0744 Cardiac Safety Profile of Pitolisant in Patients with Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A283-A283
Author(s):  
W Winter ◽  
S P Wanaski ◽  
A Patroneva ◽  
J M Dayno
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pooled Analysis ◽  
Mean Difference ◽  
Qtc Interval ◽  
Cardiac Safety ◽  
Open Label ◽  
Long Term Study ◽  
End Of Treatment

Abstract Introduction Cardiovascular diseases are comorbid in patients with narcolepsy. Cardiovascular adverse effects are of concern with narcolepsy medications because of this comorbidity and most patients require lifelong pharmacotherapy. Pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist, increases histamine transmission in the brain. In a QT study of healthy volunteers, pitolisant (35.6 mg/day) led to a mean increase of 4.2 msec in QTc interval. This analysis further characterized the cardiac safety of pitolisant (maximum dose, 35.6 mg/day) in adults with narcolepsy. Methods Data were obtained from a pooled analysis of 2 randomized, placebo-controlled, 7- or 8-week studies and from a 12-month, open-label study. Results Pooled analysis included 166 patients (pitolisant, n=85; placebo, n=81). Mean change in heart rate from baseline to end-of-treatment was -0.5 beats/min with pitolisant and -0.2 beats/min with placebo (LS mean difference, -0.4; P=0.744). Mean change was also similar for pitolisant versus placebo in systolic (LS mean difference, 0.0; P=0.983) and diastolic (LS mean difference, -0.6; P=0.552) blood pressure, as was mean change in QTc interval (LS mean difference, 0.4; P=0.911). Cardiac adverse events with pitolisant included heart rate increase (n=4), right bundle branch block (n=1), sinus tachycardia (n=1), and palpitations (n=1), and with placebo included blood pressure increase (n=1). In the long-term study, mean change from baseline in QTc interval was 3.1 msec at Month 6 (n=70) and 6.1 msec at Month 12 (n=67); 3 patients had a postbaseline increase >60 msec but none had QTc >500 msec. Conclusion In this analysis, no cardiac safety signals were observed during treatment with pitolisant administered up to the maximum recommended dose. Because concomitant use of pitolisant with other drugs known to increase the QT interval may add to the QT effects of pitolisant, avoid use of pitolisant in combination with these medications. Support Bioprojet Pharma and Harmony Biosciences, LLC.

Carteolol Treatment of Essential Hypertension: A Long-Term Study of Safety and Efficacy

1986 ◽  
Vol 14 (4) ◽  
pp. 175-184 ◽  
Author(s):  
Robert R Luther ◽  
Clemeth J Maurath ◽  
Michael J Klepper ◽  
Robert O Peckinpaugh ◽  
Gary L Ringham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multicenter Trial ◽  
Open Label ◽  
Once Daily ◽  
Long Term Study ◽  
Daily Dose ◽  
Baseline Values ◽  
The Mean ◽  
Oral Doses

The long-term safety and antihypertensive efficacy of carteolol were evaluated in an open-label, multicenter trial of 245 hypertensive patients. For those patients maintained on carteolol monotherapy, three months of treatment with once-daily oral doses of carteolol ranging from 2.5 to 60 mg reduced the mean recumbent blood pressure by 12/14 mm Hg from baseline values of 151/100. Blood pressure reductions observed at three months were maintained throughout the study. The final daily dose of carteolol for most patients was 10 mg or less. Carteolol was shown to be safe and well tolerated by most patients.

scholarly journals Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 164-165
Author(s):  
Samuel Frank ◽  
Claudia M. Testa ◽  
David Stamler ◽  
Elise Kayson ◽  
David Oakes ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Study Drug ◽  
Motor Dysfunction ◽  
Open Label ◽  
Entire Treatment Period ◽  
End Of Treatment ◽  
Pharmaceutical Industries

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Age dependence of brachial cuff-based ambulatory PWV in end-stage kidney disease patients undergoing long-term peritoneal dialysis

2021 ◽  
pp. 089686082199692
Author(s):  
Vasilios Vaios ◽  
Panagiotis I Georgianos ◽  
Georgia Vareta ◽  
Dimitrios Divanis ◽  
Evangelia Dounousi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Heart Rate ◽  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Pulse Wave ◽  
Age Dependence ◽  
End Stage Kidney Disease ◽  
End Stage

Background: The newly introduced device Mobil-O-Graph (IEM, Stolberg, Germany) combines brachial cuff oscillometry and pulse wave analysis, enabling the determination of pulse wave velocity (PWV) via complex mathematic algorithms during 24-h ambulatory blood pressure monitoring (ABPM). However, the determinants of oscillometric PWV in the end-stage kidney disease (ESKD) population remain poorly understood. Methods: In this study, 81 ESKD patients undergoing long-term peritoneal dialysis underwent 24-h ABPM with the Mobil-O-Graph device. The association of 24-h oscillometric PWV with several demographic, clinical and haemodynamic parameters was explored using linear regression analysis. Results: In univariate analysis, among 21 risk factors, 24-h PWV exhibited a positive relationship with age, body mass index, overhydration assessed via bioimpedance spectroscopy, diabetic status, history of dyslipidaemia and coronary heart disease, and it had a negative relationship with female sex and 24-h heart rate. In stepwise multivariate analysis, age ( β: 0.883), 24-h systolic blood pressure (BP) ( β: 0.217) and 24-h heart rate ( β: −0.083) were the only three factors that remained as independent determinants of 24-h PWV (adjusted R 2 = 0.929). These associations were not modified when all 21 risk factors were analysed conjointly or when the model included only variables shown to be significant in univariate comparisons. Conclusion: The present study shows that age together with simultaneously assessed oscillometric BP and heart rate are the major determinants of Mobil-O-Graph-derived PWV, explaining >90% of the total variation of this marker. This age dependence of oscillometric PWV limits the validity of this marker to detect the premature vascular ageing, a unique characteristic of vascular remodelling in ESKD.

ABPM Comparison of the Anti-Hypertensive Profiles of Telmisartan and Enalapril in Patients with Mild-to-Moderate Essential Hypertension

2002 ◽  
Vol 30 (6) ◽  
pp. 543-552 ◽  
Author(s):  
J Amerena ◽  
S Pappas ◽  
J-P Ouellet ◽  
L Williams ◽  
D O'Shaughnessy
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Blood Pressure Monitoring ◽  
Study Drug ◽  
Pressure Control ◽  
Moderate Essential Hypertension ◽  
Open Label ◽  
Night Time ◽  
Once Daily

In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40–80 mg and enalapril 10–20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was ≥ 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of −2.02 mmHg ( P < 0.01). A significantly greater proportion of patients achieved a seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05), also measured with the same ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.

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