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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Metformin 1000 mg; Drug: Vandetanib 800 mg

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Johansson S, Read J, Oliver S, Steinberg M, Li Y, Lisbon E, Mathews D, Leese PT, Martin P. Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Clin Pharmacokinet. 2014 Sep;53(9):837-47. doi: 10.1007/s40262-014-0161-2. Erratum In: Clin Pharmacokinet. 2014 Nov;53(11):1063.

Helpful Links

• Related Info
• CSR-D4200C00102.pdf
• Revised_CSP_redacted

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 5, 2012
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Estimate): August 29, 2016
• Last Update Submitted That Met QC Criteria: August 26, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; tmax; metformin; healthy volunteers; Cmax; AUC(0-t); vandetanib; t1/2; CL/F; Vz/F
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: D4200C00102