Study in Healthy Volunteers to Assess the Pharmacokinetics (PK) of Digoxin Administered Alone and in Combination With Vandetanib

Study Overview
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Brief Summary
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This is a study in healthy volunteers to assess the pharmacokinetics (PK) of Digoxin administered alone and in combination with Vandetanib.

Detailed Description
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A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination with a Single Dose of Vandetanib (CAPRELSA) 300 mg

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Digoxin
* Drug: Vandetanib


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 45 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 are current smokers and have smoked or used nicotine products within the previous 6 months 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, and 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: 45 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: digoxin then digoxin + vandetanib<br>Digoxin alone followed by digoxin in combination with vandetanib | Drug: Digoxin<br>* Oral tablets 0.25mg, single dose<br>Drug: Vandetanib<br>* Oral tablets, 300 mg, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC for digoxin administered alone and in combination with vandetanib 300 mg |  | Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 hrs post dose | 
| Cmax for digoxin administered alone and in combination with vandetanib 300 mg |  | Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 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 digoxin administered alone and in combination with vandetanib 300 mg |  | Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 hrs post dose | 
| Digoxin PK parameters for vandetanib in combination with digoxin |  | Predose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 48, 72, and 96 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, digoxin