A Phase I Study to Assess the Pharmacokinetics of Metformin When Administered Alone and in Combination With Vandetanib

Study Overview
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Brief Summary
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Study in Healthy Volunteers to Assess the Pharmacokinetics of Metformin 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 Metformin, an OCT2 Substrate, in Healthy Subjects When administered Alone and in Combination with a Single Oral Dose of Vandetanib (CAPRELSA) 800 mg

Official Title
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A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Metformin, an OCT2 Substrate, in Healthy Subjects When Administered Alone and in Combination With a Single Oral Dose of Vandetanib (CAPRELSA) 800 mg

Conditions
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Healthy

Intervention / Treatment
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* Drug: Metformin 1000 mg
* Drug: Vandetanib 800 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females aged 18 to 50 years with a weight of at least 50 kg and a body mass index between 18 and 30 kg/m2 inclusive. Females must have a negative pregnancy test at screening, must not be lactating and must be of non-childbearing potential. Volunteers will be wild type for the OCT2 gene (as tested for within the last 6 months prior to Day 1 in Period 1) Exclusion Criteria: History or presence of gastrointestinal, hepatic, or renal disease or any medically significant disorder. History of or ongoing severe allergy/hypersensitivity to drugs with a similar chemical structure or class to vandetanib or metformin. Volunteers who smoke more than 5 cigarettes per day or are unable to refrain from smoking while resident in the study center. Known or suspected history of drug abuse. Screening supine blood pressure of greater than 140/90 mmHg and/or a resting heart rate of less than 45 beats per minute. Clinically significant current active skin disease (eg moderate to severe acne, psoriasis, eczema). Any positive result on screening for serum hepatitis B, surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin then metformin + vandetanib<br>Metformin alone followed by metformin in combination with vandetanib | Drug: Metformin 1000 mg<br>* 2 x 500 mg oral tablets<br>Drug: Vandetanib 800 mg<br>* 2 x 300 mg and 2 x 100 mg oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC for metformin administered alone and in combination with vandetanib 800 mg |  | Period 1: Predose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours post dose. Period 2: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours post-dose. | 
| Cmax for metformin administered alone and in combination with vandetanib 800 mg |  | Period 1: Predose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours post dose. Period 2: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours 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 metformin administered alone and in combination with vandetanib 800 mg |  | Period 1: Predose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours post dose. Period 2: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 96 hours post-dose. | 
| Vandetanib PK parameters for vandetanib in combination with metformin |  | Period 2: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36, 48, 72, 96, 168, 240, 336, 504, and 672 hours post-dose. | 
| PK parameters for metformin in urine when administered alone and in combination with vandetanib |  | Period 1: Day 1, 0 to 24 hrs and 24 to 48 hrs post metformin dose. Period 2: Day 1, 0 to 24 hrs and 24 to 48 hrs post metformin 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, metformin, AUC(0-t), t1/2, tmax, CL/F, Vz/F, Cmax