scholarly journals Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

2019 ◽  
Vol 104 (11) ◽  
pp. 5136-5147 ◽  
Author(s):  
Michael Mannstadt ◽  
Bart L Clarke ◽  
John P Bilezikian ◽  
Henry Bone ◽  
Douglas Denham ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Urinary Calcium ◽  
Open Label ◽  
Oral Calcium ◽  
Efficacy Outcome ◽  
Open Label Extension ◽  
Calcium Phosphorus ◽  
Safety Parameters ◽  
Turnover Markers

Abstract Context Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. Objective To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. Design Open-label extension study; 5-year interim analysis. Setting 12 US centers. Patients Adults (N = 49) with chronic hypoparathyroidism. Intervention(s) rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum. Main Outcome Measure(s) Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal. Results Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline. Conclusion Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.

scholarly journals Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001649
Author(s):  
John B Buse ◽  
Bruce W Bode ◽  
Ann Mertens ◽  
Young Min Cho ◽  
Erik Christiansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Dose Adjustment ◽  
Main Phase ◽  
Open Label ◽  
Open Label Extension ◽  
Registration Number ◽  
Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

scholarly journals Long‐term safety and efficacy of add‐on cannabidiol in patients with Lennox–Gastaut syndrome: Results of a long‐term open‐label extension trial

Epilepsia ◽  
2021 ◽  
Author(s):  
Anup D. Patel ◽  
Maria Mazurkiewicz‐Bełdzińska ◽  
Richard F. Chin ◽  
Antonio Gil‐Nagel ◽  
Boudewijn Gunning ◽  
...  
Keyword(s):  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Extension Trial

scholarly journals Long‐term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open‐label extension of a randomized clinical study

Epilepsia ◽  
2021 ◽  
Author(s):  
Jacqueline A. French ◽  
Steve S. Chung ◽  
Gregory L. Krauss ◽  
Sang Kun Lee ◽  
Maciej Maciejowski ◽  
...  
Keyword(s):  
Clinical Study ◽  
Open Label ◽  
Focal Seizures ◽  
Randomized Clinical Study ◽  
Open Label Extension

scholarly journals Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension

Thorax ◽  
2017 ◽  
Vol 73 (6) ◽  
pp. 581-583 ◽  
Author(s):  
Luca Richeldi ◽  
Michael Kreuter ◽  
Moisés Selman ◽  
Bruno Crestani ◽  
Anne-Marie Kirsten ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Term Treatment ◽  
Adverse Event Profile ◽  
Open Label ◽  
Comparator Group ◽  
Long Term Treatment ◽  
Open Label Extension ◽  
Rate Of Decline

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was −125.4 mL/year (95% CI −168.1 to −82.7) in the nintedanib group and −189.7 mL/year (95% CI −229.8 to −149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks.

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