A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of Veliparib (ABT-888) on Cardiac Repolarization in Subjects with Relapsed or Refractory Solid Tumors

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

- Confirmed solid malignancy that is metastatic or unresectable for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective.
- Subjects with brain metastases must have clinically controlled neurologic sysptoms.
- Subject is able to swallow and retain oral medications and does not have uncontrolled emesis.
- Subject has adequate bone marrow, renal and hepatic function per local laboratory reference ranges.
- Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or
study-specific procedures.

Exclusion Criteria

- Subject has a screening or baseline (pre-dose on Day 1 of Period 1 at approximately 8 - 10 AM) corrected QT interval (QTc) interval by Fridericia's correction (QTcF) > 470 ms.
- Uncorrected serum potassium, serum magnesium, serum calcium or free thyroxine (FT4) and thyroid stimulating hormone (TSH) outside of normal reference ranges, or grade 2 hyponatremia or hypernatremia.
- Subject has severe ECG morphologic abnormalities that make QTc evaluation difficult.
- Subject has a history of cardiac conduction abnormalities including:
• PR interval > 220 ms or < 115 ms;
• evidence of second or third degree atrioventricular (AV) block;
• evidence of ventricular pre-excitation;
• intraventricular conduction delay with QRS duration > 136 ms;
• bradycardia as defined by sinus rate < 47 bpm.
- Subject has a significant history of cardiovascular disease including congenital long-QT syndrome, angina, myocardial ischemia or infarction, thrombotic or thromboembolic event in the last 6 months, myocarditis, angina on exertion, uncorrected hypocalcemia (<= 8.2 mg/dL), idiopathic cardiomyopathy, amyloid, tumor, sarcoid, scleroderma, syncope, epilepsy, hypertonic cardiomyopathy, or other clinically significant cardiac disease or baseline ECG abnormalities that could potentially confound subsequent analyses.
- Subject has received any anti-cancer therapies 21 days prior to the first dose of study drug, or has recovered to no better than a grade 2 or higher clinically significant adverse effect(s)/toxicity(s) of the previous therapy.
- Use of drugs with a known risk for QT prolongation and Torsades de Pointes within 7 days prior to the first study dose.
- Use of tobacco or nicotine-containing products within 12 hours prior to the first study dose.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to evaluate the effect of veliparib on<br /><br>QTcF. Evaluation of this point will be done once 36 subjects have completed all<br /><br>3 dosing periods. </p><br>

Secondary Outcome Measures