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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01551615
First received: March 5, 2012
Last updated: August 14, 2014
Last verified: August 2014
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Additional 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: August 14, 2014
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
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014