A Study to Explore the Effect of Acid-reducing Agents

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Adults

Intervention / Treatment
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* Drug: Sitravatinib
* Drug: Pantoprazole
* Drug: Famotidine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2 period crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 Treatment A (sitravatinib only)<br>Period 1: A single oral dose of 100 mg sitravatinib on Day 1 | Drug: Sitravatinib<br>* 100 mg sitravatinib on Day 1<br>* Other names: MGCD516;|
| Experimental: Group 1 Treatment B (sitravatinib and pantoprazole)<br>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<br>* 100 mg sitravatinib on Day 1<br>* Other names: MGCD516;Drug: Pantoprazole<br>* 40 mg QD on Day 1 to Day 7 of Period 2 in Group 1<br>* Other names: Protonix;|
| Experimental: Group 2 Treatment C (sitravatinib only)<br>Period 1: A single oral dose of 100 mg sitravatinib on Day 1 | Drug: Sitravatinib<br>* 100 mg sitravatinib on Day 1<br>* Other names: MGCD516;|
| Experimental: Group 2 Treatment D (sitravatinib and famotidine)<br>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<br>* 100 mg sitravatinib on Day 1<br>* Other names: MGCD516;Drug: Famotidine<br>* 40 mg PO 2 hrs after sitravatinib in Period 2 of Group 2<br>* Other names: Pepcid;|

What is the study measuring?
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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 |