Clinical trial NCT01539655: Study in Healthy Volunteers to Assess Effect of Omeprazole and Ranitidine on the Pharmacokinetics of Vandetanib
Official title: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Medullary Thyroid Cancer
Keywords: Phase 1
healthy volunteers
pharmacokinetics
vandetanib
omeprazole
ranitidine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-02-27
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax for a single dose of vandetanib alone and in combination with omeprazole (PPI)
timeFrame: 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
measure: AUC(0-t) for a single dose of vandetanib alone and in combination with omeprazole (PPI)
timeFrame: 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
measure: Cmax for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)
timeFrame: 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
measure: AUC(0-t) for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)
timeFrame: 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 outcomes:
measure: Frequency and severity of adverse events
timeFrame: Treatment period + 7-14 days
measure: ECG data
timeFrame: Treatment period + 7-14 days
measure: Laboratory data
timeFrame: Treatment period + 7-14 days
measure: Vital signs data
timeFrame: Treatment period + 7-14 days
measure: Other PK parameters for a single dose of vandetanib alone and in combination with omeprazole (PPI)
timeFrame: 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
measure: Other PK parameters for a single dose of vandetanib alone and in combination with ranitidine (histamine antagonist)
timeFrame: 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 outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.