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 Pharmacokinetics and Safety Profile of the Human Anti-Pseudomonas aeruginosa Serotype O11 Immunoglobulin M Monoclonal Antibody KBPA-101 in Healthy Volunteers

2009 ◽  
Vol 53 (8) ◽  
pp. 3442-3446 ◽  
Author(s):  
Hedvika Lazar ◽  
Michael P. Horn ◽  
Adrian W. Zuercher ◽  
Martin A. Imboden ◽  
Peter Durrer ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Pseudomonas Aeruginosa ◽  
Body Weight ◽  
Healthy Volunteers ◽  
Human Monoclonal Antibody ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Immunoglobulin M ◽  
Serious Adverse Events ◽  
The Mean

ABSTRACT KBPA-101 is a human monoclonal antibody of the immunoglobulin M isotype, which is directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11. This double-blind, dose escalation study evaluated the safety and pharmacokinetics of KBPA-101 in 32 healthy volunteers aged 19 to 46 years. Each subject received a single intravenous infusion of KBPA-101 at a dose of 0.1, 0.4, 1.2, or 4 mg/kg of body weight or placebo infused over 2 h. Plasma samples for pharmacokinetic assessments were taken before infusion as well as 0.25, 0.5, 1, 2, 2.5, 4, 6, 8, 12, 24, 36, and 48 h and 4, 7, 10, and 14 days after start of dosing. Plasma concentrations of KBPA-101 were detected with mean maximum concentrations of drug in plasma of 1,877, 7,571, 24,923, and 83,197 ng/ml following doses of 0.1, 0.4, 1.2, and 4.0 mg/kg body weight, respectively. The mean elimination half-life was between 70 and 95 h. The mean volume of distribution was between 4.76 and 5.47 liters. Clearance ranged between 0.039 and 0.120 liters/h. At the highest dose of 4.0 mg/kg, plasma KBPA-101 levels were greater than 5,000 ng/ml for 14 days. KBPA-101 exhibited linear kinetics across all doses. No anti-KBPA-101 antibodies were detected after dosing in any subject. Overall, the human monoclonal antibody KBPA-101 was well tolerated over the entire dose range in healthy volunteers, and no serious adverse events have been reported.

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

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

Phase I open-label, dose escalation of YH003, an anti-CD40 monoclonal antibody in combination with toripalimab (anti-PD-1 mAb) in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2580-2580
Author(s):  
Jermaine Coward ◽  
Afaf Abed ◽  
Adnan Nagrial ◽  
Ben Markman
Keyword(s):  
Monoclonal Antibody ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Dose Escalation Study ◽  
Label Dose ◽  
Febrile Episodes ◽  
Antigen Presenting

2580 Background: YH003, a recombinant, humanized agonistic anti-CD40 IgG2 monoclonal antibody (mAb) specifically recognizes and agonizes CD40 on the antigen-presenting cells to enhance immune responses. Preclinical data have shown potent anti-cancer activity when combined with anti-PD-1 antibodies. Methods: This is an ongoing phase 1 dose-escalation study. Patients with advanced solid tumors receive YH003 by IV administration Q3W as monotherapy at 0.03 to 3.0 mg/kg for the first cycle (21 days) then in combination with Toripalimab at 240 mg Q3W for the 4 subsequent cycles in an accelerated “3+3” design. The safety, tolerability and preliminary efficacy data will be analyzed. Results: As of 31 Dec 2020 data cutoff, 9 patients (pts) were enrolled and treated at 0.03 mg/kg (n = 3), 0.1mg/kg (n = 3), and 0.3mg/kg (n = 3). The median age was 63 years (range 33-68). Baseline ECOG scores were 0 (7 pts) and 1 (2 pts) with a median of 2 prior lines therapy (range 1-7). 5 pts had received prior immunotherapy (PD-1/PD-L1 or PD-1+CTLA-4). As of data cutoff, no dose limiting toxicities (DLT) were observed. No Serious Adverse Event (SAE) or AEs leading to treatment discontinuation were reported. Four drug related AEs were reported including one Grade 1 (G1) choroidal thickening (related to YH003) at 0.03 mg/kg, one G1 fatigue (related to YH003) at 0.1 mg/kg, two G1 febrile episodes (one related to YH003 and the other related to combination treatment) at 0.3 mg/kg. Among 5 patients assessable for response, there were 2 SD (one with anti-PDL1 refractory Merkel cell carcinoma at 0.03 mg/kg and one with anti-PD1 refractory NSCLC at 0.1 mg/kg) and 1 PR with anti-PD1/anti-CTLA4 refractory ocular melanoma at 0.1 mg/kg. Conclusions: YH003 was well tolerated up to 0.3 mg/kg dose levels when combined with Toripalimab and has shown encouraging antitumor activity in patients with advanced solid tumors. Clinical trial information: NCT04481009.

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