Study in Healthy Volunteers to Assess Effect of Omeprazole and Ranitidine on the Pharmacokinetics of Vandetanib

Study Overview
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Brief Summary
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Study in healthy volunteers to assess effect of omeprazole and ranitidine on the pharmacokinetics of vandetanib

Detailed Description
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A Phase I, Randomized, Open-label, Single-center Study to Assess the Pharmacokinetics of Vandetanib (CAPRELSA) in Healthy Subjects when a Single Oral Dose of Vandetanib 300 mg is Administered Alone and in Combination with Omeprazole or Ranitidine

Official Title
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A Phase I, Randomized, Open-label, Single-center Study to Assess the Pharmacokinetics of Vandetanib (CAPRELSA) in Healthy Subjects When a Single Oral Dose of Vandetanib 300 mg is Administered Alone and in Combination With Omeprazole or Ranitidine

Conditions
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Medullary Thyroid Cancer

Intervention / Treatment
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* Drug: vandetanib
* Drug: omeprazole
* Drug: ranitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study-specific procedures Volunteers must be males or females aged 18 to 50 years and with a weight of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2 Inclusive Females must have a negative pregnancy test at screening and on admission to the study center Females must not be lactating and must be of non childbearing potential defined as postmenopausal or documentation of irreversible surgical sterilization. Exclusion Criteria: History of any clinically significant disease or disorder such as gastrointestinal, hepatic, renal or skin disease. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity Volunteers who smoke more than 5 cigarettes per day or are unable to refrain from smoking while resident in the study center Screening blood pressure of greater than 140/90 mmHg and/or a resting heart rate of less than 45 beats per minute (repeat test allowed at the Investigator's discretion Clinically significant abnormal12-lead ECG as assessed by the Investigator QTcF interval greater than 450 ms Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody Human immunodeficiency virus (HIV), or positive screen for drugs of abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vandetanib then vandetanib + omeprazole<br>Vandetanib alone in period 1 followed by vandetanib in combination with omeprazole in period 2 | Drug: vandetanib<br>* Oral tablets, 300 mg, single dose<br>Drug: omeprazole<br>* Oral capsules, 40 mg, multiple doses<br>|
| Experimental: vandetanib + omeprazole then vandetanib<br>Vandetanib in combination with omeprazole in period 1 followed by vandetanib alone in period 2 | Drug: vandetanib<br>* Oral tablets, 300 mg, single dose<br>Drug: omeprazole<br>* Oral capsules, 40 mg, multiple doses<br>|
| Experimental: vandetanib then vandetanib + ranitidine<br>Vandetanib alone in period 1 followed by vandetanib in combination with ranitidine in period 2 | Drug: vandetanib<br>* Oral tablets, 300 mg, single dose<br>Drug: ranitidine<br>* Oral tables, 150 mg, multiple doses<br>|
| Experimental: vandetanib + ranitidine then vandetanib<br>Vandetanib in combination with ranitidine in period 1 followed by vandetanib alone in period 2 | Drug: vandetanib<br>* Oral tablets, 300 mg, single dose<br>Drug: ranitidine<br>* Oral tables, 150 mg, multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for a single dose of vandetanib alone and in combination with omeprazole (PPI) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 
| AUC(0-t) for a single dose of vandetanib alone and in combination with omeprazole (PPI) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 
| Cmax for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 
| AUC(0-t) for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events |  | Treatment period + 7-14 days | 
| ECG data |  | Treatment period + 7-14 days | 
| Laboratory data |  | Treatment period + 7-14 days | 
| Vital signs data |  | Treatment period + 7-14 days | 
| Other PK parameters for a single dose of vandetanib alone and in combination with omeprazole (PPI) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 
| Other PK parameters for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist) |  | Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, healthy volunteers, pharmacokinetics, vandetanib, omeprazole, ranitidine