An Open-Label Dose-Escalation Study of Once-Daily and Twice-Daily Pasireotide in Healthy Volunteers

2014 ◽  
Vol 21 (3) ◽  
pp. 164-173 ◽  
Author(s):  
Magdy Shenouda ◽  
Mario Maldonado ◽  
Yanfeng Wang ◽  
Emmanuel Bouillaud ◽  
Michelle Hudson ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Dose Escalation ◽  
Open Label ◽  
Dose Escalation Study ◽  
Once Daily ◽  
Label Dose

scholarly journals Open-Label, Dose Escalation Study of the Safety and Pharmacokinetic Profile of Tefibazumab in Healthy Volunteers

2005 ◽  
Vol 49 (3) ◽  
pp. 959-962 ◽  
Author(s):  
Sandra Reilley ◽  
Eric Wenzel ◽  
Laurie Reynolds ◽  
Beth Bennett ◽  
Joseph M. Patti ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Dose Escalation ◽  
Maximum Concentration ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Open Label ◽  
Serious Adverse Events ◽  
Dose Escalation Study ◽  
Label Dose ◽  
The Mean

ABSTRACT Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of Staphylococcus aureus infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (C max) of 59, 127, 252, and 492 μg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (T max) was 1.0 h for each dose. The mean elimination half-life (t 1/2) was approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 μg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 μg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.

scholarly journals A Phase I, open-label, dose-escalation study of continuous once-daily oral treatment with afatinib in patients with advanced solid tumors

2012 ◽  
Vol 31 (2) ◽  
pp. 409-416 ◽  
Author(s):  
Michael S. Gordon ◽  
David S. Mendelson ◽  
Mitchell Gross ◽  
Martina Uttenreuther-Fischer ◽  
Mahmoud Ould-Kaci ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Oral Treatment ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Dose Escalation Study ◽  
Once Daily ◽  
Label Dose

Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: A 29-day, multicenter, open-Label, dose-escalation study

2006 ◽  
Vol 28 (10) ◽  
pp. 1607-1618 ◽  
Author(s):  
Ronald A. Thisted ◽  
Leslie Klaff ◽  
Sherwyn L. Schwartz ◽  
James P. Wymer ◽  
Neil W. Culligan ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dose Escalation ◽  
Diabetic Peripheral Neuropathy ◽  
Adult Patients ◽  
Open Label ◽  
Dose Escalation Study ◽  
Painful Diabetic Peripheral Neuropathy ◽  
Label Dose

scholarly journals A phase 1/2, open‐label, dose‐escalation study of midostaurin in children with relapsed or refractory acute leukaemia

2018 ◽  
Vol 185 (3) ◽  
pp. 623-627 ◽  
Author(s):  
C. Michel Zwaan ◽  
Stefan Söderhäll ◽  
Benoit Brethon ◽  
Matteo Luciani ◽  
Carmelo Rizzari ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Acute Leukaemia ◽  
Phase 1 ◽  
Open Label ◽  
Dose Escalation Study ◽  
Label Dose

scholarly journals MON-282 Treatment of Hyperprolactinemia with Ropinirole: An Open-Label Dose Escalation Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amanda Tsang ◽  
Cara Dimino ◽  
Alexander G Khandji ◽  
Sunil Kumar Panigrahi ◽  
Gabrielle Page-Wilson
Keyword(s):  
Dose Escalation ◽  
Tumor Size ◽  
Low Cost ◽  
Total Daily Dose ◽  
Open Label ◽  
Dose Escalation Study ◽  
Biochemical Status ◽  
Label Dose ◽  
Study Completion ◽  
Cardiac Valve Disease

Abstract Purpose Treatment of hyperprolactinemia and prolactinomas with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. Ropinirole (ROP) is a low cost selective D2/D3 receptor non-ergot DA, approved for treatment of Parkinson’s disease and Restless Leg Syndrome, that has been shown to acutely lower prolactin levels (PRL). This study investigated the efficacy and tolerability of long-term ROP therapy in patients with hyperprolactinemia. Methods & Results Ten healthy women (21-45 yrs) with hyperprolactinemia were treated with ROP (0.25-6.0mg/d) for 6 months in an open-label dose escalation study. Clinical and biochemical status was assessed monthly and ROP doses were up-titrated to achieve normal PRL levels, restore menses, and eliminate galactorrhea. Two subjects had macroprolactinomas, 7 had microprolactinomas, and 1 had idiopathic hyperprolactinemia. 8/10 had previously been treated with cabergoline and/or bromocriptine. 5/10 were intolerant and 1/10 was resistant to ergot DAs. Pituitary MRIs were performed at baseline and 6 months.ROP was initiated at 0.25mg QHS in 9/10 subjects. One subject with severe DA intolerance was initiated on 0.125mg QHS. Subjects reaching a total daily dose (TDD) > 2.0mg/d were transitioned to ROP extended release. At study completion, TDDs ranged from 1-6mg/d, with a median TDD of 2mg/d. Baseline PRL levels were 136 ± 49ng/ml (1.9-25ng/ml). Stable PRL normalization was achieved in 50% of subjects. Of the subjects achieving normal PRL, 4 had microadenomas and 1 had idiopathic hyperprolactinemia, and the median effective TDD was 1mg/d (1-4mg/d, range). Among those not achieving PRL normalization, PRL decreased 46 ± 5.4% (Mean ± SEM) from baseline, at a median TDD of 4.0mg/d (2-6mg/d, range). In the subject with documented resistance to ergot DAs, PRL decreased from 529 to 320ng/ml, after 3 months of ROP on the maximum dose studied (6mg/d), but rose to 690ng/ml at 6 months. During ROP treatment, menses normalized in 57%, and galactorrhea resolved in 67% of affected subjects. At study completion, tumor size was unchanged in 7/8 prolactinomas. A 20% decrease in tumor size was observed in one macroadenoma, accompanied by a 30% reduction in PRL levels. There were no changes in BP, HR, weight, renal or kidney function. Mild adverse effects (AEs) were recorded in 80% of subjects. Fatigue (60%), nausea (40%), and headache (20%) were most common. Reported AEs declined after month 1 and ROP was not discontinued due to intolerance. Conclusion These data provide support for the efficacy of ROP in the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia. While further study is needed, ROP treatment for hyperprolactinemia could be considered in patients with ergot DA intolerance or significant cardiac valve disease.

scholarly journals Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study

The Lancet ◽  
2014 ◽  
Vol 384 (9942) ◽  
pp. 504-513 ◽  
Author(s):  
Vincenzo Libri ◽  
Cihangir Yandim ◽  
Stavros Athanasopoulos ◽  
Naomi Loyse ◽  
Theona Natisvili ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
High Dose ◽  
Open Label ◽  
Dose Escalation Study ◽  
Label Dose ◽  
Neurological Effects

Phase 1, open-label, dose-escalation study of sorafenib in combination with eribulin in patients with advanced, metastatic, or refractory solid tumors

2018 ◽  
Vol 81 (4) ◽  
pp. 727-737 ◽  
Author(s):  
Frederik Marmé ◽  
Carlos Gomez-Roca ◽  
Kristina Graudenz ◽  
Funan Huang ◽  
John Lettieri ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Open Label ◽  
Dose Escalation Study ◽  
Label Dose
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