Healthy
Conditions
Keywords
Phase 1, healthy volunteers, pharmacokinetics, vandetanib, metformin, AUC(0-t), t1/2, tmax, CL/F, Vz/F, Cmax
Brief summary
Study in Healthy Volunteers to Assess the Pharmacokinetics of Metformin Administered Alone and In Combination with Vandetanib
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
Interventions
2 x 500 mg oral tablets
DRUGVandetanib 800 mg
2 x 300 mg and 2 x 100 mg oral tablets
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC for metformin administered alone and in combination with vandetanib 800 mg | 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. |
| Cmax for metformin administered alone and in combination with vandetanib 800 mg | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Laboratory data | Treatment period 7-14 days |
| Vital signs data | Treatment period 7-14 days |
| Frequency and severity of adverse events | Treatment period 7-14 days |
| Vandetanib PK parameters for vandetanib in combination with metformin | 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. |
| PK parameters for metformin in urine when administered alone and in combination with vandetanib | 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. |
| Other PK parameters for metformin administered alone and in combination with vandetanib 800 mg | 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. |
| ECG data | Treatment period 7-14 days |
Countries
United States
Outcome results
None listed