scholarly journals Comparative Efficacies of Terbinafine and Fluconazole in Treatment of Experimental Coccidioidal Meningitis in a Rabbit Model

2000 ◽  
Vol 44 (11) ◽  
pp. 3087-3091 ◽  
Author(s):  
Kevin N. Sorensen ◽  
Raymond A. Sobel ◽  
Karl V. Clemons ◽  
Leilani Calderon ◽  
Kimberley J. Howell ◽  
...  
Keyword(s):  
Oral Treatment ◽  
White Male ◽  
Rabbit Model ◽  
Coccidioides Immitis ◽  
Survival Times ◽  
Slight Effect ◽  
Once Daily ◽  
Glucose Levels ◽  
Polyethylene Glycol 200 ◽  
Leukocyte Counts

ABSTRACT A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of terbinafine (TBF) and fluconazole (FCZ). Hydrocortisone acetate-treated New Zealand White male rabbits were infected intracisternally with either 2.2 × 104 or 6.4 × 104 Coccidioides immitisarthroconidia. Oral treatment with polyethylene glycol 200 (PEG) twice daily (n = 8), TBF twice daily (n = 9; 200 mg/kg of body weight/day), or FCZ once daily (n= 8; 80 mg/kg/day) began on day 5 and continued for 21 days. Mean survival times were 20, 24, and 32 days for rabbits treated with PEG, TBF, and FCZ, respectively. All of the FCZ-treated animals (100%;P = 0.003), 56% of the TBF-treated animals (P = 0.4), and 25% of the PEG-treated animals survived the length of the study. Both FCZ and TBF were effective at reducing the incidence of paresis. Only FCZ was effective at reducing most neurological and systemic signs. FCZ treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of CSF fungal cultures compared with those for PEG-treated controls, but TBF treatments had no significant effect on these parameters. Neither drug affected CSF glucose levels. Mean serum TBF levels by bioassay were within the range of 3.5 to 6.2 μg/ml at 1, 2, and 4 h postdosing and 0.35 to 7.0 μg/ml at 14 h postdosing. No TBF was detected in CSF. Mean FCZ levels (24 to 25.5 h postdosing) by bioassay were 16.4 to 19.2 and 13.5 to 19.2 μg/ml in serum and CSF, respectively. The reduction in the numbers of CFU in the spinal cord and brain was over 100-fold (P= 0.0005) in FCZ-treated animals and 2-fold (P ≤ 0.2) in TBF-treated animals compared with those in PEG-treated animals. Histopathologic severity (semiquantitative scoring system) was significantly attenuated by FCZ treatment (P = 0.05) and was slightly attenuated by TBF treatment compared with that for the controls. In conclusion, TBF appeared to have a slight effect on survival, histology, and reduction of the numbers of CFU in tissue; however, these effects were not significant. FCZ was effective at controlling coccidioidal meningitis.

scholarly journals Comparison of Fluconazole and Itraconazole in a Rabbit Model of Coccidioidal Meningitis

2000 ◽  
Vol 44 (6) ◽  
pp. 1512-1517 ◽  
Author(s):  
Kevin N. Sorensen ◽  
Raymond A. Sobel ◽  
Karl V. Clemons ◽  
Demosthenes Pappagianis ◽  
David A. Stevens ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Rabbit Model ◽  
Term Therapy ◽  
Coccidioides Immitis ◽  
Treatment Groups ◽  
Glucose Levels ◽  
Polyethylene Glycol 200 ◽  
Leukocyte Counts ◽  
Long Term Therapy

ABSTRACT Coccidioidal meningitis is a devastating disease that requires long-term therapy with little hope of cure. A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of fluconazole (FCZ) and itraconazole (ITZ). Hydrocortisone-treated male New Zealand white rabbits were infected intracisternally with 5.0 × 104 to 5.4 × 104arthroconidia of Coccidioides immitis. Oral treatment with polyethylene glycol 200 (PEG) (n = 9), FCZ (n = 8; 80 mg/kg of body weight/day), or ITZ (n = 8; 80 mg/kg/day) began 5 days after infection and continued for 28 consecutive days. Both FCZ and ITZ reduced the number of CFU of C. immitis organisms in the spinal cord and brain compared with the number in PEG-treated animals (P ≤ 0.003), but the results for FCZ and ITZ were not different from each other. Histopathologic severity (semiquantitative scoring system by an observer blinded to treatment) was equally reduced in both FCZ and ITZ treatment groups compared with that in controls (P ≤ 0.0004). Both treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing ofC. immitis from CSF compared with the results for PEG-treated controls. Neither drug affected CSF glucose levels. Both compounds were effective at reducing neurological and systemic signs and extending survival (P ≤ 0.014). FCZ was more effective at reducing head and body shakes, posture changes, and incontinence; ITZ was more effective at reducing continuous fever. Mean levels of FCZ and ITZ in the serum and CSF were determined by bioassay; at 17 to 26 h postdosing, levels were 28.1 to 40.0 and 22.4 to 29.9 μg/ml, respectively, for FCZ and 0.77 to 2.51 and 0 μg/ml, respectively, for ITZ. The sera of most animals developed antibody toC. immitis, but azole treatment attenuated antibody development in CSF and its titer. In conclusion, both FCZ and ITZ were efficacious, but neither was curative in a rabbit model of coccidioidal meningitis.

scholarly journals Pharmacokinetics and pharmacodynamics of ampreloxetine, a novel, selective norepinephrine reuptake inhibitor, in symptomatic neurogenic orthostatic hypotension

2021 ◽  
Author(s):  
Arthur Lo ◽  
Lucy Norcliffe-Kaufmann ◽  
Ross Vickery ◽  
David Bourdet ◽  
Jitendra Kanodia
Keyword(s):  
Orthostatic Hypotension ◽  
Sympathetic Neurons ◽  
Oral Treatment ◽  
Plasma Concentrations ◽  
Treatment Phase ◽  
Target Population ◽  
Neurogenic Orthostatic Hypotension ◽  
Open Label ◽  
Once Daily ◽  
Norepinephrine Reuptake

Abstract Purpose Ampreloxetine is a novel, selective, long-acting norepinephrine reuptake (NET) inhibitor being investigated as a once-daily oral treatment for symptomatic neurogenic orthostatic hypotension (nOH) in patients with autonomic synucleinopathies. The purpose of this study was to characterize the pharmacokinetic and pharmacodynamic profiles of ampreloxetine in this target population. Methods Patients with nOH were enrolled in a multicenter, phase II clinical trial of ampreloxetine (NCT02705755). They received escalating doses over 5 days in the clinical research unit, followed by 20 weeks of open-label treatment and then a 4-week withdrawal. As neurochemical biomarkers of NET inhibition, we assayed plasma concentrations of norepinephrine (NE) and its main intraneuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) pre- and post-ampreloxetine. Results Thirty-four patients with nOH were enrolled. Plasma ampreloxetine concentrations increased with repeated escalating doses, with peak concentrations observed 6–9 h post-drug administration. The median ampreloxetine dose in the 20-week treatment phase was 10 mg once daily. Plasma ampreloxetine concentrations reached steady state by 2 weeks, with stable plasma levels over 24 h. No influence of age or renal function on ampreloxetine plasma concentrations was observed. On treatment, compared to baseline, plasma NE significantly increased by 71% (p < 0.005), plasma DHPG significantly declined by 22% (p < 0.05), and the NE:DHPG ratio significantly increased (p < 0.001). Conclusions Persistent elevation of plasma NE levels accompanied by reduced DHPG levels after ampreloxetine suggests reduced neuronal reuptake and metabolism of NE in postganglionic efferent sympathetic neurons. The findings are consistent with long-lasting NET inhibition, which may increase vasoconstrictor tone, supporting once-daily ampreloxetine dosing in patients with nOH.

scholarly journals Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Takumi Isaka ◽  
Hiroko Otake ◽  
Yosuke Nakazawa ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Plasma Glucose ◽  
Polyacrylic Acid ◽  
Rabbit Model ◽  
Postprandial Hyperglycemia ◽  
Postprandial Blood Glucose ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Protamine Zinc Insulin ◽  
Bead Mill

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.

scholarly journals 168. Efficacy of the Novel gwt1 Inhibitor APX2039 in a Rabbit Model of cryptococcus Meningitis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S213-S213
Author(s):  
Karen J Shaw ◽  
Charles D Giamberardino ◽  
Quinlyn A Soltow ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Oral Treatment ◽  
Treatment Options ◽  
Rabbit Model ◽  
Experimental Period ◽  
Control Group ◽  
Log10 Reduction ◽  
Research Support ◽  
Rapid Reduction ◽  
Geographical Regions

Abstract Background Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. New oral treatment options are needed that demonstrate rapid reductions in CFU in CSF and brain tissue. APX2039 is a novel inhibitor of the fungal Gwt1 enzyme, which catalyzes an early step in glycosylphosphatidyl inositol (GPI) anchor biosynthesis. It is highly active against both C. neoformans and C. gattii and has previously demonstrated significant efficacy in a mouse delayed-treatment model of CM. CSF Fungal Burden in Rabbits Methods Male New Zealand White rabbits were inoculated with C. neoformans H99 (1.4 ×106 CFU) directly into the cisterna magna. Rabbits were immunosuppressed with cortisone acetate at 7.5 mg/kg (i.m.), starting on Day -1 relative to inoculation and then administered drug daily throughout the 14-day experimental period. Treatment was initiated on Day 2 postinfection and continued through Day 14 consisting of: 50 mg/kg APX2039 PO (BID), 80 mg/kg fluconazole (FLU) PO (QD), c) 1 mg/kg amphotericin B deoxycholate (AMB) IV (QD); and vehicle control. CSF was removed via an intracisternal tap on Days 2, 7, 10 and 14 post-infection and CFU/ml was assessed. Animals were sacrificed on Day 14 and CFU/g brain tissue was assessed. Results APX2039 demonstrated rapid reduction in CFU in both CSF and brain tissue. The range in CFU values in rabbit CSF is shown (Figure). Reductions in CFU were statistically different from the control group for all treatment groups. APX2039 was also different from both FLU and AMB and resulted in sterilization in CSF by Day 10. Brain harvested on Day 14 demonstrated a reduction in CFU/g tissue vs control of 1.8 log10 and 3.4 log10 for FLU and AMB, respectively, while a &gt; 6 log10 reduction (tissue sterilization) was observed for APX2039. Conclusion APX2039 demonstrated potent efficacy in a rabbit model of CM. The more rapid clearance in CSF than either AMB or FLU, as well as &gt; 6 log10 reduction in brain CFU highlights the unique properties of this drug, warranting further investigation of this molecule for the treatment of CM. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Charles D. Giamberardino, Jr., MR, Box (Shareholder) John R. Perfect, MD, amplyx (Grant/Research Support)astellas (Grant/Research Support)astellas (Grant/Research Support)

Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study

2017 ◽  
Vol 19 (12) ◽  
pp. 1302-1306 ◽  
Author(s):  
Linda Toresson ◽  
Joerg M Steiner ◽  
Gunilla Olmedal ◽  
MajBritt Larsen ◽  
Jan S Suchodolski ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Gastrointestinal Disease ◽  
Oral Treatment ◽  
Clinical Signs ◽  
Reference Interval ◽  
Inclusion Criteria ◽  
Promising Alternative ◽  
Once Daily ◽  
Oral Supplementation ◽  
Number Of Patients

Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214–738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27–94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111–250 pmol/l) prior to treatment and 2701 pmol/l (738–16,359 pmol/l) after supplementation. This difference was statistically significant ( P <0.0001). Conclusions and relevance Our results suggest that oral cobalamin supplementation is effective in increasing serum cobalamin to supranormal concentrations in cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

scholarly journals Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study

2020 ◽  
Author(s):  
Austin G Stack ◽  
David Han ◽  
Ronald Goldwater ◽  
Susanne Johansson ◽  
Nalina Dronamraju ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Oxidase Inhibitor ◽  
Renal Tubules ◽  
Clinical Trial Registration ◽  
Xanthine Oxidase Inhibitor ◽  
Once Daily ◽  
Glucose Levels ◽  
Safety Parameters ◽  
Excretion Rates

Abstract Context Combining a sodium-glucose cotransporter 2 inhibitor with a xanthine oxidase inhibitor (XOI) and a urate transporter 1 (URAT1) inhibitor may enhance serum uric acid (sUA) lowering. However, concerns exist regarding high urinary UA (uUA) excretion rates and subsequent crystallization in renal tubules. Objective To assess whether dapagliflozin added to verinurad, a selective URAT1 inhibitor, and febuxostat, an XOI, increases uUA excretion. Design Randomized, placebo-controlled, 2-way crossover study (NCT03316131). Patients Adults with asymptomatic hyperuricemia. Interventions Subjects (N = 36) were randomized to oral once-daily 9 mg verinurad plus 80 mg febuxostat plus 10 mg dapagliflozin for 7 days and 7 days of oral once-daily 9 mg verinurad plus 80 mg febuxostat plus placebo with an intervening 7- to 21-day washout period. Main Outcome Measure Difference in peak uUA excretion between groups from baseline to day 7. Secondary outcomes included changes in sUA levels and 24-h uUA excretion. Results Both regimens lowered mean peak uUA excretion (least squares mean changes from baseline: −12.9 mg/h [95% confidence interval (CI): −21.0 to −4.7], dapagliflozin; −13.2 mg/h [95% CI −21.3 to –5.0], placebo). sUA concentrations were lower with dapagliflozin (mean treatment difference –62.3 µmol/L [95% CI −82.8 to −41.8]). Dapagliflozin did not impact verinurad pharmacokinetics, its main metabolites, or febuxostat or fasting plasma glucose levels vs verinurad plus febuxostat. There were no clinically relevant changes in safety parameters. Conclusions Dapagliflozin further reduced sUA without influencing uUA excretion, suggesting that its combination with verinurad and febuxostat at the doses tested does not adversely affect kidney function. Clinical trial registration number NCT03316131.

Low-dose oral administration of human interferon alpha can control the development of Theileria parva infection in cattle

Parasitology ◽  
1990 ◽  
Vol 101 (2) ◽  
pp. 201-209 ◽  
Author(s):  
A. S. Young ◽  
A. C. Maritim ◽  
D. P. Kariuki ◽  
D. A. Stagg ◽  
J. M. Wafula ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Oral Treatment ◽  
Human Interferon ◽  
Theileria Parva ◽  
Once Daily ◽  
Treatment Groups ◽  
Control Calf ◽  
Dose Oral ◽  
Homologous Challenge

Two natural human interferon alpha preparations, (nHuIFN-μ [Cantell]) and (Nhuifn-μ [ISI]), were used for the oral treatment of cattle experimentally infected with Theileria parva parva. In the first experiment, 8 Friesian bulls were inoculated with a 1 in 10 dilution of a sporozoite stabilate of T. p. parva (Marikebuni) stock. Four of the cattle were treated daily with 1 international unit/kg body weight (i.u./kg bwt) of nHuIFN-μ (Cantell) from day –2 to day 8 p.i. None of the 4 calves given IFN developed clinical theileriosis, but 3 of the 4 control calves died of theileriosis while the fourth had a mild infection. Three of 4 treated calves and the 1 surviving control calf developed a detectable antibody response to T. p. parva schizont antigen but, on challenged with a 10-fold higher dose of stabilate, the surviving control animal and only 1 of the 4 treated calves proved to be immune. In a second experiment, 4 groups of 4 calves were inoculated with the same stabilate dilution. Three treatment groups were given either 1 i.u. nHuIFN-μ (Cantell), 1 i.u. nHuIFN-μ (ISI), or 10 i.u. nHuIFN-μ (ISI)/kg bwt from day –2 to day 8 p.i. once daily and the fourth group were controls. Clinical theileriosis occurred in 2 controls, 2 calves given 10 i.u. nHuINF-μ (ISI), 1 calf given 1 i.u. nHuIFN-μ (ISI) and no calves given 1 i.u. nHuIFN-μ (Cantell)/kg bwt. Of these, 2, 1, 0 and 0 cattle died in the respective groups. All the surviving cattle proved to be immune on homologous challenge with 10-fold higher dose of stabilate except the 2 cattle which did not develop high antibody responses. A third experiment using an undiluted challenge of T. p. parva (Muguga) sporozoite stabilate (10α) on 8 steers. Four steers were treated with 1 i.u. nHuIFN-α (Cantell)/kg bwt and 4 were controls. All calves developed acute theileriosis and the experiment was terminated. Cells of the C2 lymphoblastoid cell line, infected with T. p. parva (Muguga) schizonts, were cultured in vitro with various concentrations (0-01-100 i.u./ml) of nHuIFN-a (Cantell). The IFN appeared to have no effect on host cell or parasite developmental variables when compared to untreated control cultures.

Growth Stimulation and Biochemical Changes in Juvenile Coho Salmon (Oncorhynchus kisutch) Exposed to Bleached Kraft Pulpmill Effluent for 200 Days

1974 ◽  
Vol 31 (6) ◽  
pp. 1043-1049 ◽  
Author(s):  
D. J. McLeay ◽  
D. A. Brown
Keyword(s):  
Prolonged Exposure ◽  
Coho Salmon ◽  
Growth Stimulation ◽  
Total Blood ◽  
Body Protein ◽  
Glucose Levels ◽  
Acid Ratio ◽  
Kraft Mill Effluent ◽  
Leukocyte Counts ◽  
Resistance To Stress

Juvenile coho salmon were exposed for 200 days to neutralized, filtered bleached kraft mill effluent (BKME) at concentrations of 0.1 and 0.25 of the samples' 96-h LC50 values. From 50 to 200 days, mean weights of fish exposed to 0.25 LC50 BKME were significantly higher than control values; those of fish in 0.1 LC50 BKME were consistently but not significantly higher than control weights. By 200 days, mean weight of fish receiving the higher BKME concentration was twice that of controls. Length and condition factor of this group of fish were also increased. Growth results are considered in terms of BKME-induced behavioral changes, increased nutrient supply, effluent salinity, hormetic effects, and hormonal changes.Lactate levels were elevated in the blood and muscle of coho fry exposed to the higher BKME concentration only; serum pyruvate levels were decreased in fish receiving either concentration. The serum lactic acid:pyruvic acid ratio was increased in both groups of fish continuously exposed to BKME. It was concluded that these fish had developed an oxygen debt.Plasma glucose levels were elevated in BKME-exposed fish. The liver muscle glycogen ratio was increased in fish held in 0.1 or 0.25 LC50 BKME for 200 days. Body moisture and lipid content were not altered by prolonged exposure to BKME. Body protein content was decreased in those exposed to 0.25 LC50 effluent. Total blood cell, erythrocyte, leukocyte–thrombocyte and differential leukocyte counts were not altered. Numbers of circulating neutrophils were increased by the higher effluent concentration.The chronic stress response pattern displayed was similar to a previously proposed stage of resistance to stress for mammals.

FOENIX-101: A phase II trial of TAS-120 in patients with intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS468-TPS468 ◽  
Author(s):  
Lipika Goyal ◽  
Rastilav Bahleda ◽  
Junji Furuse ◽  
Juan W. Valle ◽  
Markus Hermann Moehler ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Intrahepatic Cholangiocarcinoma ◽  
Oral Treatment ◽  
Objective Response ◽  
Gene Rearrangements ◽  
Tumor Type ◽  
Once Daily ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy

TPS468 Background: Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from the intrahepatic bile duct. Standard treatment of unresectable, recurrent, or metastatic iCCA is with cytotoxic chemotherapy. FGFR2 gene fusions have been identified as oncogenic drivers in 10–20% of iCCA tumors, but no targeted agents have been established to date. TAS-120 is an investigational irreversible FGFR1–4 inhibitor in development as a once-daily oral treatment for iCCA. Based on initial studies in multiple tumor types expressing FGFR abnormalities, iCCA was identified as a tumor type with potential susceptibility to FGFR inhibition and high unmet need. A phase I portion of the trial with an iCCA expansion cohort demonstrated tolerability and preliminary evidence of clinical efficacy with TAS-120 as a continuous, once-daily oral treatment in patients with iCCA. The most common AEs in the phase I portion of the trial were hyperphosphatemia, a mechanism-based on-target side effect, cutaneous AEs, and gastrointestinal AEs. The phase I portion of the study is continuing to enroll, and final results are anticipated in early 2019. Based on preliminary findings, a phase II portion of the study (FOENIX-101; clinicaltrials.gov registration NCT02052778) has been initiated. Methods: The phase II portion of the trial is a global, single-arm study of TAS-120 in patients with iCCA harboring FGFR2 gene rearrangements. The study will enroll approximately 100 adult patients with locally advanced or metastatic iCCA that progressed after ≥ 1 systemic therapies and with an ECOG PS of 0 or 1. Prior systemic therapy must include gemcitabine plus platinum-based chemotherapy. Screening for FGFR2 gene rearrangements will be performed at a central laboratory. The primary endpoint is objective response rate based on RECIST v1.1. Secondary endpoints include duration of response, disease control rate, overall survival, progression-free survival, safety, and health-related quality of life. Clinical trial information: NCT02052778.

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