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

Phase 1
Completed
Conditions
Healthy
Interventions
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

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
GroupInterventionDescription
Metformin then metformin + vandetanibVandetanib 800 mgMetformin alone followed by metformin in combination with vandetanib
Metformin then metformin + vandetanibMetformin 1000 mgMetformin alone followed by metformin in combination with vandetanib
Primary Outcome Measures
NameTimeMethod
AUC for metformin administered alone and in combination with vandetanib 800 mgPeriod 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 mgPeriod 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
NameTimeMethod
Frequency and severity of adverse eventsTreatment period 7-14 days
Laboratory dataTreatment period 7-14 days
Vital signs dataTreatment period 7-14 days
PK parameters for metformin in urine when administered alone and in combination with vandetanibPeriod 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 dataTreatment period 7-14 days
Vandetanib PK parameters for vandetanib in combination with metforminPeriod 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 mgPeriod 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

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