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Aims: Cladribine tablets have shown significant efficacy for the treatment of relapsing multiple sclerosis, a chronic and debilitating immune‐mediated disorder. This study was conducted to examine acute and/or cumulative effects of cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dose over 2 years) on heart rate, AV conduction and cardiac repolarization in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: CLARITY was a 96‐week, double‐blind, placebo‐controlled, multicentre trial which evaluated the safety and efficacy of cladribine tablets 3.5 and 5.25 mg/kg body weight in patients with RRMS. A total of 135 patients were included in the ECG substudy, providing a total of 1534 post‐dose ECGs. ECG data were collected 15 minutes pre‐dose and between 0.5 and 3 hours post‐dose at pre‐study evaluation, study Day 1 and Weeks 5, 9, 13, 48 and 52. Results: For cladribine tablets 3.5 mg/kg, the maximum change in placebo‐adjusted post‐dose QTcF vs. visit‐baseline (BL) was −0.42 ms (90% CI: −3.61–4.44) at Week 1 (acute effects), and 3.20 ms (90% CI: −0.08–6.33) for cladribine tablets 5.25 mg/kg. The greatest observed differences in post‐dose QTcF vs. study BL occurred at Week 48 for both the 3.5 and 5.25 mg/kg doses of cladribine tablets with 5.99 ms (90% CI: 0.53–11.44) and 8.74 ms (90% CI: 3.18–14.31), respectively. No significant changes were observed in T‐wave morphology in either treatment group. Conclusions: Cladribine tablets 3.5 mg/kg (approved dose in Europe/other regions) did not confer clinically meaningful effects on heart rate, AV conduction and ventricular repolarization. [ABSTRACT FROM AUTHOR]

The article discusses the importance of electrocardiogram (ECG) reading on clinical research and practice. It stresses that it is critical in data collection during clinical research with the investigational drug's cardiac safety profile, especially the interval duration measurements of heart activity, emphasizing ECG centralization. It suggests that relevance of the findings should also be associated with one's prior history and current health status.

The article discusses the implication of electrocardiography (ECG) in the development of drugs as well as the use of laboratories. According to the article, ECGs are used to gather information as well as assess the effect of investigational drugs on the electrical functions of the heart. In addition, it states that sponsors should consider several factors such as reducing the price they pay for research since it does not give them the assurance that all the results are correct. INSET: Homework for Sponsors.

This study investigated the effect of eslicarbazepine acetate (ESL) on cardiac repolarization in healthy adult volunteers. A randomized, placebo/active-controlled, 4-period crossover study was conducted in 67 participants. In 3 periods, participants received once-daily doses of ESL 1200 mg, ESL 2400 mg, and placebo for 5 days; in 1 period, participants received placebo on days 1 to 4 and a 400-mg moxifloxacin single dose on day 5. In each period, 24-hour 12-lead Holter monitoring was performed on days –1 (baseline) and 5. There was no clinically relevant effect of ESL 1200 mg and 2400 mg versus placebo on cardiac depolarization or repolarization as measured by the QRS or QTc intervals, respectively. Mean PR interval increased following ESL 1200 mg and 2400 mg, but there was no participant with a PR interval above the upper limit of the normal range (200 ms). The upper bound of the 95% confidence interval for the placebo-corrected change from baseline of the individually corrected QT interval (QTcI) following administration of ESL 1200 mg and ESL 2400 mg was <10 ms at every time point. Moxifloxacin caused an increase in QTcI above the 10-ms threshold for clinical significance at several time points, demonstrating assay sensitivity. It is concluded that administration of ESL 1200 mg and ESL 2400 mg did not induce a clinically significant prolongation of the QTcI interval. [ABSTRACT FROM PUBLISHER]

The article discusses the scientific approach in the centralization of electrocardiogram (ECG) Phase III on cardiac safety risk assessment. It emphasizes the QT wave interval prolongation, or the contraction and repolarization of cardiac muscles, on polymorphic ventricular tachycardia or torsades de pointes during drug interaction. The clinical trial "Thorough QT/QTc (TQT) Study" promotes cardiac safety data collection associated with market drugs and further enhances assessment.

The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebocontrolled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc intervals was <10 ms for all 4 correction methods. Moxifloxacin (400 mg) increased QTc intervals by 10.6 to 12.3 ms at 2 hours. There was no concentration-exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases >60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the QTc interval. [ABSTRACT FROM AUTHOR]