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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alisertib

Esomeprazole

Rifampin

About this trial

This is an interventional treatment trial for Solid Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Esomeprazole 40 mg + Alisertib 50 mg

Rifampin 600 mg + Alisertib 50 mg

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcome Measures

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

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

An Adverse Event (AE) is 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) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Full Information

NCT ID

NCT01844583

First Posted

April 29, 2013

Last Updated

December 18, 2018

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01844583

Brief Title

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

Official Title

Study of the Effect of Esomeprazole or Rifampin on the Pharmacokinetics of Alisertib and Evaluation of the Effect of Alisertib on the QTc Interval in Patients With Advanced Solid Tumors or Lymphomas

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

June 25, 2013 (Actual)

Primary Completion Date

August 4, 2014 (Actual)

Study Completion Date

September 6, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumors, Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

55 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Esomeprazole 40 mg + Alisertib 50 mg

Arm Type

Experimental

Arm Description

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).

Arm Title

Rifampin 600 mg + Alisertib 50 mg

Arm Type

Experimental

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

Alisertib

Other Intervention Name(s)

MLN8237

Intervention Description

Alisertib tablets

Intervention Type

Drug

Intervention Name(s)

Esomeprazole

Intervention Description

Esomeprazole capsules

Intervention Type

Drug

Intervention Name(s)

Rifampin

Intervention Description

Rifampin capsules

Primary Outcome Measure Information:

Title

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

Time Frame