prior to any study specific procedures.
• Healthy, non-Japanese male subjects with suitable veins for cannulation or repeated venipuncture: male subjects aged 18 to 65 years (inclusive).
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive; and weigh at least 50 kg and no more than 100 kg inclusive.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) less than or equal to the upper limit of normal for the institution.
• Have a calculated creatinine clearance greater than 80 mL/min using the Cockcroft-Gault formula at screening.
• Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

You may not qualify if:

• Subject that has at least 1 parent or grandparent (maternal or paternal) of Japanese ethnicity.
• Subjects who screen positive for Helicobacter pylori bacteria.
• History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of either study drug (savolitinib or famotidine).
• Planned in-patient surgery, dental procedure, or hospitalisation during the study.
• Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the PI.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Abnormal vital signs, after 5 minutes supine rest, defined as any of the following:
• Systolic BP \<90 mmHg or ≥140 mmHg
• Diastolic BP \<50 mmHg or ≥90 mmHg
• Heart rate \<45 or \>85 beats per minute.
• Any clinically important abnormalities in rhythm, conduction or morphology of the 12 lead resting electrocardiogram (ECG) that may interfere with the interpretation of QTc interval changes. These include healthy subjects with any of the following:
• Abnormal ST-T-wave morphology, particularly in the protocol-defined primary lead (V2) or left ventricular hypertrophy.
• PR interval shortening \<120 ms (PR \>110 ms but \<120 ms is acceptable if there is no evidence of ventricular pre-excitation).

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Baltimore, 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; Famotidine

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dr. Ronald Goldwater, MD

  Parexel Early Phase Clinical Unit Baltimore (Study Centre)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 26, 2019
• Study Start: December 13, 2019
• Primary Completion: March 11, 2020
• Study Completion: March 11, 2020
• Last Updated: July 7, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)