Primary: * To determine the effect of food on the bioavailability of E7050 following oral administration of a tablet containing 100 mg E7050 with and without a standard low- or high-fat breakfast (Part A)* To characterize E7050 pharmacokinetics…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics:
plasma and urine E7050 concentrations, pharmacokinetic parameters
Secondary outcome
Safety:
adverse events, vital signs, ECG-parameters, laboratory parameters, physical
examination
Background summary
E7050 is a new, investigational drug that may eventually be used for the
treatment of different types of cancer. The study drug is expected to stop the
cell growth of certain cancer cells; this action has been shown in early animal
studies.
E7050 is a new chemical entity, an inhibitor of multi-targeted receptor
tyrosine kinase that potently inhibits c-Met kinase. E7050 selectively inhibits
cell growth of c-Met amplified cancer cell lines and HGF-induced proliferation
of cancer cell lines, in which c-Met kinase signal is activated. E7050 also
inhibits VEGFR-2 kinase and VEGF-induced cell growth of human umbilical vein
endothelial cells at slightly higher IC50 compared to inhibition of c-Met.
Study objective
Primary:
* To determine the effect of food on the bioavailability of E7050 following
oral administration of a tablet containing 100 mg E7050 with and without a
standard low- or high-fat breakfast (Part A)
* To characterize E7050 pharmacokinetics after single doses at 200 mg and 400
mg under fasted conditions (Part B)
Secondary:
* To evaluate the safety in healthy subjects with single doses of 100 mg E7050
(formulated as a tablet) administered with and without a standard low- or
high-fat breakfast (Part A) and after single doses of 200 and 400 mg
administered in the fasted state (Part B).
EXPLORATORY OBJECTIVE(S)
* To evaluate the role of DNA sequence variability on ADME.
Study design
Design:
The study will consist of two parts:
Part A (Food Effect) and Part B (E7050 PK characterization after a single oral
dose of 200 or 400 mg E7050)
Part A will be a randomized, single-dose, open-label, three period crossover
study. It will consist of 2 phases: Prerandomization and Randomization. The
Prerandomization Phase will have two periods: Screening and Baseline. The
Randomization Phase will have 5 periods: Period 1, Baseline + Period 2, and
Baseline + Period 3. Just prior to the Randomization Phase, 18 subjects will be
randomized to one of six possible sequences (ABC, ACB, BAC, BCA, CAB and CBA).
In each period, subjects will receive a single tablet containing 100 mg E7050
either following an overnight fast (A), with a standard low-fat meal (B), or
with a standard high-fat meal (C). There will be a 2-week washout between the
periods.
Part B will begin approximately 2 weeks after Period 1 of Part A is complete
and once all safety data has been evaluated. It will be conducted as a
randomized, open-label, two-period parallel study design with two phases: a
Prerandomization Phase consisting of a Screening and Baseline period and a
Randomization Phase with 1 period (Treatment Period). Just prior to the
Randomization Phase, 24 subjects will be randomized equally to receive either
200 mg (D) or 400 mg (E) of E7050 under fasted conditions.
Procedures and assessments
Screening and follow-up:
clinical laboratory, vital signs (including respiratory rate and body
temperature), physical examination, 12-lead ECG, serum pregnancy test (females
only; at eligibility screening: medical history, genomic DNA sample, urine drug
screen, urine alcohol screen, HBsAg, anti HCV, anti-HIV 1/2; physical
examination, vital signs (including respiratory rate and body temperature),
12-lead ECG, urine drug screen, urine pregnancy test and clinical laboratory to
be repeated upon (each) admission; follow-up on Day 37 (Part A) and Day 9 (Part
B)
Part A (FE):
observation period:
3 periods, first period in clinic from -17 h up to 168 h after drug
administration on Day 1, second period in clinic from -17 h up to 168 h after
drug administration on Day 15 and third period in clinic from -17 h up to 168 h
after drug administration on Day 29
Blood sampling:
for pharmacokinetics of E7050: pre-dose and 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48,
72, 96, 120, 144 and 168 h post-dose on Days 1, 15 and 29
Urine Sampling:
for pharmacokinetics of E7050: pre-dose and intervals 0-4, 4-8, 8-12 and 12-24
h post-dose on Days 1, 15 and 29
Safety Assessments:
adverse events: throughout the study; physical examination: once on Days 1, 15
and 29; vital signs (including respiratory rate and body temperature): pre-dose
and 1, 2, 3, 4, 8 and 16 h post-dose on Days 1, 15 and 29
Part B (SAD)
Observation period:
one period in clinic from -17 h up to 168 h after drug administration
Blood sampling
for pharmacokinetics of E7050: pre-dose and 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48,
72, 96, 120, 144 and 168 h post-dose
Urine sampling:
for pharmacokinetics of E7050: pre-dose and intervals 0-4, 4-8, 8-12 and 12-24
h post-dose
Safety assessments:
adverse events: throughout the study; physical examination: once on Day 1;
vital signs (including respiratory rate and body temperature): pre-dose and 1,
2, 3, 4, 8 and 16 h post-dose on Day 1.
Bioanalysis:
analysis of plasma and urine E7050 samples using validated methods by Sponsor
genotyping by Sponsor
Intervention
Part A
Treatment A: a single oral dose of 100 mg E7050 in the fasted state
Treatment B: a single oral dose of 100 mg E7050 in the fed state (low fat
breakfast)
Treatment C: a single oral dose of 100 mg E7050 in the fed state (high-fat
breakfast)
Part B
Treatment D: a single oral dose of 200 mg E7050 in the fasted state
Treatment E: a single oral dose of 400 mg E7050 in the fasted state
Study burden and risks
Procedures:
Pain, light bleeding, heamatoma, possibly an infection.
European Knowledge Centre, Mosquito Way
AL10 9SN, Hatfield
GB
European Knowledge Centre, Mosquito Way
AL10 9SN, Hatfield
GB
Listed location countries
Age
Inclusion criteria
* between 18 and 45 years of age
* BMI between 18 and 32 kg/m2
* non-smoker
* at screening state of health must satisfy the entry requirements
Exclusion criteria
1. Evidence of clinically significant cardiovascular, hepatic, gastrointestinal, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities or a known history of any gastrointestinal surgery that could impact the pharmacokinetics of study drug.
2. Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks of dosing.
3. Evidence of organ dysfunction or any clinically significant deviation from normal in their medical history.
4. Evidence of clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory determinations at Screening or Baseline.
5. A QTcF interval > 450 msec at Screening or Baseline, or 30 seconds before administration of study drug.
6. Females who are either pregnant or lactating.
7. A known or suspected history of drug or alcohol abuse within 6 months prior to screening, or who have a positive urine drug test or alcohol test at Screening or Baseline.
8. Positive results for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV) screen.
9. Diagnosis of acquired immune deficiency syndrome (AIDS), or positive test for human immunodeficiency virus (HIV).
10. Participation in another clinical trial less than 4 weeks prior to dosing or current enrollment in another clinical trial.
11. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week prior to dosing.
12. Hemoglobin level < 12.0 g/dL.
13. Known history of any significant drug or food allergy or an ongoing seasonal allergy.
14. Use of prescription drugs within 2 weeks prior to Screening (unless drug has a long t*, i.e., 5x t* exceeds 2 weeks).
15. Use of over-the-counter (OTC) medications within a minimum of 2 weeks prior to dosing.
16. Requiring a special diet or taking dietary aids known to modulate drug metabolizing enzymes, or who have consumed foods/beverages or herbal preparations containing Kava root, Ginkgo Biloba Extract (GBE), or St John*s Wort within 4 weeks of Baseline Period 1.
17. Known intolerance to the study drug (or any of the excipients).
18. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022185-27-NL |
| CCMO | NL33785.056.10 |