Primary objectives:To identify and quantify the excretion pathways of oral ASTX029, including the mass balance and the excretions in urine and feces (Period 1).To determine the absolute oral bioavailability (F) of ASTX029 under fasting conditions (…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
advanced solid tumors
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• The amount of radioactivity excreted in urine and feces with an objective to
recover >=90% of the radiolabeled ASTX026.
Secondary outcome
• Concentration-time profile and PK parameters of total radioactivity from
analysis of plasma, urine, and feces collected at identified timepoints.
• PK parameter estimates for ASTX026 in plasma.
• [14C]-metabolic profile and identified metabolites in plasma blood.
• Major radioactive peak/metabolites in the urine and fecal radiochromatograms
as a percentage of the radioactive dose.
• Incidence and severity of treatment emergent adverse events (TEAEs).
Background summary
ASTX029 is a synthetic small molecule that acts as an inhibitor of the
extracellular signal-regulated kinases (ERK) 1/2, which are serine/threonine
kinases that comprise a key component of the mitogen-activated protein kinase
(MAPK) signaling pathway.
ERK activity is commonly upregulated in cancer, as a result of activating
mutations within upstream components of the MAPK pathway, such as rat sarcoma
virus (RAS) and Rapidly accelerated fibrosarcoma (RAF).
ASTX029 has been evaluated comprehensively in preclinical toxicology studies
and has not shown unacceptable toxicities. ASTX029 was also negative in
genotoxicity panel including Ames assay, chromosomal aberration and in vivo
micronucleus assay. For more details on the pre-clinical and clinical studies
conducted with ASTX029, please see the Investigator*s Brochure.
Study objective
Primary objectives:
To identify and quantify the excretion pathways of oral ASTX029, including the
mass balance and the excretions in urine and feces (Period 1).
To determine the absolute oral bioavailability (F) of ASTX029 under fasting
conditions (Period 2).
Secondary objectives:
To determine the fraction of an ASTX029 oral dose absorbed (Fa).
To determine the plasma and urine pharmacokinetics (PK) of ASTX029 following
oral and intravenous (IV) administration of 14C-ASTX029.
To determine the safety and tolerability of ASTX029 following the sequential
oral and IV administrations of non-radiolabeled and 14C-ASTX029, respectively.
To identify and quantify the metabolites of ASTX029, if feasible.
Study design
Phase 1 open-label, 2-treatment period fixed-sequence study of single doses of
ASTX029 in healthy subjects.
Intervention
IMP and formulations: 14C-ASTX029 solution, 14C-ASTX029 IV formulation and
ASTX029 tablet
Route of Administration: Oral (tablet and solution) and intravenously (IV)
(solution) administration
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the overall benefit risk in the CSP
for further information.
4420 Rosewood Drive Suite 200
Pleasanton CA 94588
US
4420 Rosewood Drive Suite 200
Pleasanton CA 94588
US
Listed location countries
Age
Inclusion criteria
1. Male subjects and female subjects of non-childbearing potential , aged 18
years to 65 years, inclusive, at Screening.
2. Body mass index (BMI) of 18.0 kg/m2 to 32.0 kg/m2, inclusive, and at
Screening.
3. Women of non-childbearing potential should be surgically sterilized or
physiologically incapable of becoming pregnant or should be postmenopausal.
Surgically sterile women are defined as those who have had a hysterectomy,
bilateral ovariectomy, or bilateral tubal ligation. Women who are surgically
sterile must provide documentation of the procedure. Postmenopausal women must
have had >=12 months of spontaneous amenorrhea (with documented
follicle-stimulating hormone (FSH) >=33.4 mIU/mL). All women must have a
negative pregnancy test result at Screening and on Day -1 of Period 1.
4. Male subjects, if not surgically sterilized, must agree to use adequate
contraception and not donate sperm from first admission to the clinical
research center until 90 days after the follow-up visit. Adequate contraception
for male subjects who are sexually active with women of childbearing potential
(WOCBP) entails the use of a latex or other synthetic condom during any sexual
activity with WOCBP until 90 days after the follow-up visit. Total abstinence,
in accordance with the lifestyle of the subject, is also acceptable.
5. Satisfactory physical and mental health at Screening and on Day -1 on the
basis of medical history, physical examination, clinical laboratory, 12-lead
electrocardiogram (ECG) in triplicate, and vital signs, as judged by the
Principal Investigator.
Exclusion criteria
1. Employee of clinical research organization (CRO) or the Sponsor.
2. Clinically significant systemic allergic disease or a history of significant
drug and/or food allergies, including, but not limited to, a history of
anaphylactic reactions, or allergic reactions due to any drug and/or food
leading to significant morbidity.
3. Use of any prescription drugs within 30 days or 5 half-lives (whichever is
longer) prior to each admission to the clinic.
4. Use of any non-prescription drugs (excluding paracetamol), vitamin
preparations and other food supplements, or herbal medications (eg, St John*s
Wort) within 14 days prior to each admission to the clinic.
Design
Recruitment
Medical products/devices used
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 | EUCTR2022-002656-39-NL |
| CCMO | NL82249.056.22 |