Clinical trial NCT02030639: Metabolism and Excretion of [14C]-Rigosertib After Infusion to Volunteers
Official title: Phase I Study of the Metabolism and Excretion of [14C]-Rigosertib After Single-dose Administration as 24-hour Continuous Intravenous Infusion to Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Traws Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to gain an understanding of how the experimental anti-cancer drug, rigosertib, is metabolized in the body and excreted in the urine and feces after it is given as an intravenous infusion. In addition, the study will be carefully monitored to see if any side effects occur.

A radioactive drug is used in this study because it is easier and more accurate to measure radioactivity than to use more complicated and less sensitive chemical tests for the drug.

Detailed description: This study will be an open-label, non-randomized, metabolism and excretion study of \[14C\]-rigosertib administered as a single dose of approximately 450 mg containing 250 μCi \[14C\]-labeled rigosertib as a 24-hour continuous intravenous (CIV) infusion in healthy volunteers. Up to 8 subjects will be enrolled to ensure at least 6 subjects have evaluable data.

Eligible subjects will be confined at the clinical site from the time of Check-in (approximately 24 hours prior to dosing) until Discharge (between Days 6 and 10). One single dose of \[14C\]-rigosertib will be administered as a 24-hour continuous intravenous infusion on Day 1. Subjects will be discharged as early as 120 hours after the start of the infusion, after ≥ 90% of the administered radioactive dose has been recovered in urine and feces or when the combined total radioactivity recovered in urine and feces is ≤ 1% of the administered radioactive dose for 2 consecutive 24-hr samples. The maximum stay will be until Day 10 (216 hours after the start of the infusion).

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) between 18.5 kg/m2 and 29.9 kg/m2, inclusive;
* In good health, as defined by the absence of clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs;
* Clinical laboratory evaluations that are within the normal range, unless deemed not clinically significant by the Investigator. Platelet (PLT) count, white blood cell (WBC) count, and absolute neutrophil count (ANC) should all be above the lower limit of normal (LLN);
* Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (does include alcohol);
* Negative hepatitis panel (including hepatitis B surface antigen \[HBsAg\] and hepatitis C virus antibody \[anti-HCV\]) and negative human immunodeficiency virus (HIV) antibody screens;
* Males will either be vasectomized or sterile;
* Female subjects must have undergone confirmed tubal ligation or hysterectomy or be post-menopausal;
* Able to comprehend and willing to sign an informed consent form (ICF);
* History of a minimum of 1 bowel movement per day.

Exclusion Criteria:

* Participation in any other investigational study drug trial in which receipt of an investigational agent, biologic agent, small targeted molecule, or immunotherapy occurred within 5 half-lives or 4 weeks of enrollment, whichever is longer;
* Major surgery within 3 weeks of enrollment or major surgery without full recovery;
* History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed;
* Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder;
* History of Gilbert's Syndrome;
* History or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant;
* Uncontrolled hypertension, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, unless deemed acceptable by the Investigator;
* History of seizures, except febrile seizures as a child;
* Psychiatric illness/social situations that would limit the subject's ability to tolerate and/or comply with study requirements, or inability to comply with study and/or follow-up procedures;
* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator;
* History of alcoholism or drug addiction within 1 year prior to Check-in;
* Participation in more than 1 other radiolabeled investigational study drug trial within 12 months prior to Check-in. The previous radiolabeled study drug must have been received more than 6 months prior to Check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe;
* Exposure to significant radiation within 12 months prior to Check-in;
* Use of any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator;
* Use of any over-the-counter, non-prescription preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator;
* Poor peripheral venous access;
* Donation of blood from 30 days prior to Screening through discharge, inclusive, or of plasma from 2 weeks prior to Screening through discharge, inclusive;
* Receipt of blood products within 2 months prior to Check-in;
* Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study.

Primary outcomes:
measure: The mean percent of the radioactivity of the administered doses recovered in the urine, feces, and overall (urine + feces)
timeFrame: Up to 216 hours
measure: Concentration of rigosertib in plasma
timeFrame: Up to 216 hours
measure: Concentration of radioactivity in whole blood
timeFrame: Up to 216 hours
measure: Concentration of radioactivity in plasma
timeFrame: Up to 216 hour
Secondary outcomes:
measure: Metabolite profiling
timeFrame: Up to 216 hours
measure: Metabolite identification
timeFrame: Up to 216 hours
measure: Concentration of radioactivity in urine
timeFrame: Up to 216 hours
measure: Concentration of radioactivity in feces
timeFrame: Up to 216 hours
measure: Number of subjects who experience an adverse event
timeFrame: Up to 31 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Wisconsin
Study officials:
affiliation: Traws Pharma, Inc.
name: Francois Wilhelm, MD, PhD
role: STUDY_CHAIR
References:
citation: Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.