Sabiha A Mondal1, Mahmoud Assaf2, Liangang Liu2, Edward O'Mara3. 1. PPD Phase 1 Clinic, Austin, TX, USA. 2. Celgene Corporation, 86 Morris Avenue, Summit, NJ, 07901, USA. 3. Celgene Corporation, 86 Morris Avenue, Summit, NJ, 07901, USA. omara_edward@yahoo.com.
Abstract
PURPOSE:Pomalidomide is a distinct immunomodulatory agent approved for the treatment of relapsed and refractory multiple myeloma. QT interval was monitored in prior studies, and although there was no indication that pomalidomide could induce QT prolongation, a formal analysis was not previously conducted. Therefore, we present here the results of a study evaluating the effects of pomalidomide on QT interval corrected for heart rate (QTc) using Fridericia's formula (QTcF) and other electrocardiogram (ECG) parameters. METHODS:Healthy male volunteers with normal or clinically acceptable laboratory tests and ECG results were randomized to receive single oral doses of placebo, pomalidomide 4 mg, pomalidomide 20 mg, and moxifloxacin 400 mg (positive control) in different sequences. Subjects were evaluated by digital ECG monitoring and underwent blood sampling and standard safety monitoring. RESULTS:Seventy-two subjects were enrolled. In ECG evaluations performed after dosing with pomalidomide 4 mg (therapeutic dose) or 20 mg (supratherapeutic dose), the upper limit of the two-sided 90 % CI for mean change from baseline and placebo-corrected QTcF was <10 ms at all postdose time points, which is below the defined threshold of regulatory concern. In contrast, moxifloxacin induced a clear prolongation in QT interval. Changes in heart rate and other ECG parameters after pomalidomide dosing were clinically insignificant. CONCLUSIONS:Pomalidomide given as a single oral dose of up to 20 mg was not associated with QT prolongation in healthy male subjects.
RCT Entities:
PURPOSE:Pomalidomide is a distinct immunomodulatory agent approved for the treatment of relapsed and refractory multiple myeloma. QT interval was monitored in prior studies, and although there was no indication that pomalidomide could induce QT prolongation, a formal analysis was not previously conducted. Therefore, we present here the results of a study evaluating the effects of pomalidomide on QT interval corrected for heart rate (QTc) using Fridericia's formula (QTcF) and other electrocardiogram (ECG) parameters. METHODS: Healthy male volunteers with normal or clinically acceptable laboratory tests and ECG results were randomized to receive single oral doses of placebo, pomalidomide 4 mg, pomalidomide 20 mg, and moxifloxacin 400 mg (positive control) in different sequences. Subjects were evaluated by digital ECG monitoring and underwent blood sampling and standard safety monitoring. RESULTS: Seventy-two subjects were enrolled. In ECG evaluations performed after dosing with pomalidomide 4 mg (therapeutic dose) or 20 mg (supratherapeutic dose), the upper limit of the two-sided 90 % CI for mean change from baseline and placebo-corrected QTcF was <10 ms at all postdose time points, which is below the defined threshold of regulatory concern. In contrast, moxifloxacin induced a clear prolongation in QT interval. Changes in heart rate and other ECG parameters after pomalidomide dosing were clinically insignificant. CONCLUSIONS:Pomalidomide given as a single oral dose of up to 20 mg was not associated with QT prolongation in healthy male subjects.
Authors: Igor Radanovic; Naomi Klarenbeek; Robert Rissmann; Geert Jan Groeneveld; Emilie M J van Brummelen; Matthijs Moerland; Jacobus J Bosch Journal: Front Oncol Date: 2022-08-29 Impact factor: 5.738