Safety Aspects of Immunoadsorption in IgG Removal Using a Single-Use, Multiple-pass Protein A Immunoadsorber (LIGASORB): Clinical Investigation in Healthy Volunteers

SummarySolulin is a novel recombinant soluble derivative of human thrombomodulin. In this first human study of Solulin, the safety, tolerability, pharmacokinetics and pharmacodynamics of Solulin in 30 healthy volunteers in response to single (0.6–30 mg) and 12 healthy volunteers in response to multiple (1 and 10 mg) ascending intravenous bolus doses compared to placebo are described. Solulin was shown to be well tolerated, and demonstrated linear pharmacokinetics over the clinically relevant dose range, with a plasma elimination half-life of 15–30 hours, indicating that a less than daily dose may be required for therapeutic use. Steady-state plasma levels after multiple dosing were reached after 48 hours. Solulin has shown to be able to inhibit thrombin generation without increasing levels of aPC/PCI complexes. Coagulation parameters INR and PT were not changed, aPTT was elevated to about 10% above the upper limit of normal after the highest single dose only. Thrombin clotting time was prolonged after administration of high dose Solulin (10, 30 mg). No effect on in vitro bleeding time has been found. There was no evidence of bleeding risk with Solulin administration. The pharmacodynamic effects correlated with Solulin plasma concentrations. This demonstrates that the antithrombotic effect of Solulin is predictable, suggesting that patient monitoring is not expected. The results of this study provide evidence that Solulin can be expected to be an effective and safe anticoagulant, and further clinical investigation is warranted.

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The selection of healthy volunteers for clinical investigation: the case for volunteer pools

Current Medical Research and Opinion ◽

10.1185/03007997609109302 ◽

1976 ◽

Vol 4 (3) ◽

pp. 192-196 ◽

Cited By ~ 2

Author(s):

Pieter Joubert ◽

Peter Pannall

Keyword(s):

Healthy Volunteers ◽

Clinical Investigation ◽

Selection Of

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Wireless Capsule Enteroscopy in Healthy Volunteers

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2016.93 ◽

2016 ◽

Vol 59 (3) ◽

pp. 79-83 ◽

Cited By ~ 1

Author(s):

Ilja Tachecí ◽

Petr Bradna ◽

Tomáš Douda ◽

Drahomíra Baštecká ◽

Marcela Kopáčová ◽

...

Keyword(s):

Healthy Volunteers ◽

Capsule Endoscopy ◽

Clinical Investigation ◽

Wireless Capsule Endoscopy ◽

Vascular Lesions ◽

Control Group ◽

Endoscopic Appearance ◽

Wireless Capsule ◽

Normal Laboratory

Introduction: The aim of our prospective study was to define endoscopy appearance of the small bowel in healthy volunteers. Method: Forty-two healthy volunteers underwent wireless capsule endoscopy, clinical investigation, laboratory tests, and completed a health-status questionnaire. All subjects were available for a 36-month clinical follow-up. Results: Eleven subjects (26%) had fully normal endoscopy findings. Remaining 31 persons (74%), being asymptomatic, with normal laboratory results, had some minor findings at wireless capsule endoscopy. Most of those heterogeneous findings were detected in the small intestine (27/31; 87%), like erosions and/or multiple red spots, diminutive polyps and tiny vascular lesions. During a 36-month clinical follow-up, all these 42 healthy volunteers remained asymptomatic, with fully normal laboratory control. Conclusions: Significant part of healthy subjects had abnormal findings at wireless capsule endoscopy. These findings had no clinical relevance, as all these persons remained fully asymptomatic during a 36-month follow-up. Such an endoscopic appearance would be previously evaluated as “pathological”. This is a principal report alerting that all findings of any control group of wireless capsule endoscopic studies must be evaluated with caution.

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Clinical Investigation of Topical Antimicrobials in Healthy Volunteers

Annals of Pharmacotherapy ◽

10.1177/106002809703100104 ◽

1997 ◽

Vol 31 (1) ◽

pp. 34-38 ◽

Cited By ~ 1

Author(s):

Jane H Langford ◽

Shalom I Benrimoj

Keyword(s):

Antibacterial Activity ◽

Healthy Volunteers ◽

Clinical Investigation ◽

Polymyxin B ◽

Onset Of Action ◽

Duration Of Action ◽

Drug Concentrations ◽

Clinical Investigations ◽

Forearm Skin

OBJECTIVE: To evaluate the antibacterial activity, onset of action, and duration of action of four topical antimicrobial gels containing cetrimide, bacitracin, polymyxin B sulfate, and a placebo gel. DESIGN: Multiples (1×, 2×, 4×, 8×) of minimally inhibitory in vitro drug concentrations were formulated in a gel vehicle. Antibacterial activity was evaluated using a scrub-wash methodology on artificially inoculated skin over an 8-hour study period. SETTING AND PARTICIPANTS: Healthy volunteers with intact forearm skin participated in the study. A standardized culture of Staphylococcus aureus NCTC 6571 was applied to four areas on each forearm, randomly assigned topical treatments were applied, and sites were sampled at predetermined time intervals using a surfactant wash fluid. OUTCOME MEASURES: Recovered bacteria were quantitated, allowing a comparison of antibacterial activity. RESULTS: Two-way and one-way ANOVA and a Scheffe test confirmed significant differences in antibacterial effect between the formulations containing 4 and 8 times the minimally inhibitory in vitro concentrations and placebo (p < 0.05). Duration of action was similar for all preparations; however, onset appeared to be faster with the formulations containing 4 and 8 times minimally inhibitory in vitro concentrations. CONCLUSIONS: The two topical preparations containing 4 and 8 times the minimally inhibitory in vitro concentrations of cetrimide, bacitracin, and polymyxin B sulfate demonstrated significant antibacterial activity and may have potential for further clinical investigations.

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Moving to CoPACaPAnA: Implementation of a continuous protein A capture process for antibody applications within an end-to-end single-use GMP manufacturing downstream process

Biotechnology Reports ◽

10.1016/j.btre.2020.e00465 ◽

2020 ◽

Vol 26 ◽

pp. e00465

Author(s):

Ozan Ötes ◽

Cathrin Bernhardt ◽

Kevin Brandt ◽

Hendrik Flato ◽

Otmar Klingler ◽

...

Keyword(s):

Protein A ◽

Downstream Process ◽

Capture Process ◽

Single Use ◽

End To End

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Feasibility study of a single-use balloon-assisted robotic colonoscope in healthy volunteers

Endoscopy International Open ◽

10.1055/a-1352-3688 ◽

2021 ◽

Vol 09 (04) ◽

pp. E537-E542

Author(s):

Chi-Chung Foo ◽

Wai-Keung Leung ◽

Thomas Ka-Luen Lui ◽

Jo Lai-Ken Cheung ◽

Kwok-Wai Lam ◽

...

Keyword(s):

Healthy Volunteers ◽

Disease Transmission ◽

Small Sample Size ◽

Prospective Trial ◽

Small Sample ◽

Cecal Intubation ◽

Feasible Alternative ◽

Single Use ◽

Technical Refinement ◽

Robotic Colonoscope

Abstract Background and study aims Despite its widespread adoption, colonoscope still has its limitations. Advancement is often limited by the looping of colon. The isolation of SARS-CoV-2 in stool raises concern for the risk of disease transmission. A single-use robotic colonoscope, the NISInspire-C System, that features a balloon-suction anchorage mechanism was developed to address these. Methods The NISInspire-C balloons are designed to provide anchorage for straightening of the colon during advancement. Angulation at the bending section is tendon-wire driven by servo mechanisms integrated into a robotic control console. This was a pilot, prospective trial to evaluate the safety and feasibility of this system. Healthy volunteers underwent examination with the NISInspire-C, followed by the conventional colonoscope. The procedure time, cecal intubation rates (CIR), complications, and level of pain were measured. Results A total of 19 subjects underwent the examination. The cecal intubation rate was 89.5 % (17/19) and the overall time-to-cecum was 26.3 minutes (SD: 17.9 mins). There were no procedure-related complications. Polyps were detected in seven of 19 (36.8 %) subjects during the NISInspire-C procedure. Three more subjects were found to have adenomatous polyps with the conventional colonoscope. There was minimal variation in level of pain during the procedures with the two colonoscopes. Conclusion The single-use robotic colonoscope NISInspire-C is a safe and feasible alternative to the conventional colonoscope. Further technical refinement is needed to improve the CIR. This study was limited by its small sample size.

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