A Study to Explore the Effect of Acid-reducing Agents

A Phase 1 Study of the Effect of Acid-reducing Agents on the Pharmacokinetics of a Single Oral Dose of Sitravatinib in Healthy Adult Subjects

A Phase 1 Study of the Effect of Acid-reducing Agents on the Pharmacokinetics of a Single Oral Dose of Sitravatinib in Healthy Adult Subjects. The study is a single-center, open-label, 2-period, 2-treatment, fixed-sequence crossover, parallel-group study.

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: Sitravatinib; Drug: Pantoprazole; Drug: Famotidine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kg/m2, inclusive.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and/or check-in, as assessed by the investigator (or qualified designee).
• Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at screening and check-in. Females of childbearing potential must agree to use contraception.
• Male subjects must agree to use contraception.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Key Exclusion Criteria:

• Significant history of clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, any components of the IMP, or other substance (not including seasonal allergies), unless approved by the investigator.
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications. (Uncomplicated appendectomy and hernia repair are allowed. Cholecystectomy is not allowed.)
• History of Gilbert's syndrome or suspicion of Gilbert's syndrome based on elevated total and indirect bilirubin (may be confirmed by repeat).
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to study drug administration on Day 1 of Period 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Treatment A (sitravatinib only); Period 1: A single oral dose of 100 mg sitravatinib on Day 1	Drug: Sitravatinib; 100 mg sitravatinib on Day 1; Other Names: MGCD516
Experimental: Group 1 Treatment B (sitravatinib and pantoprazole); Period 2: Oral pantoprazole once daily for 7 days (Days 1 to 7) and a single oral dose of 100 mg sitravatinib on Day 7	Drug: Sitravatinib; 100 mg sitravatinib on Day 1; Other Names: MGCD516; Drug: Pantoprazole; 40 mg QD on Day 1 to Day 7 of Period 2 in Group 1; Other Names: Protonix
Experimental: Group 2 Treatment C (sitravatinib only); Period 1: A single oral dose of 100 mg sitravatinib on Day 1	Drug: Sitravatinib; 100 mg sitravatinib on Day 1; Other Names: MGCD516
Experimental: Group 2 Treatment D (sitravatinib and famotidine); Period 2: A single oral dose of 100 mg sitravatinib followed by a single oral dose of famotidine 40 mg approximately 2 hours after sitravatinib dose on Day 1	Drug: Sitravatinib; 100 mg sitravatinib on Day 1; Other Names: MGCD516; Drug: Famotidine; 40 mg PO 2 hrs after sitravatinib in Period 2 of Group 2; Other Names: Pepcid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax (sitravatinib)	Maximum observed plasma concentration	Up to Day 7 after dosing
Pharmacokinetics - AUC∞ (sitravatinib)	Area under the plasma concentration-time curve from time zero extrapolated to infinity	Up to 72 hours after dosing
Pharmacokinetics - AUClast (sitravatinib)	Area under the curve from time zero to the last measured time point	Up to 72 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Incidence and severity of AEs	Up to 9 weeks from screening

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): August 12, 2021
• Study Completion (Actual): July 12, 2022

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine; Pantoprazole
• Other Study ID Numbers: 516-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No