scholarly journals Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency

2014 ◽  
Vol 171 (3) ◽  
pp. 369-377 ◽  
Author(s):  
A G Nilsson ◽  
C Marelli ◽  
D Fitts ◽  
R Bergthorsdottir ◽  
P Burman ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Crossover Trial ◽  
Prospective Trial ◽  
Time Profile ◽  
Open Label ◽  
Once Daily ◽  
Intercurrent Illness ◽  
Dual Release ◽  
Stage 1

ObjectiveThe objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).DesignRandomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.MethodsSixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).ResultsIn stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.ConclusionsThis long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

scholarly journals Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

2017 ◽  
Vol 176 (6) ◽  
pp. 715-725 ◽  
Author(s):  
Anna G Nilsson ◽  
Ragnhildur Bergthorsdottir ◽  
Pia Burman ◽  
Per Dahlqvist ◽  
Bertil Ekman ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Extension Study ◽  
Patient Treatment ◽  
Open Label ◽  
Once Daily ◽  
Intercurrent Illness ◽  
Glucocorticoid Replacement Therapy ◽  
Dual Release

Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S15) ◽  
pp. 22-30 ◽  
Author(s):  
Timothy E. Wilens ◽  
Thomas J. Spencer ◽  
Joseph Biederman
Keyword(s):  
Extended Release ◽  
Cardiovascular Effects ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Open Label Extension ◽  
Short And Long Term ◽  
Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

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.

Long-term safety and tolerability of iloperidone: results from a 25-week, open-label extension trial

CNS Spectrums ◽  
2013 ◽  
Vol 18 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Andrew J. Cutler ◽  
Amir H. Kalali ◽  
Greg W. Mattingly ◽  
Jelena Kunovac ◽  
Xiangyi Meng
Keyword(s):  
Serum Glucose ◽  
Favorable Effect ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Once Daily ◽  
Syndrome Scale ◽  
Open Label Extension ◽  
Negative Syndrome ◽  
Extension Trial

Introduction/ObjectiveLong-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of iloperidone.MethodsPatients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.ResultsA total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.Discussion/ConclusionThis study further supports the long-term safety and tolerability of iloperidone for the treatment of schizophrenia, including iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.

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