Study in Healthy Volunteers to Assess Effect of Omeprazole and Ranitidine on the Pharmacokinetics of Vandetanib (Vandetanib)

A Phase I, Randomized, Open-label, Single-center Study to Assess the Pharmacokinetics of Vandetanib (CAPRELSA) in Healthy Subjects When a Single Oral Dose of Vandetanib 300 mg is Administered Alone and in Combination With Omeprazole or Ranitidine

Study in healthy volunteers to assess effect of omeprazole and ranitidine on the pharmacokinetics of vandetanib

Study Overview

• Status: Completed
• Conditions: Medullary Thyroid Cancer
• Intervention / Treatment: Drug: vandetanib; Drug: omeprazole; Drug: ranitidine

Detailed Description

A Phase I, Randomized, Open-label, Single-center Study to Assess the Pharmacokinetics of Vandetanib (CAPRELSA) in Healthy Subjects when a Single Oral Dose of Vandetanib 300 mg is Administered Alone and in Combination with Omeprazole or Ranitidine

• Study Type: Interventional
• Enrollment (Actual): 34
• 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:

• Provision of signed and dated, written informed consent prior to any study-specific procedures
• Volunteers must be males or females aged 18 to 50 years and with a weight of at least 50 kg and body mass index (BMI) between 18 and 30 kg/m2
• Inclusive Females must have a negative pregnancy test at screening and on admission to the study center
• Females must not be lactating and must be of non childbearing potential defined as postmenopausal or documentation of irreversible surgical sterilization.

Exclusion Criteria:

• History of any clinically significant disease or disorder such as gastrointestinal, hepatic, renal or skin disease.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity
• Volunteers who smoke more than 5 cigarettes per day or are unable to refrain from smoking while resident in the study center
• Screening blood pressure of greater than 140/90 mmHg and/or a resting heart rate of less than 45 beats per minute (repeat test allowed at the Investigator's discretion
• Clinically significant abnormal12-lead ECG as assessed by the Investigator
• QTcF interval greater than 450 ms Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody
• Human immunodeficiency virus (HIV), or positive screen for drugs of abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: vandetanib then vandetanib + omeprazole; Vandetanib alone in period 1 followed by vandetanib in combination with omeprazole in period 2	Drug: vandetanib; Oral tablets, 300 mg, single dose; Drug: omeprazole; Oral capsules, 40 mg, multiple doses
EXPERIMENTAL: vandetanib + omeprazole then vandetanib; Vandetanib in combination with omeprazole in period 1 followed by vandetanib alone in period 2	Drug: vandetanib; Oral tablets, 300 mg, single dose; Drug: omeprazole; Oral capsules, 40 mg, multiple doses
EXPERIMENTAL: vandetanib then vandetanib + ranitidine; Vandetanib alone in period 1 followed by vandetanib in combination with ranitidine in period 2	Drug: vandetanib; Oral tablets, 300 mg, single dose; Drug: ranitidine; Oral tables, 150 mg, multiple doses
EXPERIMENTAL: vandetanib + ranitidine then vandetanib; Vandetanib in combination with ranitidine in period 1 followed by vandetanib alone in period 2	Drug: vandetanib; Oral tablets, 300 mg, single dose; Drug: ranitidine; Oral tables, 150 mg, multiple doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax for a single dose of vandetanib alone and in combination with omeprazole (PPI)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose
AUC(0-t) for a single dose of vandetanib alone and in combination with omeprazole (PPI)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose
Cmax for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose
AUC(0-t) for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs 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 a single dose of vandetanib alone and in combination with omeprazole (PPI)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post dose
Other PK parameters for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)	Predose,1,2,3,4,5,6,7,8,10,12,18,24,36,48,72,96,120,144,168,192,216,240,336,504 ,672 hrs post 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-D4200C00101.pdf
• Revised_CSP_redacted

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: February 10, 2012
• First Submitted That Met QC Criteria: February 22, 2012
• First Posted (ESTIMATE): February 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2017
• Last Update Submitted That Met QC Criteria: April 28, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; healthy volunteers; omeprazole; ranitidine; vandetanib
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Omeprazole; Ranitidine; Ranitidine bismuth citrate
• Other Study ID Numbers: D4200C00101