P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD)

Abstract Background Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on E. coli and other Enterobacteriaceae in patients with CD. In a previous study, sibofimloc up to 1500 mg twice daily was well tolerated when administered to healthy subjects over a 14-day period. PK results indicated that sibofimloc was detectable in plasma at a very low level. The current study investigated the PK, safety, and pharmacodynamic effects of sibofimloc following 13 days of 1500 mg twice daily oral administration in patients with CD. Objectives of this study were to determine the PK (primary) and safety profiles, effects on inflammatory biomarkers, gut microbiome and on stool frequency and pain score. Methods We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period. Results Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table. In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml. Conclusion These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.

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Single-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites Alone and in Combination with Gemfibrozil, Itraconazole, or Rifampin in Healthy Subjects: A Randomized, Parallel-Group, Open-Label Study

Advances in Therapy ◽

10.1007/s12325-020-01473-0 ◽

2020 ◽

Vol 37 (10) ◽

pp. 4381-4395

Author(s):

Jonathan Q. Tran ◽

Peijin Zhang ◽

Atalanta Ghosh ◽

Liangang Liu ◽

Mary Syto ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Active Metabolites ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Parallel Group

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Pharmacokinetics and dopamine d2 and serotonin 5-ht2a receptor occupancy of paliperidone in healthy subjects: two open-label, single-dose studies (PAL-115)

Pharmacopsychiatry ◽

10.1055/s-2007-991781 ◽

2007 ◽

Vol 40 (05) ◽

Cited By ~ 5

Author(s):

P Karlsson ◽

L Hargarter ◽

E Dencker ◽

S Nyberg ◽

E Mannaert ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Receptor Occupancy ◽

Open Label ◽

Dopamine D2

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Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Metabolites ◽

10.3390/metabo11050276 ◽

2021 ◽

Vol 11 (5) ◽

pp. 276

Author(s):

Stefania Raimondo ◽

Dragana Nikolic ◽

Alice Conigliaro ◽

Gianluca Giavaresi ◽

Bruna Lo Sasso ◽

...

Keyword(s):

Risk Factors ◽

Healthy Subjects ◽

Cardiometabolic Risk ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Modifiable Risk Factors ◽

Low Density Lipoprotein Cholesterol ◽

Open Label ◽

Open Label Study ◽

Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

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An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function

Clinical Pharmacology in Drug Development ◽

10.1002/cpdd.149 ◽

2014 ◽

Vol 4 (4) ◽

pp. 256-261 ◽

Cited By ~ 6

Author(s):

Franklin K. Johnson ◽

Paul N. Mudd ◽

Tara DiMino ◽

Jennie Vosk ◽

Sheela Sitaraman ◽

...

Keyword(s):

Renal Function ◽

Normal Renal Function ◽

Healthy Subjects ◽

Impaired Renal Function ◽

Open Label ◽

Open Label Study ◽

Label Study

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Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00008-07 ◽

2007 ◽

Vol 51 (8) ◽

pp. 2982-2984 ◽

Cited By ~ 4

Author(s):

Mary B. Wire ◽

Charles H. Ballow ◽

Julie Borland ◽

Mark J. Shelton ◽

Yu Lou ◽

...

Keyword(s):

Steady State ◽

Healthy Subjects ◽

Open Label ◽

Time Curve ◽

Once Daily ◽

Open Label Study ◽

Label Study ◽

Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

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