Phase 1
Completed N=55
Safety, Tolerability and Pharmacokinetic (PK) of Concomitant Esomeprazole and Rifampin, and QT Study on Single and Multiple-doses of Alisertib
Source: ClinicalTrials.gov NCT01844583 ↗Enrolled (actual)
55
Serious AEs
36.4%
Results posted
Mar 2019
Primary outcomePrimary: Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole — 1542.6; 1804.8 nmol/L
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole |
1542.6; 1804.8 | — |
| PRIMARY 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 |
20427.8; 25094.4 | — |
| PRIMARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole |
21371.4; 26612.5 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole |
4.0; 3.0 | — |
| PRIMARY Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole |
16.06; 15.96 | — |
| PRIMARY Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin |
1561.4; 1581.5 | — |
| PRIMARY 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 |
19732.0; 9470.5 | — |
| PRIMARY AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin |
17258.3; 8955.0 | — |
| PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin |
4.0; 2.1 | — |
| PRIMARY Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin |
16.30; 8.17 | — |
| PRIMARY Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) |
-2.2; -3.7; -5.4; -4.5; -3.5; -4.0 | — |
| SECONDARY Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) |
-2.4; -3.9; -5.3; -4.6; -3.9; -3.5 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
25; 27; 9; 11 | — |
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
Please note there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Data sourced from ClinicalTrials.gov (NCT01844583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.