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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Metformin 1000 mg; Drug: Vandetanib 800 mg

• Registration Number: NCT01551615
• Lead Sponsor: Sanofi

Brief Summary

Study in Healthy Volunteers to Assess the Pharmacokinetics of Metformin Administered Alone and In Combination with Vandetanib

Detailed Description

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

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-03-05
• Study First Submitted QC: 2012-03-12
• Study First Posted: 2012-03-13
• Primary Completion: 2012-06
• Study Completion: 2012-06
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-26
• Last Update Posted: 2016-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin then metformin + vandetanib	Vandetanib 800 mg	Metformin alone followed by metformin in combination with vandetanib
Metformin then metformin + vandetanib	Metformin 1000 mg	Metformin alone followed by metformin in combination with vandetanib

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Frequency and severity of adverse events	Treatment period 7-14 days
Laboratory data	Treatment period 7-14 days
Vital signs data	Treatment period 7-14 days
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.
ECG data	Treatment period 7-14 days
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.
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.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Overland Park, Kansas, United States