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Trial record 30 of 59 for:    MLN8237

Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib

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ClinicalTrials.gov Identifier: NCT01714947
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : October 31, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE October 17, 2012
First Posted Date  ICMJE October 26, 2012
Results First Submitted Date  ICMJE February 20, 2018
Results First Posted Date  ICMJE October 31, 2018
Last Update Posted Date October 31, 2018
Actual Study Start Date  ICMJE January 24, 2013
Actual Primary Completion Date April 4, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
  • Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞ [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞ [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ae: Amount of [^14C]-Alisertib Excreted in Urine [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ae: Amount of [^14C]-Alisertib Excreted in Feces [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Percent of Total Radioactivity (TRA) in Urine and Feces [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Fe: Fraction of Administered Dose of Alisertib Excreted in Urine [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Ae: Amount of Alisertib Excretion in Urine [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
  • Renal Clearance (CLR) of Alisertib [ Time Frame: Predose and multiple timepoints post-dose (up to 240 hours) ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2012)
  • Time to maximum plasma concentration [ Time Frame: Daily for approximately 10 days ]
    Pharmacokinetics of alisertib in plasma and total radioactivity in plasma and whole blood
  • Percent urinary recovery [ Time Frame: Daily for approximately 10 days ]
  • Alisertib excretion in urine [ Time Frame: Daily for approximately 10 days ]
  • Percent fecal excretion [ Time Frame: Daily for approximately 10 days ]
  • Percent of total radioactivity in urine and feces [ Time Frame: Daily for approximately 10 days ]
Change History Complete list of historical versions of study NCT01714947 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
  • Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (0 to 192 hours) ]
    Total radioactive peak distributions of metabolites in 0 to 192 hours pooled plasma samples from participants.
  • Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (0 to 192 hours) ]
    Total radioactive peak distributions of metabolites in 0 to 192 hours pooled urine samples from participants.
  • Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution [ Time Frame: Predose and multiple timepoints post-dose (0 to 192 hours) ]
    Total radioactive peak distributions of metabolites in 0 to 192 hours pooled fecal samples from participants.
  • Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events [ Time Frame: From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days) ]
    An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) was defined as any AE at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity or resulted in congenital anomaly/birth defect. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
  • Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs [ Time Frame: Part A: Day 1 and End of Study (EOS) Day 31 if not continuing to Part B, Part B: Days 8 and 15 of each cycle and EOS (Up to 117 days) ]
    An abnormal laboratory was assessed to be an AE if the value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline.
  • Number of Participants With Clinically Significant Changes or Abnormalities in Vital Sign Measurements [ Time Frame: Part A: Day 1 and EOS (Day 31 if not continuing to Part B), Part B: Day 1 of each cycle and EOS (Up to 117 days) ]
    Vital signs included body temperature, heart rate, and sitting blood pressure. The investigator determined if the changes were clinically significant.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2012)
  • Amount of metabolites in plasma [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles
  • Number of adverse events [ Time Frame: From first dose of study drug through 30 days after the last dose of study drug ]
    Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, and vital sign measurements
  • Amount of metabolites in urine [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles
  • Amount of metabolites in feces [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib
Official Title  ICMJE Mass Balance, Pharmacokinetics, and Metabolism of [^14C]-Alisertib in Patients With Advanced Solid Tumors or Lymphomas
Brief Summary The purpose of this study is to assess the mass balance (i.e. cumulative excretion of total radioactivity [TRA] in urine and feces) of alisertib and pharmacokinetic (PK) of alisertib in plasma and urine, and of TRA in plasma and whole blood.
Detailed Description

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat participants who have advanced solid tumors or lymphomas. This study looked at mass balance, pharmacokinetics (PK), metabolism, elimination and safety of alisertib.

The study enrolled 3 patients. The study consisted of 2 parts: Part A and Part B. Participants received:

  • [^14C]-alisertib 35 mg in Part A
  • alisertib 50 mg in Part B

Participants were asked to take a single dose of [^14C]-alisertib oral solution containing 80-100 μCi of total radioactivity (1.19-1.48 mCi/mmol) in Part A and alisertib 50 mg, orally, twice daily for 7 days in 21-day cycles until disease progression or unacceptable toxicity in Part B.

This single center trial was conducted in United States. The overall time to participate in this study was up to 117 days. Participants remained confined to clinic in Part A and made multiple visits to the clinic in Part B. Participants were contacted 30 days after last dose of alisertib in Part A (if not continuing in Part B), or were contacted by telephone or a final visit 30 days after receiving their last dose of alisertib in Part B for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Lymphoma
Intervention  ICMJE
  • Drug: [^14C]-alisertib
    [^14C]-alisertib oral solution
    Other Name: MLN8237
  • Drug: alisertib
    Alisertib enteric coated tablets
    Other Name: MLN8237
Study Arms  ICMJE Experimental: Alisertib

Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1.

Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).

Interventions:
  • Drug: [^14C]-alisertib
  • Drug: alisertib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 30, 2013)
3
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2012)
6
Actual Study Completion Date  ICMJE June 14, 2013
Actual Primary Completion Date April 4, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Each participants must meet all of the following inclusion criteria to be enrolled in the study:

  • 18 years or older.
  • Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment does not exist, or is no longer effective or tolerable.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Expected survival longer than 3 months from enrollment in the study.
  • Radiographically or clinically evaluable tumor.
  • Suitable venous access for the conduct of blood sampling.
  • Recovered from the reversible effects of prior antineoplastic treatment (with the exception of alopecia and Grade 1 neuropathy).
  • Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time.
  • Male participants who agree to practice effective barrier contraception during the entire study and through 4 months after the last dose of study drug OR agree to abstain from heterosexual intercourse.

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Female participants who are lactating or have a positive serum pregnancy test.
  • Treatment with any investigational products or systemic antineoplastic treatment within 21 days before the first dose of alisertib.
  • Medical conditions requiring daily, chronic, or regular use of proton pump inhibitors(PPIs) within 7 days preceding the first dose of alisertib, or H2-receptor antagonists within 24 hours preceding the first dose of alisertib.
  • Participants requiring systemic anticoagulation (excluding low-dose aspirin, or low-dose anticoagulation to maintain patency of venous access devices). Low molecular weight heparin, administered as preventive treatment, is allowed if the participant has tolerated treatment with a stable dose and schedule without bleeding complications for more than 1 month.
  • Major surgery within the 14 days preceding the first dose of alisertib.
  • Infection requiring systemic intravenous (IV) antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
  • Life-threatening or uncontrolled medical illness unrelated to cancer.
  • Ongoing nausea or vomiting that is Grade 2 or worse in intensity.
  • Diarrhea that is Grade 2 or worse in intensity or use of an antimotility agent to control diarrhea to an intensity of Grade 1 or lower level.
  • Known GI disease or GI procedures that could interfere with the oral absorption, excretion, or tolerance of alisertib.
  • History of urinary and/or fecal incontinence.
  • History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease.
  • Inability to swallow tablets, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after the first dose of alisertib.
  • Inadequate bone marrow or other organ function as specified in study protocol.
  • Any cardiovascular condition specified in the study protocol.
  • Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
  • Inability to comply with study visits and procedures including required inpatient confinement (approximately 11-17 days).

Please note that there are additional exclusion criteria. The study center will determine if you meet all of the criteria.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01714947
Other Study ID Numbers  ICMJE C14014
U1111-1187-6760 ( Other Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Clinical Science Takeda
PRS Account Takeda
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP