Lack of Significant Effect of Bilastine Administered at Therapeutic and Supratherapeutic Doses and Concomitantly With Ketoconazole on Ventricular Repolarization: Results of a Thorough QT Study (TQTS) With QT‐Concentration Analysis

  title={Lack of Significant Effect of Bilastine Administered at Therapeutic and Supratherapeutic Doses and Concomitantly With Ketoconazole on Ventricular Repolarization: Results of a Thorough QT Study (TQTS) With QT‐Concentration Analysis},
  author={Beno{\^i}t Tyl and Meriam Kabbaj and Sara Azzam and Ander Sologuren and Rom{\'a}n Valiente and Elizabeth Reinbolt and Kathryn Ann Roupe and Nathalie Blanco and William Wheeler},
  journal={The Journal of Clinical Pharmacology},
The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple‐dose, triple‐dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time‐matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16… 

Effects of Bilastine on T-wave Morphology and the QTc Interval

Bilastine, at therapeutic and supratherapeutic dosages, does not induce any effects on T-wave morphology or QTcF, and results confirm the absence of an effect for bilastine on cardiac repolarization.

Evaluation of the Single-dose Pharmacokinetics of Bilastine in Subjects with Various Degrees of Renal Insufficiency

Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Bioequivalence Evaluation of Three Pediatric Oral Formulations of Bilastine in Healthy Subjects: Results from a Randomized, Open Label, Crossover Study

Bilastine was well tolerated when administered indistinctly as an orodispersible tablet or as an oral solution and was bioequivalent to the reference formulation.

Safety profile of bilastine: 2nd generation H1-antihistamines.

  • F. Scaglione
  • Medicine, Biology
    European review for medical and pharmacological sciences
  • 2012
Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism, and it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

PKPD and cardiac single cell modeling of a DDI study with a CYP3A4 substrate and itraconazole to quantify the effects on QT interval duration

The C-QT model for basmisanil can be used to derive the QT interval corrected changes in heart rate (QTc) and thus inform cardiac safety strategy in later development without the need for a separate, dedicated study.

Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors

The results demonstrate lack of effect of necitumumab on the QTc interval in heavily pretreated patients with advanced solid tumors, suggesting that QT prolongation is not a major safety concern for necitUMumab at the recommended therapeutic dose.

Safety and efficacy of bilastine: a new H1-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria

  • M. Church
  • Medicine
    Expert opinion on drug safety
  • 2011
Bilastine has high selectivity for H1-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood–brain barrier.

Ef fi cacy and safety of bilastine in Japanese patients with perennial allergic rhinitis : A multicenter , randomized , double-blind , placebo-controlled , parallel-group phase III study

After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.



Co-administration of ketoconazole with H1-antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects.

Ketoconazole altered the pharmacokinetic profiles of both ebastine and loratadine although the effect was greater for the former drug, and changes in uncorrected QT intervals for both antihistamines were not statistically different from those observed with ketoconazoles alone.

Comparison of Peripheral and Central Effects of Single and Repeated Oral Dose Administrations of Bilastine, a New H1 Antihistamine: A Dose-Range Study in Healthy Volunteers With Hydroxyzine and Placebo as Control Treatments

A clear dissociation between peripheral anti-H1 and central nervous system activity was found after BIL treatment and significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL.

Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study

Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic and supra-therapeutic doses on cardiac repolarisation.

Raltegravir Thorough QT/QTc Study: A Single Supratherapeutic Dose of Raltegravir Does Not Prolong the QTcF Interval

A single supratherapeutic dose design may be appropriate for crossover thorough QTc studies, after a double‐blind, randomized, placebo‐controlled, double‐dummy, 3‐period, single‐dose crossover study conducted.

Ketoconazole and Rifampin Significantly Affect the Pharmacokinetics, But Not the Safety or QTc Interval, of Casopitant, a Neurokinin‐1 Receptor Antagonist

Three phase 1 studies with 131 healthy subjects confirmed the role of CYP3A in the metabolism and disposition of casopitant and suggested coadministration with strong inducers of CYp3A is likely to decrease casopant exposure and compromise efficacy.

Pharmacokinetics and Pharmacodynamics of Three Moxifloxacin Dosage Forms: Implications for Blinding in Active‐Controlled Cardiac Repolarization Studies

Over‐encapsulation of moxifloxacin did not alter its peak or total systemic exposures or pharmacodynamics after oral a dministration, and changes in QTcF mirrored the pharmacokinetic changes, and there was a linear relationship between plasma concentration of mxifl oxacin and change in QtcF.

Choice of baseline in a multiple-dose thorough QT study (TQTS) – effect on analysis of moxifloxacin-induced QTc prolongation

The collection of ECG tracings during a full baseline day before each period was associated with the lowest variability, however, the two more cost effective designs were sufficient, in this small TQTS, to significantly detect moxifloxacin.

The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber

Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study and had a rapid onset of action within 1 h, and a long duration of action, greater than 26 h.

Effect of Number of Replicate Electrocardiograms Recorded at Each Time Point in a Thorough QT Study on Sample Size and Study Cost

To determine the most cost‐effective number of ECG replicates, the authors retrospectively analyzed data from the placebo and moxifloxacin arms of a TQT study with crossover design to find the study cost was least with 3 or 4 replicates.

Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi‐centre, double‐blind, randomized, placebo‐controlled study

To cite this article: Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, Antépara I, Jáuregui I, Valiente R, the Bilastine International Working Group. Comparison of the efficacy and safety