Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib

NCT01714947 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C14014U1111-1187-6760
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors; Lymphoma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (20)

• Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution

  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

  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

  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

  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

  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

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞

  Predose and multiple timepoints post-dose (up to 240 hours)

• Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine

  Predose and multiple timepoints post-dose (up to 240 hours)

• Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ae: Amount of [^14C]-Alisertib Excreted in Urine

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ae: Amount of [^14C]-Alisertib Excreted in Feces

  Predose and multiple timepoints post-dose (up to 240 hours)

• Percent of Total Radioactivity (TRA) in Urine and Feces

  Predose and multiple timepoints post-dose (up to 240 hours)

• Fe: Fraction of Administered Dose of Alisertib Excreted in Urine

  Predose and multiple timepoints post-dose (up to 240 hours)

• Ae: Amount of Alisertib Excretion in Urine

  Predose and multiple timepoints post-dose (up to 240 hours)

• Renal Clearance (CLR) of Alisertib

  Predose and multiple timepoints post-dose (up to 240 hours)

Secondary Outcomes (6)

• Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution

  Predose and multiple timepoints post-dose (0 to 192 hours)

• Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution

  Predose and multiple timepoints post-dose (0 to 192 hours)

• Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution

  Predose and multiple timepoints post-dose (0 to 192 hours)

• Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events

  From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)

• Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs

  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)

Study Arms (1)

Alisertib

EXPERIMENTAL

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).

Drug: [^14C]-alisertib; Drug: alisertib

Interventions

[^14C]-alisertib DRUG

\[\^14C\]-alisertib oral solution

Also known as: MLN8237

Alisertib

alisertib DRUG

Alisertib enteric coated tablets

Also known as: MLN8237

Alisertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Comprehensive Clinical Development

Tacoma, Washington, 98418, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 26, 2012
• Study Start: January 24, 2013
• Primary Completion: April 4, 2013
• Study Completion: June 14, 2013
• Last Updated: October 31, 2018
• Results First Posted: October 31, 2018

Record last verified: 2018-02

Locations

US (1)