HealthyPhase 1NCT02030639
Metabolism and Excretion of [14C]-Rigosertib After Infusion to Volunteers
A Phase 1 study testing rigosertib in people with Healthy, run by Traws Pharma, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- rigosertib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Aug 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Covance Clinical Research Unit, Inc.
Madison, Wisconsin, 53704
About this study
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
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.
Read the 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).
- Conditions
- Healthy
- Being tested
- rigosertib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rigosertibDrug
Also called rigosertib sodium, ON 01910.Na
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.
| Study group | Role | What they receive |
|---|---|---|
| [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. Receives: Drug: rigosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 216 hour
Secondary outcomes (5)
Metabolite profiling
Extracts from samples of plasma, urine and feces will be subjected to high performance liquid chromatography (HPLC) with radiochemical detection for the quantitative analysis of rigosertib and its metabolites.
Measured: Up to 216 hours
Metabolite identification
Metabolite identification will be carried out by mass spectrometry. Synthetic standards of known metabolites will be used to confirm identifications.
Measured: Up to 216 hours
Concentration of radioactivity in urine
Urine 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.
Measured: Up to 216 hours
Concentration of radioactivity in feces
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.
Measured: Up to 216 hours
Number of subjects who experience an adverse event
An adverse event is defined according to ICH E2A guidance.
Measured: Up to 31 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionDec 2014
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Francois Wilhelm, MD, PhD, Study chair, Traws Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030639
- Sponsor's protocol ID
- Onconova 04-23
- Other IDs
- 8287875
- Status last verified
- Jun 2017
- First submitted
- 7 Jan 2014
- Last updated
- 23 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02030639
- Acronym / sponsor ID
- Onconova 04-23
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 8 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [14C]-rigosertib | Experimental | Drug: rigosertibA 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rigosertibAlso: rigosertib sodium, ON 01910.NaA 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 | [14C]-rigosertib |
Primary outcome
The mean percent of the radioactivity of the administered doses recovered in the urine, feces, and overall (urine + feces)
Time frame: Up to 216 hours
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.
Concentration of rigosertib in plasma
Time frame: Up to 216 hours
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.
Concentration of radioactivity in whole blood
Time frame: Up to 216 hours
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.
Concentration of radioactivity in plasma
Time frame: Up to 216 hour
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.
5 secondary outcomes
Metabolite profiling
Time frame: Up to 216 hours
Metabolite identification
Time frame: Up to 216 hours
Concentration of radioactivity in urine
Time frame: Up to 216 hours
Concentration of radioactivity in feces
Time frame: Up to 216 hours
Number of subjects who experience an adverse event
Time frame: Up to 31 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2017.
- Results publicationGarcia-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois Wilhelm, MD, PhD study chair
Traws Pharma, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rigosertib in people with Healthy, run by Traws Pharma, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean percent of the radioactivity of the administered doses recovered in the urine, feces, and overall (urine + feces) (time frame: Up to 216 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02030639, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2017.