Safety, Tolerability and Pharmacokinetic (PK) of Concomitant Esomeprazole and Rifampin, and QT Study on Single and Multiple-doses of Alisertib

NCT ID: NCT01844583

Last Updated: 2019-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-25
• Study Completion Date: 2016-09-06

Brief Summary

The purpose of this study is to assess the drug-drug interaction (DDI) of either esomeprazole or rifampin on the single-dose PK of alisertib, and to complete an intensive QT study of single and multiple-dose alisertib.

Detailed Description

The drug tested in this study is called alisertib. Alisertib is being tested to assess the effect of a proton pump inhibitor and strong metabolic inducer on the PK of a single 50 mg dose of alisertib administered as enteric-coated tablets (ECTs).

The study enrolled 55 patients. Participants received either:

• Esomeprazole 40 mg and Alisertib 50 mg
• Rifampin 600 mg and Alisertib 50 mg

All participants were asked to take one tablet of alisertib either once or twice daily in all cycles. In Cycle 2, participants were asked to take alisertib plus either esomeprazole or rifampin.

This trial was conducted the United States. The overall time to participate in this study was 10 months. Participants made multiple visits to the clinic plus a final visit, 30 days after receiving their last dose of study drug for a follow-up assessment.

Conditions

Solid Tumors; Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Esomeprazole 40 mg + Alisertib 50 mg

Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.

Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2.

Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib tablets

Esomeprazole

Intervention Type: DRUG

Esomeprazole capsules

Rifampin 600 mg + Alisertib 50 mg

Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1.

Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2.

Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib tablets

Rifampin

Intervention Type: DRUG

Rifampin capsules

Interventions

Alisertib

Alisertib tablets

Intervention Type: DRUG

Esomeprazole

Esomeprazole capsules

Intervention Type: DRUG

Rifampin

Rifampin capsules

Intervention Type: DRUG

Other Intervention Names

MLN8237

Eligibility Criteria

Inclusion Criteria

• Male or female participants 18 years or older
• Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Expected survival longer than 3 months from enrollment in the study
• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse

Exclusion Criteria

• Treatment with any anticancer therapy or any investigational agents within 4 weeks before the first dose of alisertib

• Known hypersensitivity or intolerance to rifampin (for participants considered for the rifampin drug-drug interaction [DDI] group) or to esomeprazole (for participants considered for the esomeprazole DDI group)
• Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib, and known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib
• Participants requiring treatment with clinically significant enzyme inducers within 14 days before the first dose of alisertib and/or requiring the use of these medications during the study
• A medical condition requiring use of pancreatic enzymes; or daily, chronic, or regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists
• Participants requiring systemic anticoagulation (excluding low-dose aspirin, or low-dose anticoagulation to maintain patency of venous access devices).
• Any cardiovascular condition
• Female participants who are lactating or have a positive serum pregnancy test
• Major surgery within the 14 days preceding the first dose of alisertib

• Life-threatening or uncontrolled medical illness unrelated to cancer
• Newly diagnosed or uncontrolled cancer-related central nervous system (CNS) disease
• Autologous stem cell transplant within 3 months
• Prior allogeneic bone marrow or other organ transplantation

• Other severe acute or chronic medical or psychiatric condition
• Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Sarasota, Florida, United States

St Louis, Missouri, United States

Oklahoma City, Oklahoma, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

San Antonio, Texas, United States

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

C14015

Identifier Type: -

Identifier Source: org_study_id