Dolutegravir Pediatric Liquid Formulation Study

2019 ◽  
Author(s):  
Keyword(s):  
Liquid Formulation

(203) Manufacturing Process for a Highly Purified, Stable Liquid Formulation of Botulinum Toxin Type B (Myobloctm)

Pain Medicine ◽  
2001 ◽  
Vol 2 (3) ◽  
pp. 239-239
Author(s):  
Andrew Grethlein ◽  
Naina Patel ◽  
Jenny Chung ◽  
Bob Dias ◽  
James Callaway
Keyword(s):  
Botulinum Toxin ◽  
Manufacturing Process ◽  
Botulinum Toxin Type ◽  
Type B ◽  
Liquid Formulation ◽  
Botulinum Toxin Type B

scholarly journals Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 849
Author(s):  
Manasa Tatipalli ◽  
Vijay Kumar Siripuram ◽  
Tao Long ◽  
Diana Shuster ◽  
Galina Bernstein ◽  
...  
Keyword(s):  
Pharmacokinetic Model ◽  
Allometric Scaling ◽  
Pediatric Patients ◽  
Reference Product ◽  
Population Pharmacokinetic ◽  
Liquid Formulation ◽  
Sampling Schemes ◽  
Quantitative Pharmacology ◽  
Using Data ◽  
Drug Pharmacokinetics

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.

scholarly journals CTNI-15. CLINICAL EFFICACY OF ONC201 IN NEWLY DIAGNOSED DIPG AND IN PREVIOUSLY IRRADIATED PEDIATRIC H3 K27M-MUTANT GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii45-ii45
Author(s):  
Sharon Gardner ◽  
Carl Koschmann ◽  
Rohinton S Tarapore ◽  
Jeffrey Allen ◽  
Wafik Zaky ◽  
...  
Keyword(s):  
Body Weight ◽  
Single Agent ◽  
Biologically Active ◽  
Pharmacokinetic Analysis ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Liquid Formulation ◽  
Phase Ii Trials ◽  
Body Weights ◽  
Post Radiation

Abstract ONC201, an anti-cancer DRD2 antagonist and ClpP agonist, is in Phase II trials for adult H3 K27M-mutant diffuse midline gliomas. In adults, the recommended phase 2 dose (RP2D) of 625mg ONC201 once a week has been established as a biologically active dose that is well tolerated. Radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. This multi-arm, dose-escalation and dose-expansion trial determined the pediatric RP2D of ONC201 administered as an oral capsule (Arm A) or liquid formulation (Arm E) in post-radiation H3 K27M-mutant glioma (Arm A) or in newly diagnosed DIPG (Arm B) patients. Molecular assessments include intratumoral ONC201 concentrations (Arm C) and CSF H3 K27M DNA levels (Arm D). Enrollment as of April 30, 2020 is complete in Arm A (22) and Arm E (26) and continues in Arm B (18/24), Arm C (5/12), and Arm D (22/24). The RP2D of weekly 625mg ONC201 scaled by body weight was confirmed when administered as a capsule or a liquid formulation as a single agent or in combination with radiation without dose-limiting toxicity. The most frequent adverse events regardless of attribution to the drug were predominantly low grade: ONC201 capsule alone was headache (54.5%), nausea (36.4%), and fatigue (36.4%); ONC201 liquid formulation was vomiting (31.8%), headache (22.7%), VIth nerve disorder (22.7%); ONC201 capsules in combination with radiation (Arm B) was headache (47.1%), vomiting (52.9%), nausea (41.2%). Pharmacokinetic analysis in plasma of Arm A patients revealed T1/2: 8.4h; Tmax: 2.1h; Cmax: 2.3ug/mL; AUC0-tlast: 16.4ug/mL, with similar exposure across body weights. In conclusion, when scaled by body weight the ONC201 capsule or liquid formulation alone or in combination with radiation were associated with safety and pharmacokinetic profiles in pediatric H3 K27M-mutant diffuse midline glioma patients that are similar to the experience in adults.

Enzymatic Synthesis of Eugenyl Acetate from Essential Oil of Clove Using Lipases in Liquid Formulation as Biocatalyst

2021 ◽  
Author(s):  
Leandro Santolin ◽  
Karina G. Fiametti ◽  
Viviane da Silva Lobo ◽  
João H. C. Wancura ◽  
J. Vladimir Oliveira
Keyword(s):  
Essential Oil ◽  
Enzymatic Synthesis ◽  
Liquid Formulation ◽  
Eugenyl Acetate

P1935Pharmacokinetic and pharmacodynamic assessment of a lipid-based aspirin formulation: results of a prospective, randomised, crossover study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D J Angiolillo ◽  
D L Bhatt ◽  
F Lanza ◽  
B Cryer ◽  
J Dong ◽  
...  
Keyword(s):  
Crossover Study ◽  
Safety Profile ◽  
Immediate Release ◽  
Mucosal Injury ◽  
Thromboxane B2 ◽  
Phospholipid Bilayer ◽  
Liquid Formulation ◽  
Parameter Ratio ◽  
Serum Thromboxane ◽  
Parameter Values

Abstract Objectives Aspirin, or acetylsalicylic acid (ASA), can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer, underscoring the need for ASA formulations with a more favorable safety profile while maintaining an effective pharmacologic profile. A liquid formulation using a novel pharmaceutical lipid aspirin complex (PL-ASA) has been designed to prevent the disruption of the protective mucosal bilayer. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with traditional, immediate release aspirin (IR-ASA). Methods In this active-control crossover study, 16 healthy volunteers were randomized to receive a single dose of either IR-ASA 325 mg or PL-ASA 325 mg in a sequential fashion with a 2-week washout period between treatment assignments. The primary objectives of the study were to assess PK (i.e., plasma salicylic acid levels) and PD (i.e., serum thromboxane B2 levels) bioequivalence over a 24–hour period after drug administration, of PL-ASA and IR-ASA using established criteria. Results The PK parameter values were similar for PL-ASA and IR-ASA, with median AUC 0-t and Cmax values nominally higher for PL-ASA. Log-transformed PK parameters meeting FDA-criteria for bioequivalence (80% to 125%) are provided in the Table. Serum thromboxane B2 levels were similar for PL-ASA and IR-ASA, with Cmin values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) for both drugs. Both drugs also showed >99% inhibition of serum thromboxane B2 levels (≥95% inhibition represents the cut-off to define aspirin responders). Several secondary PK/PD parameters showed similarities between the two drugs (data not shown). Overall, these findings support functional and clinical equivalence between PL-ASA and IR-ASA. PK Results Parameter Ratio (PL-ASA/IR-ASA) 90% Confidence Interval AUC0-t 96.51 89.24, 104.37 Cmax 103.73 92.06, 116.89 Conclusions PL-ASA's novel liquid formulation has similar PK and PD performance compared with IR-ASA. The improved endoscopic safety profile of PL-ASA coupled with its pharmacologic efficacy equivalent to IR-ASA may result in an improved benefit-risk performance, warranting evaluation in future trials. Acknowledgement/Funding PLx Pharma, Inc.

scholarly journals DIPG-52. PHASE I CLINICAL TRIAL OF ONC201 IN PEDIATRIC H3 K27M-MUTANT GLIOMA OR NEWLY DIAGNOSED DIPG

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii297-iii297
Author(s):  
Sharon Gardner ◽  
Rohinton Tarapore ◽  
Jeffrey Allen ◽  
Wafik Zaky ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Phase I ◽  
Single Agent ◽  
High Grade Glioma ◽  
Newly Diagnosed ◽  
Liquid Formulation ◽  
Open Label ◽  
Dismal Prognosis ◽  
Expansion Cohort

Abstract H3 K27M-mutant gliomas often manifest as midline gliomas, have a dismal prognosis, and have no effective treatments. ONC201 efficacy has been shown in high-grade glioma preclinical models and durable responses with single agent ONC201 have been reported in adults with recurrent H3 K27M-mutant gliomas. These observations led to a Phase I pediatric clinical trial of ONC201 dosed by body weight. This multi-center, open-label, 3 + 3 dose-escalation and dose-expansion clinical trial (NCT03416530) for H3 K27M-mutant glioma or non-biopsied DIPG has 6 arms: arms A and E determine the RP2D in pediatric post-radiation (recurrent or not-recurrent) H3 K27M-mutant glioma patients with ONC201 administered as an oral capsule as well as a liquid formulation, respectively. Both arms have completed accrual. The study is currently enrolling newly diagnosed DIPG patients to determine the RP2D for ONC201 in combination with radiation (arm B). Dedicated assessment of intratumoral ONC201 concentrations in midline gliomas patients (arm C) and the effects of ONC201 in H3K27M DNA levels in circulating CSF (arm D) are currently enrolling patients. ONC201 as a single agent in patients with progressive H3K27M mutant tumors following irradiation (excluding DIPG/spinal cord tumors) was recently opened (arm F). Once the RP2D is confirmed, there is a dose-expansion cohort to confirm the safety, radiographic efficacy and survival with ONC201. The primary endpoints of arms A, B, and E have been established with the RP2D of 625mg scaled by body weight as a capsule or liquid formulation administered alone or in combination with radiation without incidence of dose-limiting toxicity.

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