Pharmacokinetics and Tolerance of the Phage Endolysin-Based Candidate Drug SAL200 after a Single Intravenous Administration among Healthy Volunteers

ABSTRACT This study was a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dosing, and dose-escalating study of intravenous SAL200. It is a new candidate drug for the treatment of antibiotic-resistant staphylococcal infections based on a recombinant form of the phage endolysin SAL-1. The study evaluated the pharmacokinetics, pharmacodynamics, and tolerance among healthy male volunteers after the intravenous infusion of single ascending doses of SAL200 (0.1, 0.3, 1, 3, and 10 mg/kg of body weight). SAL200 was well tolerated, and no serious adverse events (AEs) were observed in this clinical study. Most AEs were mild, self-limiting, and transient. The AEs reported in more than three participants were fatigue, rigors, headache, and myalgia. No clinically significant values with respect to the findings of clinical chemistry, hematology, and coagulation analyses, urinalysis, vital signs, and physical examinations were observed, and no notable trends in our electrocardiogram (ECG) results for any tested dose were noticed. A greater-than-dose-proportional increase with regard to systemic exposure and the maximum serum concentration was observed when the SAL200 dose was increased from 0.1 mg/kg to 10 mg/kg. This investigation constitutes the first-in-human phase 1 study of an intravenously administered, phage endolysin-based drug. (This study has been registered at ClinicalTrials.gov under identifier NCT01855048 and at the Clinical Research Information Service [https://cris.nih.go.kr/cris/ ] under identifier KCT0000968.).

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Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

Nature Medicine ◽

10.1038/s41591-021-01509-0 ◽

2021 ◽

Author(s):

Kathryn E. Stephenson ◽

Boris Julg ◽

C. Sabrina Tan ◽

Rebecca Zash ◽

Stephen R. Walsh ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Adverse Events ◽

Antiviral Activity ◽

Controlled Trial ◽

Phase 1 ◽

Serious Adverse Events ◽

Double Blind ◽

Cell Counts ◽

Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

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A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽

10.3390/vaccines8020296 ◽

2020 ◽

Vol 8 (2) ◽

pp. 296

Author(s):

Irina Kiseleva ◽

Irina Isakova-Sivak ◽

Marina Stukova ◽

Marianna Erofeeva ◽

Svetlana Donina ◽

...

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Phase 1 ◽

Healthy Adults ◽

Controlled Study ◽

Temperature Sensitive ◽

Serious Adverse Events ◽

Double Blind ◽

Human Influenza Virus ◽

Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

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1371. Safety, Tolerability, and Pharmacokinetics of Multiple Doses of TP-6076, a Novel, Fully Synthetic Tetracycline, in a Phase 1 Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1202 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S420-S420 ◽

Cited By ~ 3

Author(s):

Larry Tsai ◽

Alison Moore

Keyword(s):

Physical Examination ◽

Bacterial Infections ◽

Clinical Laboratory ◽

Phase 1 ◽

Geometric Mean ◽

Vital Signs ◽

Gastrointestinal Adverse Event ◽

Double Blind ◽

Dose Study

Abstract Background TP-6076 is a novel, fully synthetic tetracycline being developed for the treatment of serious bacterial infections, including those caused by multidrug-resistant Acinetobacter baumannii. TP-6076 has demonstrated potent activity in vitro against carbapenem-resistant strains of A. baumannii, with MIC90 64 times lower compared with tigecycline and 256 times lower compared with minocycline. We now report the results of a multiple ascending dose study in normal healthy volunteers. Methods This was a phase 1, single-site, randomized, double-blind, placebo-controlled dose-escalating, multiple dose study in healthy adults who met the inclusion/exclusion criteria and provided informed consent prior to any study procedure. Cohorts of eight subjects each (six active and two placebo) received daily doses of 6.0 to 40.0 mg TP-6076 or placebo for 7 days. Plasma and urine samples for pharmacokinetic (PK) analyses were collected starting immediately prior to dosing until 96 hours after the last dose. Safety was assessed through collection of adverse events (AEs), clinical laboratories, vital signs, ECG, and physical examination data. Results The geometric mean derived PK parameters for TP-6076 were: There were no serious or severe AEs reported. The most frequently reported AEs were gastrointestinal events, including nausea and vomiting, and localized infusion site reactions. There were no clinically significant changes in clinical laboratory values, ECG parameters, or physical examination findings. Conclusion Following multiple IV doses of TP-6076, plasma exposure increased as dose increased. Multiple IV doses of TP-6076 were generally well tolerated, with higher gastrointestinal adverse event rates in the higher dose groups. Disclosures L. Tsai, Tetraphase Pharmaceuticals: Employee and Shareholder, Salary. A. Moore, Tetraphase Pharmaceuticals: Employee, Salary.

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First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00969-19 ◽

2019 ◽

Vol 63 (11) ◽

Cited By ~ 3

Author(s):

Mammen P. Mammen ◽

Danielle Armas ◽

Frank H. Hughes ◽

Andrew M. Hopkins ◽

Cindy L. Fisher ◽

...

Keyword(s):

Adverse Events ◽

Phase 1 ◽

Safety Data ◽

Healthy Adults ◽

Antifungal Drug ◽

Renal Elimination ◽

Serious Adverse Events ◽

Dose Escalation Study ◽

Double Blind ◽

Time Curve

ABSTRACT VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study, was conducted in healthy adults to determine the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (i.v.) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing cohort prior to recommending the initiation of each subsequent cohort. No serious adverse events (SAEs) occurred; the majority of treatment-emergent adverse events (TEAEs) were mild and self-limited. The most common drug-related TEAEs were infusion site reactions. No clinically concerning trends were noted in vital signs, electrocardiograms, physical examinations, or safety laboratory results. Following single infusions of VL-2397, the overall and maximum exposures rose less than proportionally with increasing doses from 3 mg to 1,200 mg as indicated by area under the concentration-time curve over 24 h (AUC24) and maximum concentration (Cmax). No signs of VL-2397 accumulation were observed following i.v. infusions of 300, 600, and 1,200 mg every 24 h (q24h) for 7 days. Renal elimination played a major role in total body clearance, with up to 47% of unmetabolized drug in urine 24 h after administration at single doses of >30 mg. Overall, VL-2397 dosing in the study appeared to be safe and well tolerated in the healthy subjects. The safety profile, consistent PK, and lack of drug accumulation support further development of VL-2397 in patients with invasive aspergillosis.

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1099. Evaluation of the Safety and Pharmacokinetics (PK) following Administration of Single and Multiple Doses of Anti-Staphylococcal Lysin, LSVT-1701, in Healthy Adult Subjects

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1293 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S641-S641

Author(s):

Mary Beth Wire ◽

Soo youn Jun ◽

In-Jin Jany ◽

Jun Gi Hwang ◽

David Huang

Keyword(s):

Single Dose ◽

Healthy Adult ◽

Phase 1 ◽

Vital Signs ◽

Time Data ◽

Serum Samples ◽

Double Blind ◽

Dose Study ◽

Clinically Significant ◽

New Treatments

Abstract Background LSVT-1701 is an anti-staphylococcal phage lysin being developed for treatment of MRSA infections in combination with SoC antibiotics. The safety and PK of single ascending doses of LSVT-1701 0.1 to 10 mg/kg in healthy adult volunteers were previously described (Jun, et.al, AAC 2017;61:e02629-16). We further evaluated the safety and PK of multiple ascending doses of LSVT-1701 in healthy adult subjects. Methods Study ITB-101-1b was a Phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose study. 8 subjects were randomized 3:1 to active:placebo in each cohort. LSVT-1701 was administered as a 6 mg/kg single dose and twice daily (BID) doses of 1.5, 3.0, and 4.5 mg/kg for 4 days (24h between Doses 1-2, 12h between Doses 2-6). Study drugs were administered as a 1-hour IV infusion. Serial serum samples were collected over 24 hours following the first and last doses for measurement of LSVT-1701 concentrations by a validated ELISA method. PK analysis of LSVT-1701 concentration-time data was done using noncompartmental methods. Safety was assessed by AEs, clinical labs, vital signs, and ECG. Results 30/32 (94%) subjects completed the study. No subjects withdrew due to AEs, and there were no severe AEs, no serious AEs, and no deaths. AEs were of mild (97%) to moderate (3%) intensity and were reported by all subjects in the LSVT-1701 6 mg/kg single dose group and 1-3 (17-50%) of subjects receiving 1.5 to 4.5 mg/kg BID or placebo. The most common AEs of headache, chills, rigors, and fever generally lasted for ≤2 days with or without acetaminophen treatment, and no clinically significant changes in blood pressure, heart rate, ECG, or clinical labs (other than transient increases in CRP) were observed. Infusion site reactions (erythema, pain, induration, warmth) were observed with BID administration of LSVT-1701, but not with the single 6 mg/kg dose or placebo. LSVT-1701 exposure increased greater than in proportion to dose and t1/2 was concentration-dependent, increasing with higher doses. No accumulation in LSVT-1701 exposure was observed. Summary of LSVT-1701 PK Parameters Summary of LSVT-1701 PK Parameters Conclusion The safety and PK profile of LSVT-1701 is favorable for evaluation in patients with S. aureus infections, including bacteremia and infective endocarditis, for which new treatments are needed. Disclosures Mary Beth Wire, Pharm#, Lysovant (Consultant) Soo youn Jun, PhD, iNtRON Biotechnology (Consultant) In-Jin Jany, PhD, iNtRON (Consultant) Jun Gi Hwang, PhD, Lysovant (Consultant) David Huang, MD, PhD, Lysovant (Consultant)

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First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of SPR720, a Novel Oral Bacterial DNA Gyrase (GyrB) Inhibitor for Mycobacterial Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01208-21 ◽

2021 ◽

Author(s):

Angela K. Talley ◽

Archie Thurston ◽

Grayson Moore ◽

Vipul K. Gupta ◽

Myriah Satterfield ◽

...

Keyword(s):

Adverse Events ◽

Phase 1 ◽

Human Study ◽

Dna Gyrase ◽

Plasma Exposure ◽

Serious Adverse Events ◽

Double Blind ◽

Bacterial Dna ◽

Elimination Pathway

SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis. SPR719 has demonstrated activity against clinically relevant mycobacteria in vitro and in murine and hollow fiber infection models. This Phase 1 randomized, double-blind, placebo-controlled, single ascending dose (SAD)/multiple ascending dose (MAD) trial evaluated the safety, tolerability, and pharmacokinetics of SPR720/SPR719. A total of 96 healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 (or placebo) as single oral doses ranging from 100 mg to 2000 mg, or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events (AEs) were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. The median SPR719 T max ranged from 2.8 to 8.0 hours across cohorts, and the t 1/2 ranged from 2.9 to 4.5 hours and was shown to be dose-independent. Dosing with food decreased SPR719 plasma exposure by approximately 20%. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Days 1 and 7, suggesting induction of an elimination pathway. However, plasma AUC 0-24 was comparable between Days 7 and 14. Results of this first-in-human study suggest that predicted therapeutic exposures of SPR719 can be attained with a once-daily oral administration of SPR720.

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Inhibition of Interleukin-6 (IL-6) Reverses Anemia In Patients with Advanced Non Small Cell Lung Cancer (NSCLC): Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Blood ◽

10.1182/blood.v116.21.640.640 ◽

2010 ◽

Vol 116 (21) ◽

pp. 640-640 ◽

Cited By ~ 1

Author(s):

Michael W. Schuster ◽

James R Rigas ◽

Sergey V Orlov ◽

Branislav Milovanovic ◽

Kumar Prabhash ◽

...

Keyword(s):

Adverse Events ◽

Clinical Chemistry ◽

Controlled Trial ◽

Safety Data ◽

Primary Objective ◽

Serious Adverse Events ◽

Double Blind ◽

Reactive Protein ◽

Grade 3 ◽

Cancer Related Anemia

Abstract Abstract 640 Background: ALD518 is a humanized, desialyated anti-IL-6 antibody being developed for the treatment of cancer-related anemia, cachexia and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518 in patients with advanced NSCLC. Secondary objectives examined hematologic parameters. Methods: 124 patients with NSCLC, ECOG 0–3, weight loss in the preceding 3 months of >5% body weight, hemoglobin (Hb) >7g/dL, and C-reactive protein (CRP) >10mg/L were dosed. Patients were randomized to 1 of 4 groups (n~30/group). Placebo or ALD518 80mg, 160mg, or 320mg was administered intravenously every 8 weeks. Pts were followed up for 24 weeks. Data included hematologic parameters, clinical chemistry, CRP, D-dimer, lean body mass and adverse events (AEs). Quality of life data included the FACIT-F, FACT-L, and FAACT questionnaires. Data presented in this abstract relates to the safety and hematology results. Results: 29 pts completed the study treatments and evaluations, 38 failed to complete every visit, 52 died of progressive disease, and 5 withdrew because of adverse events. There were no dose limiting toxicities (DLTs), infusion reactions, or anti-idiotypic antibody responses to ALD518 observed in the study. 84 pts had serious AEs of which 1 was deemed to be possibly related to administration of ALD518 (rectal hemorrhage). The majority of the serious adverse events were due to progression of the NSCLC. Six patients had a CTC grade 4 change in laboratory safety data during the study. Four patients experienced a grade 4 hypercalcemia: 1 (3.6%), 2 (6.1%), and 1 (3.2%) in the ALD518 80mg, 160mg and placebo groups, respectively, and there was 1 patient with grade 4 GGT elevation (placebo) and 1 patient with grade 4 hypokalemia (ALD518 160mg). There were no treatment related differences in vitals sign or 12-lead ECG data. The mean (±SD) values for Hb, hematocrit (Hct), mean corpuscular Hb (MCH) and platelet counts are listed below: 38/93 pts treated with ALD518 and 10/31 given placebo had a pre-dose Hb =< 11g/dL. 24 of these pts on ALD518 and 7 of these pts on placebo remained in the study at week 4. 14/24 pts on ALD518 and 0/7 on placebo had raised their Hb from =< 11g/dL to >= 12g/dL. Conclusions: ALD518 increased Hb, Hct, MCH in NSCLC pts and raised Hb to >= 12g/dL in 58% of pts with a Hb =< 11g/dL at baseline. There was also a modest fall in platelet count observed in patients treated with ALD518 but no patients had a CTC grade 4 thrombocytopenia and only one patient (ALD518 160mg group) had a grade 3 thrombocytopenia at one time point. There were no major safety signals related to the administration of ALD518. Further study of ALD518 as a novel non-erythropoietic stimulating agent for cancer-related anemia is warranted. Disclosures: Schuster: Alder Biopharmaceuticals Inc: Honoraria. Rigas: Alder Biopharmaceuticals inc: Honoraria. Smith:Alder Biopharmaceuticals Inc: Employment.

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Pharmacokinetics and Short-Term Safety of 873140, a Novel CCR5 Antagonist, in Healthy Adult Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.7.2802-2806.2005 ◽

2005 ◽

Vol 49 (7) ◽

pp. 2802-2806 ◽

Cited By ~ 22

Author(s):

Kimberly K. Adkison ◽

Anne Shachoy-Clark ◽

Lei Fang ◽

Yu Lou ◽

Kathy O'Mara ◽

...

Keyword(s):

Adverse Events ◽

Dose Escalation ◽

Maximum Concentration ◽

Vital Signs ◽

Time Profile ◽

Ccr5 Antagonist ◽

Repeat Dose ◽

Serious Adverse Events ◽

Double Blind

ABSTRACT 873140 is a novel CCR5 antagonist with potent in vitro anti-human immunodeficiency virus (HIV) activity. This study was a double-blind, randomized, placebo-controlled, single- and repeat-dose escalation investigation of the safety, pharmacokinetics, and food effect of 873140 in 70 adult subjects. During single-dose escalation, three cohorts (each composed of 10 subjects, with 8 subjects receiving the active drug and 2 subjects receiving the placebo [8 active and 2 placebo]) received doses of 50, 200, 400, 800, and 1,200 mg after an overnight fast, or 400 mg plus a standard high-fat breakfast in an alternating panel design. During repeat-dose escalation, four cohorts (each with 8 active and 2 placebo) received doses of 200, 400, 600, or 800 mg every 12 h (BID) for 8 days. Laboratory safety tests, vital signs, and electrocardiograms (ECGs) were performed at regular intervals, and blood samples were obtained for pharmacokinetics. Single and repeat doses of 50 mg to 800 mg were well tolerated, with no serious adverse events and no grade 3 or 4 adverse events. The mild-to-moderate side effects were primarily gastrointestinal and included abdominal cramping, nausea, and diarrhea. No specific trends in laboratory parameters or clinically significant ECG changes were noted. Plasma 873140 concentrations increased rapidly; the median time to maximum concentration of drug in serum was 1.75 to 5 h. The median area under the plasma concentration-time profile (AUC) and the maximum concentration of drug in serum (C max) ranged from 127 ng · h/ml and 24 ng/ml at 200 mg BID to 329 ng · h/ml and 100 ng/ml at 800 mg BID, respectively. Food consumption increased the AUC and C max by a mean of 1.7- and 2.2-fold, respectively. The pharmacokinetic and safety profile supports the continued investigation of 873140 with HIV-infected subjects.

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0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients

SLEEP ◽

10.1093/sleep/zsaa056.144 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A58-A58

Author(s):

M Uchiyama ◽

D Kambe ◽

Y Imadera ◽

H Sunaga ◽

S Hasegawa ◽

...

Keyword(s):

Receptor Antagonist ◽

Healthy Subjects ◽

Phase 1 ◽

Sleep Onset ◽

Pharmacokinetic Profile ◽

Residual Effects ◽

Digit Symbol Substitution Test ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind

Abstract Introduction TS-142 is a novel dual orexin receptor antagonist (DORA) developed for the treatment of insomnia. Here we report its pharmacokinetic profile in the healthy subjects and its efficacy and safety in patients with insomnia. Methods A phase1 study was conducted to clarify pharmacokinetic profile, in which various doses of TS-142 (1–30 mg) were orally administered once to thirty two healthy subjects. Subsequently, a phase 2a study utilizing polysomnography (PSG) was carried out in patients with primary insomnia, in which 5, 10, or 30 mg of TS-142, or placebo was randomly administered in a double-blind manner. Karolinska Sleepiness Scale (KSS) and Digit Symbol Substitution Test (DSST) were also examined in the morning after PSG. Results Following single administration of TS-142, plasma concentration of unchanged compound reached maximum within 2.50 h (median), and then eliminated rapidly, giving mean elimination half-life between 1.32 and 3.25 h. Twenty-three patients with insomnia completed the Phase2a study. Both latency to persistent sleep (LPS) and wake after sleep onset (WASO) were significantly improved with TS-142 at all doses, in comparison with placebo (-42, -42 and -45 for LPS [min] and -28, -35 and -55 for WASO [min] in 5, 10, 30 mg, respectively). KSS and DSST administered in the morning indicated no serious hangover effects. No serious adverse events were observed in these trials. Conclusion The phase 1 trial showed favorable pharmacokinetic profiles. The phase 2a trial demonstrated that TS-142 was efficacious in objective sleep onset and maintenance with minimal next-day residual effects. TS-142 was generally well tolerated in both studies. Support Taisho Pharmaceutical. Co., Ltd.

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Safety and efficacy of glycopyrrolate as a premedication for endoscopic submucosal dissection: a randomized, double-blind, placebo-controlled study

Endoscopy ◽

10.1055/s-0043-112491 ◽

2017 ◽

Vol 49 (10) ◽

pp. 949-956 ◽

Cited By ~ 1

Author(s):

Eui Kim ◽

Min Um ◽

Kyoung Kim ◽

Jung Kim ◽

Su Kim ◽

...

Keyword(s):

Adverse Events ◽

Endoscopic Submucosal Dissection ◽

Medical Center ◽

Controlled Trial ◽

Controlled Study ◽

Research Information ◽

Serious Adverse Events ◽

Double Blind ◽

Double Blind Placebo ◽

Submucosal Dissection

Abstract Background and study aims Anticholinergic premedication has not been validated for endoscopic submucosal dissection (ESD). In this randomized, double-blind, placebo-controlled trial, we investigated the efficacy and safety of glycopyrrolate as a premedication for ESD. Methods A total of 196 patients undergoing ESD at a single tertiary medical center between December 2014 and February 2016 were randomly allocated to receive one of the following two premedications: glycopyrrolate (0.004 mg/kg intramuscularly [IM]) or placebo (2.0 mL normal saline solution IM). All patients received the premedication 30 minutes prior to ESD in a double-blind manner. The endoscopists reported the ease of performing the procedure and the incidence of secretion-induced hypoxemia, cough, and other procedure-related adverse events. Results Glycopyrrolate and placebo were received by 96 and 100 patients, respectively. ESD was successfully performed in all patients without any serious adverse events related to sedation or ESD. The median visual analog scale for procedure ease was higher in the glycopyrrolate group at 8 (interquartile range [IQR] 7 – 9) vs. 7 (IQR 6 – 8.25); P < 0.001. The proportions of patients with secretion-induced hypoxemia (4.4 % vs. 14.3 %; P = 0.03) and cough (16.7 % vs. 35.7 %; P = 0.005) were lower in the glycopyrrolate group. Conclusions The use of glycopyrrolate as a premedication for ESD significantly improved the ease of performing the procedure and reduced the incidence of secretion-induced hypoxemia and cough during ESD. Glycopyrrolate may be a promising premedication to ensure safe and stable ESD procedures.Trial registration: Clinical Research Information Service (CRIS): KCT0001540.

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