Metabolism and Excretion of [14C]-Rigosertib After Infusion to Volunteers

NCT02030639 | Completed Phase 1

• 2 other identifiers: Onconova 04-238287875
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• The mean percent of the radioactivity of the administered doses recovered in the urine, feces, and overall (urine + feces)

  Urine sample collection for radio analysis will be over the intervals of 24-30 hours (hr), 30-36 hr, 36-42 hr, 42-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, and if necessary based on discharge criteria, at 120-144 hr, 144-168 hr, 168-192 hr, and 192-216 hr after the infusion start. Fecal sample collection for radio analysis will be over the intervals of 24-30 hr, 30-36 hr, 36-42 hr, 42-48 hr, 48-72 hr, 72-96 hr, 96-120 hr, and if necessary based on discharge criteria, at 120-144 hr, 144-168 hr, 168-192 hr, and 192-216 hr after the infusion start.

  Up to 216 hours

• Concentration of rigosertib in plasma

  Concentration of rigosertib in plasma will be measured by a validated high performance liquid chromatography (HPLC) method. Plasma samples will be collected at 24 hours (hr) (immediately before the end of the infusion), 24.25 hr, 24.5 hr, 25 hr, 26 hr, 28 hr, 30 hr, 36 hr, 48 hr, 72 hr, and 96 hr after the infusion start, and, if the subject has not been discharged by then, at 144 hr, 192 hr, and 216 hr after the infusion start. Concentration values will be used to derive the following pharmacokinetic parameters: Cmax; tmax; AUC0-t; AUC0-∞; λZ; t1/2; CL; Vz; Vss.

  Up to 216 hours

• Concentration of radioactivity in whole blood

  Blood samples for radio analysis will be collected at 24 hours (hr) (immediately before the end of the infusion), 24.25 hr, 24.5 hr, 25 hr, 26 hr, 28 hr, 30 hr, 36 hr, 48 hr, 72 hr, and 96 hr after the infusion start, and, if the subject has not been discharged by then, at 144 hr, 192 hr, and 216 hr after the infusion start.

  Up to 216 hours

• Concentration of radioactivity in plasma

  Plasma samples for radio analysis will be collected at 24 hours (hr) (immediately before the end of the infusion), 24.25 hr, 24.5 hr, 25 hr, 26 hr, 28 hr, 30 hr, 36 hr, 48 hr, 72 hr, and 96 hr after the infusion start, and, if the subject has not been discharged by then, at 144 hr, 192 hr, and 216 hr after the infusion start.

  Up to 216 hour

Secondary Outcomes (5)

• Metabolite profiling

  Up to 216 hours

• Metabolite identification

  Up to 216 hours

• Concentration of radioactivity in urine

  Up to 216 hours

• Concentration of radioactivity in feces

  Up to 216 hours

• Number of subjects who experience an adverse event

  Up to 31 days

Study Arms (1)

[14C]-rigosertib

EXPERIMENTAL

A single dose of 450 mg of rigosertib containing 250 microcuries of carbon 14-labeled rigosertib (\[14C\]-rigosertib) administered as a continuous intravenous (CIV) infusion over 24 hours to healthy volunteers.

Drug: rigosertib

Interventions

rigosertib DRUG

A single dose of 450 mg of rigosertib containing 250 microcuries of carbon 14-labeled rigosertib (\[14C\]-rigosertib) administered as a continuous intravenous (CIV) infusion over 24 hours to healthy volunteers.

Also known as: rigosertib sodium, ON 01910.Na

[14C]-rigosertib

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Covance Clinical Research Unit, Inc.

Madison, Wisconsin, 53704, United States

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Interventions

ON 01910

Study Officials

• Francois Wilhelm, MD, PhD

  Traws Pharma, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 8, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: August 1, 2015
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (1)