MO258SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF VIS649, AN APRIL-NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, IN HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yusuke Suzuki ◽  
Mohit Mathur ◽  
Jonathan Barratt ◽  
Frank Engler ◽  
Jill Yarbrough ◽  
...  
Keyword(s):  
Phase 1 ◽  
Study Drug ◽  
Dependent Manner ◽  
Double Blind ◽  
Serum Iga ◽  
Dose Study ◽  
Dose Response Effect ◽  
Japanese Descent ◽  
Dose Dependent ◽  
Single Ascending Dose Study

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy (IgAN) is a glomerulonephritis characterized by the presence of circulating and glomerular immune complexes containing galactose-deficient (Gd) IgA1. A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily of ligands, is thought to play a key role in the pathogenesis of IgAN by virtue of its role in class-switching to IgA production. VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of APRIL, is in clinical development as a potential treatment for IgAN. The primary objective of this first-in-human study was to evaluate the safety and tolerability of VIS649 in healthy volunteers. Secondary objectives included characterization of the pharmacokinetics (PK) and pharmacodynamics (PD) of VIS649. Method This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study of VIS649 in healthy adult male and female volunteers (ClinicalTrials.gov identifier: NCT03719443). The study was conducted in sequential dosing cohorts. The first four cohorts (0.5, 2.0, 6.0, and 12.0 mg/kg, respectively) each enrolled 9 participants (4 of Japanese descent and 5 of non-Japanese descent) who were randomized to VIS649 or placebo in a ratio of 7:2. In addition, a fifth cohort enrolled 15 adults randomized to receive VIS649 6.0 mg/kg or placebo (10:5), followed by tetanus/diphtheria vaccine challenge after 28 days (TENIVAC®, Sanofi Pasteur Limited; the effect of APRIL inhibition on vaccine response is described in a companion abstract). Participants received intravenous administration of study drug on Day 1, were discharged from the institution on Day 2, and were followed for 16–24 weeks on an outpatient basis. Standard safety assessments and blood sampling for PK and PD were performed at regular intervals. Results 51 participants were randomized and dosed with study drug, of whom 47 (92.2%) completed the study. VIS649 was well tolerated, with no serious adverse events (AEs) or AEs that led to study discontinuation. Most treatment-emergent AEs (TEAEs) were mild; the incidence and severity of TEAEs were not dose dependent. One participant in the 2.0 mg/kg group experienced a severe TEAE of syncope following phlebotomy that the investigator considered unlikely to be related to study drug. There was no clinically relevant effect of treatment on laboratory tests, vital signs, electrocardiogram parameters, or physical examinations. VIS649 had non-linear PK: half-life (t½) increased with dose, while drug exposure (AUC) increased in a greater than dose proportional manner. Serum IgA, Gd-IgA1, IgG, and IgM were reversibly suppressed in a dose-dependent manner following VIS649 administration. The maximum mean percentage reductions from baseline occurred at Week 12 for the 12.0 mg/kg dose: IgA, -57.2% (Figure); Gd-IgA1, -71.6% (Figure); IgG, -33.6%; and IgM, -67.2%. These reductions were reversible and showed a dose-response effect with respect to time-to-recovery. Mean free (non-VIS649 bound) serum APRIL levels decreased to the lower limit of quantification (50 pg/mL) for all VIS649 doses at Week 1, and also showed a dose-response effect with respect to time-to-recovery. No depletions in circulating lymphocyte populations were observed. There were no significant PK or PD differences between Japanese and non-Japanese participants. Conclusion A single dose of VIS649, up to 12.0 mg/kg, was safe and well tolerated in healthy adults and was able to suppress free serum APRIL to the lower level of quantification. Serum Gd-IgA1 decreased in parallel with total serum IgA and recovered in a dose-dependent manner following reappearance of free APRIL in serum. These data support the further clinical development of VIS649 as a potential treatment for IgAN.

MO283IMPACT OF VIS649, AN APRIL-NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, ON TETANUS- AND DIPHTHERIA-TOXOID VACCINATION-ELICITED IMMUNE RESPONSES IN HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jonathan Barratt ◽  
Mohit Mathur ◽  
Yusuke Suzuki ◽  
Frank Engler ◽  
Jill Yarbrough ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Intravenous Administration ◽  
Phase 1 ◽  
Study Drug ◽  
Fold Increase ◽  
Antibody Responses ◽  
Diphtheria Toxoid ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Serum Iga

Abstract Background and Aims VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of a proliferation-inducing ligand (APRIL), is in clinical development as a potential treatment for immunoglobulin A (IgA) nephropathy (IgAN). In a Phase 1 study, VIS649 was associated with dose-dependent reductions in serum IgA, IgG and IgM, which were reversible and showed a dose-response effect with respect to time-to-recovery. The aim of the present analysis was to determine if VIS649 suppression of APRIL influences antibody responses to tetanus and diphtheria toxoid vaccination. Method This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study of VIS649 in healthy adult male and female volunteers (ClinicalTrials.gov identifier: NCT03719443). In one cohort within the study, participants were randomized in a 2:1 ratio to receive intravenous administration of VIS649 6.0 mg/kg or placebo, followed by a vaccine composed of tetanus and diphtheria toxoids (TENIVAC®, Sanofi Pasteur Limited), in order to evaluate the effect of VIS649 on recipients’ ability to generate a vaccine booster response (exploratory endpoint). Participants received intravenous administration of study drug on Day 1, were discharged from the institution on Day 2, received a single intramuscular dose of vaccine at the Week 4 visit, and were followed for 16 weeks in total on an outpatient basis. Blood samples were taken at regular intervals, and anti-tetanus toxoid and anti-diphtheria toxoid IgG, IgM and IgA quantitative ELISA assays were performed. Tetanus and diphtheria anti-toxoid IgG titers ≥0.1 IU/mL are generally considered to be protective. Results In the vaccination cohort, 15 participants were randomized and dosed with study drug or placebo, of whom 14 completed the study, and one participant who received VIS649 was lost to follow-up prior to receiving the vaccine. Both groups (placebo and VIS649) demonstrated increased tetanus anti-toxoid IgG titers following immunization, with a mean 7.9-fold increase in IU/mL at Week 6 for placebo recipients and a mean 6.4-fold increase in IU/mL for VIS649 recipients (Figure). At visits after Week 6, tetanus anti-toxoid IgG titers declined faster in the VIS649 group than in the placebo group (consistent with the reduction in total IgG associated with VIS649 administration) but remained above the protective threshold of 0.1 IU/mL for all participants throughout the study. Similar trends were observed for diphtheria anti-toxoid IgG titers, with a mean 5.5-fold increase in IU/mL at the Week 6 visit for placebo recipients and a mean 5.1-fold increase for VIS649 recipients (Figure). There was no evidence of tetanus- or diphtheria-toxoid elicited IgM responses in either the placebo or VIS649 groups, consistent with the recall nature of the vaccination. In a post hoc analysis, pre-existing serum tetanus/diphtheria anti-toxoid IgA titers fell between Day 1 and Week 4 in the VIS649 group, consistent with the overall suppression of total serum IgA, were boosted after vaccination in both groups, and declined faster in the VIS649 recipients thereafter. Conclusion VIS649 treatment did not interfere with participants’ ability to mount an antigen-specific serum IgG or IgA boost response to tetanus and diphtheria toxoid vaccination. There was no evidence of tetanus- or diphtheria-specific IgM responses in either the placebo or VIS649 groups, consistent with recall vaccination exposure. These data indicate that qualitative antibody responses are preserved during APRIL suppression.

scholarly journals A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Virus Monoclonal Antibody, MHAB5553A, in Healthy Volunteers

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Jeremy J. Lim ◽  
Michael A. Derby ◽  
Yaping Zhang ◽  
Rong Deng ◽  
Richard Larouche ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Influenza B Virus ◽  
Influenza B ◽  
Double Blind ◽  
Double Blind Placebo ◽  
B Virus ◽  
Dose Study ◽  
Single Ascending Dose Study ◽  
Dose Proportional

ABSTRACT Influenza B can cause significant morbidity and mortality. MHAB5553A, a human monoclonal immunoglobulin G1 (IgG1) antibody that binds to a highly conserved region of the hemagglutinin protein of influenza B virus, is being examined as a novel therapeutic for the treatment of influenza B patients with severe disease. This phase 1, randomized, double-blind, placebo-controlled, single-ascending-dose study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of MHAB5553A. Twenty-six healthy male and female volunteers of >18 years of age were randomized into five cohorts receiving a single intravenous (i.v.) dose of 120, 1,200, 3,600, 8,400, or 10,800 mg MHAB5553A or placebo (four active:one placebo, except for the 120-mg cohort [4:2]). Subjects were followed for 120 days after dosing. No subject discontinued the study, no dose-limiting adverse events or serious adverse events were reported, and a maximum tolerated dose (MTD) was not defined. The most commonly reported adverse events were cold symptoms and headache; most were mild and occurred at a similar rate across all cohorts. MHAB5553A showed no relevant time- or dose-related changes in laboratory values or vital signs compared to the placebo. The observed serum PK was linear and generally dose proportional, and the observed nasal PK was nonlinear and generally non-dose proportional. MHAB5553A is generally well tolerated in healthy volunteers up to at least a single i.v. dose of 10,800 mg and demonstrated linear serum PK consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (This study has been registered at ClinicalTrials.gov under registration no. NCT02528903.)

scholarly journals Safety, tolerability and pharmacokinetic characterisation of DACRA KBP-042 in healthy male subjects

2021 ◽  
Author(s):  
Kim Henriksen ◽  
Karen Broekhuizen ◽  
Wadim de Boon ◽  
Morten Karsdal ◽  
Asger Bihlet ◽  
...  
Keyword(s):  
Human Study ◽  
Pharmacokinetic Profile ◽  
Healthy Male ◽  
Double Blind ◽  
Linear Pharmacokinetic ◽  
Dose Study ◽  
Dose Levels ◽  
Dose Dependent ◽  
Male Subjects ◽  
Single Ascending Dose Study

There is a need for anti-diabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was 1) to evaluate safety and tolerability; 2) to evaluate pharmacokinetics and 3) to assess indications of receptor engagement of single ascending doses of KBP-042, a Dual Amylin and Calcitonin Receptor Agonists (DACRA) that has shown promising preclinical data, with superior activity in terms of typical amylin-induced responses including reduction of food intake, weight loss and gluco-regulatory capacities. A randomised double-blind placebo-controlled single ascending dose study was performed with six dose levels of KBP-042 (5, 7.5, 10, 20, 20 evening and 40µg) in healthy male adults. KBP-042 or placebo was administered as a single dose after an overnight fast, followed by a standardized lunch after four hours. KBP-042 was associated with dose-dependent complaints of nausea and vomiting, with a lack of tolerability at doses of 20µg and above. Doses of 5 to 40 μg KBP-042 were behaved according to a linear pharmacokinetic profile. Indications of target receptor engagement were observed at the level of glucose control and lowering of bone resorption, compared to placebo. The results of this study showed that doses up to 40 μg were safe, although tolerability was not present at the highest doses. The study confirmed target receptor engagement at the studied doses.

P.165 Double-blind, placebo-controlled phase 1 single ascending dose study of sage-718

2019 ◽  
Vol 29 ◽  
pp. S128
Author(s):  
H. Murck ◽  
J. Paskavitz ◽  
E. Hoffmann ◽  
S. Li ◽  
C. Silber ◽  
...  
Keyword(s):  
Phase 1 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Dose Study ◽  
Single Ascending Dose Study

scholarly journals A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048

2020 ◽  
Vol 71 (10) ◽  
pp. e657-e664 ◽  
Author(s):  
James S McCarthy ◽  
Cristina Donini ◽  
Stephan Chalon ◽  
John Woodford ◽  
Louise Marquart ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Antimalarial Activity ◽  
Phase 1 ◽  
Pharmacodynamic Modeling ◽  
Maximum Effect ◽  
Double Blind ◽  
Dose Study ◽  
Phosphatidylinositol 4 ◽  
Single Ascending Dose Study ◽  
Infection Study

Abstract Background MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics, and antimalarial activity of a tablet formulation of MMV390048. Methods A 2-part, phase 1 trial was conducted in healthy adults. Part 1 was a double-blind, randomized, placebo-controlled, single ascending dose study consisting of 3 cohorts (40, 80, 120 mg MMV390048). Part 2 was an open-label volunteer infection study using the Plasmodium falciparum induced blood-stage malaria model consisting of 2 cohorts (40 mg and 80 mg MMV390048). Results Twenty four subjects were enrolled in part 1 (n = 8 per cohort, randomized 3:1 MMV390048:placebo) and 15 subjects were enrolled in part 2 (40 mg [n = 7] and 80 mg [n = 8] cohorts). One subject was withdrawn from part 2 (80 mg cohort) before dosing and was not included in analyses. No serious or severe adverse events were attributed to MMV390048. The rate of parasite clearance was greater in subjects administered 80 mg compared to those administered 40 mg (clearance half-life 5.5 hours [95% confidence interval {CI}, 5.2–6.0 hours] vs 6.4 hours [95% CI, 6.0–6.9 hours]; P = .005). Pharmacokinetic/pharmacodynamic modeling estimated a minimum inhibitory concentration of 83 ng/mL and a minimal parasiticidal concentration that would achieve 90% of the maximum effect of 238 ng/mL, and predicted that a single 120-mg dose would achieve an adequate clinical and parasitological response with 92% certainty. Conclusions The safety, pharmacokinetics, and pharmacodynamics of MMV390048 support its further development as a partner drug of a single-dose combination therapy for malaria. Clinical Trials Registration NCT02783820 (part 1); NCT02783833 (part 2).

scholarly journals Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study

2020 ◽  
Vol 57 (1) ◽  
pp. 2001451
Author(s):  
Michael R. Loebinger ◽  
Eva Polverino ◽  
James D. Chalmers ◽  
Harm A.W.M. Tiddens ◽  
Herman Goossens ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Study Drug ◽  
Dependent Manner ◽  
Pulmonary Exacerbation ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Once Daily ◽  
Randomised Study ◽  
Dose Dependent ◽  
Inhalation Powder

The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis.This is a phase II, double-blind, randomised study in bronchiectasis patients aged ≥18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively and were followed up for 8 weeks.Overall, 107 patients were randomised to cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the P. aeruginosa sputum density from baseline to day 29 versus placebo in a dose-dependent manner (p≤0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous TIP and 42.9% on cyclical TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of bronchiectasis was the most frequent (37.4%) adverse event. Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to adverse events.Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the P. aeruginosa sputum density in patients with bronchiectasis and chronic P. aeruginosa infection.

scholarly journals A phase 1 study of single and repeat oral doses of GSK3439171A, a highly selective H-PGDS inhibitor, in healthy adult participants

2021 ◽  
Author(s):  
Thomas Haws ◽  
Nilay Thakkar ◽  
Summer Goodson ◽  
Caroline Sychterz ◽  
Nisha George ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Hypersensitivity ◽  
Phase 1 ◽  
Geometric Mean ◽  
Human Study ◽  
Study Drug ◽  
Prostaglandin D2 ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Oral Doses

Aim: Prostaglandin D2 (PGD2) is implicated in the pathophysiology of inflammatory diseases. GSK3439171A is a potent, reversible, and highly selective azetidine urea inhibitor of haematopoietic prostaglandin D synthase (H-PGDS, a key promoter of PGD2 production in several inflammatory cell types). Based on favourable preclinical data, we performed a first-time-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK3439171A, and the effect of food on these parameters. Methods: This was a phase 1, randomized, double-blind, placebo-controlled, dose-escalation study. Single and repeat oral doses of GSK3439171A were administered to healthy males aged 18–65 years. Levels of inflammatory markers including tetranor-prostaglandin D metabolite (tPGDM) were measured in urine samples. Results: Sixty-six participants were enrolled, with 57 receiving GSK3439171A. Single doses (5–180 mg) and repeat once-daily doses (5 and 11 mg for 14 days; 40 mg for 7 days) were administered. Seven participants (12%) had adverse events (AEs) related to study drug, mainly drug hypersensitivity (n=4 [7%]; non-serious, transient skin rash). There were no serious AEs (SAEs) or clinically significant changes in vital signs, electrocardiogram, or laboratory parameters. Dose-proportional increases in Cmax and AUC(0–inf) were observed, and the geometric mean half-life of GSK3439171A was up to 12 hours. Results were similar when GSK3439171A was taken with or without food. No consistent suppression of tPGDM levels was observed. Conclusion: GSK3439171A was well tolerated in healthy participants and there were no SAEs. Selective inhibition of H-PGDS offers therapeutic potential for muscle-related disorders (e.g. Duchenne Muscular Dystrophy) and muscular recovery following injury.

scholarly journals A Single Administration of AZP-3601, a Novel, Long-Acting PTH Analog, Induces a Significant and Sustained Calcemic Response: Preliminary Data From a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A254-A254
Author(s):  
Soraya Allas ◽  
Michel Ovize ◽  
Michael D Culler ◽  
Clarisse Geraul ◽  
Jeroen van de Wetering ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Clinical Symptoms ◽  
Phase 1 ◽  
High Dose ◽  
Single Administration ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Healthy Humans ◽  
Dose Dependent

Abstract Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bind to the R0 conformation of the PTH1 receptor, which results in prolonged signaling responses in vitro and prolonged calcemic responses in animals despite having a short circulating half-life. A Phase 1 double-blind, placebo-controlled, single and multiple ascending dose study is being conducted to evaluate the safety, tolerability and pharmacodynamics of AZP-3601 in healthy adults. Here we report data from the first cohorts of the single ascending dose portion of the study. Sequential cohorts of 4 (cohort 1) to 8 (cohort 2 to 4) healthy male subjects aged 18–60 years, with a body mass index of 19–28 kg/m2, were assigned to receive 5, 10, 20 or 40μg of AZP-3601 or placebo at a ratio of 3:1. The study drug was administered in the morning by subcutaneous injection in the abdominal wall and was well tolerated with no remarkable adverse events. As compared with placebo controls, AZP-3601 treatment produced a clear, dose-dependent increase in mean albumin-adjusted serum calcium values from baseline. The normal physiological diurnal variation of albumin-adjusted serum calcium was gradually attenuated with 5 and 10μg AZP-3601, and was completely eliminated with 20μg. With the dose of 40μg AZP-3601, mean albumin-adjusted serum calcium values were significantly increased but stayed within normal laboratory range and remained elevated through at least 24 hours post-administration. We observed a dose-dependent decrease in mean endogenous serum PTH that was significantly correlated with the concomitant increase in mean serum calcium. These data provide initial evidence of the pharmacodynamic effect of AZP-3601 in healthy humans characterized by a sustained calcemic response for at least 24 hours following a single administration.

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

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S420-S420 ◽  
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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