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

NCT01844583 | Completed Phase 1 Results

• 1 other identifier: C14015
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 7

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.

Conditions

Solid Tumors; Lymphoma

Outcome Measures

Primary Outcomes (11)

• Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm

• AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm

• Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm

• Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm

• AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm

• Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm

• Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI)

  Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1

Secondary Outcomes (2)

• Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF)

  Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)

Study Arms (2)

Esomeprazole 40 mg + Alisertib 50 mg

EXPERIMENTAL

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).

Drug: Alisertib; Drug: Esomeprazole

Rifampin 600 mg + Alisertib 50 mg

EXPERIMENTAL

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).

Drug: Alisertib; Drug: Rifampin

Interventions

Alisertib DRUG

Alisertib tablets

Also known as: MLN8237

Esomeprazole 40 mg + Alisertib 50 mg; Rifampin 600 mg + Alisertib 50 mg

Esomeprazole DRUG

Esomeprazole capsules

Esomeprazole 40 mg + Alisertib 50 mg

Rifampin DRUG

Rifampin capsules

Rifampin 600 mg + Alisertib 50 mg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

Unknown Facility

Sarasota, Florida, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Madison, Wisconsin, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

MLN 8237; Esomeprazole; Rifampin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: June 25, 2013
• Primary Completion: August 4, 2014
• Study Completion: September 6, 2016
• Last Updated: March 25, 2019
• Results First Posted: March 25, 2019

Record last verified: 2018-12

Locations

US (7)