Clinical trial NCT01561781: Study in Healthy Volunteers to Assess the Pharmacokinetics (PK) of Digoxin Administered Alone and in Combination With Vandetanib
Official title: A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination With a Single Dose of Vandetanib (CAPRELSA) 300 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase 1
healthy volunteers
pharmacokinetics
vandetanib
digoxin
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-03-23
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a study in healthy volunteers to assess the pharmacokinetics (PK) of Digoxin administered alone and in combination with Vandetanib.

Detailed description: A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination with a Single Dose of Vandetanib (CAPRELSA) 300 mg

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 45 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 are current smokers and have smoked or used nicotine products within the previous 6 months
* 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, and human immunodeficiency virus (HIV), or positive screen for drugs of abuse.

Primary outcomes:
measure: AUC for digoxin administered alone and in combination with vandetanib 300 mg
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 hrs post dose
measure: Cmax for digoxin administered alone and in combination with vandetanib 300 mg
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 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 digoxin administered alone and in combination with vandetanib 300 mg
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12, 18, 30, 48, 72, 96, 120, 144, and 168 hrs post dose
measure: Digoxin PK parameters for vandetanib in combination with digoxin
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 48, 72, and 96 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.