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

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: Metformin 1000 mg Drug: Vandetanib 800 mg	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Metformin Metformin hydrochloride Vandetanib

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

AUC for metformin administered alone and in combination with vandetanib 800 mg [ Time Frame: 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. ] [ Designated as safety issue: No ]
Cmax for metformin administered alone and in combination with vandetanib 800 mg [ Time Frame: 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Frequency and severity of adverse events [ Time Frame: Treatment period 7-14 days ] [ Designated as safety issue: Yes ]
ECG data [ Time Frame: Treatment period 7-14 days ] [ Designated as safety issue: Yes ]
Laboratory data [ Time Frame: Treatment period 7-14 days ] [ Designated as safety issue: Yes ]
Vital signs data [ Time Frame: Treatment period 7-14 days ] [ Designated as safety issue: Yes ]
Other PK parameters for metformin administered alone and in combination with vandetanib 800 mg [ Time Frame: 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. ] [ Designated as safety issue: No ]
Vandetanib PK parameters for vandetanib in combination with metformin [ Time Frame: 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. ] [ Designated as safety issue: No ]
PK parameters for metformin in urine when administered alone and in combination with vandetanib [ Time Frame: 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. ] [ Designated as safety issue: No ]

Enrollment:	14
Study Start Date:	March 2012
Study Completion Date:	June 2012
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551615

Locations

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

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	James Vaselli, Medical Science Director	AstraZeneca
Principal Investigator:	David Mathews, MD	Quintiles

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01551615 History of Changes
Other Study ID Numbers:	D4200C00102
Study First Received:	March 5, 2012
Last Updated:	June 22, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Phase 1
healthy volunteers
pharmacokinetics
vandetanib
metformin
AUC(0-t)

t1/2
tmax
CL/F
Vz/F
Cmax

Additional relevant MeSH terms:

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013