Dose-finding study of IV nitroglycerin for the treatment of preterm labor using a continual reassessment method

1999 ◽  
Vol 65 (2) ◽  
pp. 200-200
Author(s):  
J TRELUYER ◽  
M SPIRLET ◽  
S CHEVRET ◽  
E REY ◽  
M TOURNAIRE ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Dose Finding ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Finding Study ◽  
Dose Finding Study

A prospective PGx and PK/PD dose-finding study of irinotecan based on UGT1A1*6 and *28 genotyping (UGT0601)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14560-e14560
Author(s):  
T. Esaki ◽  
T. Satoh ◽  
T. Ura ◽  
T. Tsujinaka ◽  
Y. Sasaki ◽  
...  
Keyword(s):  
Initial Dosage ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Hematological Toxicity ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Finding Study ◽  
Dose Finding Study ◽  
Grade 3 ◽  
Dose Limiting Toxicity

e14560 Background: UGT1A1*6 as well as UGT1A1*28 polymorphisms is associated with decreased glucuronidation of SN-38, the active metabolite of irinotecan (CPT-11). Although the maximum tolerated dose (MTD) and the recommended dose (RD) in Hetero was determined 150 mg/m2 (approval dose in Japan), those of Homo were unknown. Methods: Pts received prior chemotherapies except for CPT-11 for metastatic gastrointestinal cancer were enrolled. UGT1A1 polymorphisms were categorized into Wild(*1/*1), Hetero(*1/*28, *1/*6), and Homo(*28/*28, *6/*6, *28/*6). CPT-11 was administered biweekly. Starting doses were 150 mg/m2 in Wild, 100 mg/m2 in Hetero, and 75 mg/m2 in Homo. DLT was defined as grade 4 hematological, or grade 3 non-hematological toxicity. MTD closest to dose-limiting toxicity (DLT) appearance of 30% was guided by the continual reassessment method in the cohort of Hetero and Homo. DLT and pharmacokinetic (PK) sampling was evaluated during the 1st cycle. Results: Eighty-two pts were enrolled from November 2006 to November 2008 (Wild, Hetero, Homo: 41, 20, and 21, respectively). The dose level reached at 150 mg/m2 in Homo. At 150 mg/m2, DLT was observed in six pts of Homo (grade 4 neutropenia, grade 3 diarrhea: 6 and 1, respectively). The probability of DLTs were 22.2% at 125 mg/m2, and 37.4% at 150 mg/m2. The MTD was determined 150 mg/m2 in pts with Homo group. However, the incidences of grade 3/4 neutropenia at 150 mg/m2 during the 1st cycle were 9.8% (4/41), 18.8% (3/16), and 62.5% (10/16) in Wild, Hetero, and Homo, respectively. And the second administration was delayed 7 days or more in most pts in Homo (63% at 150 mg/m2). In one pt of Homo for *28/*28 died of septic shock during the 2nd cycle. SN-38 AUC (0–24h, ng*hr/mL, median) was 239 in Wild, 237 in Hetero, and 410 in Homo. Pts with Homo showed the different trend of PK/PD compared to those with Wild and Hetero. Conclusions: The MTD was 150 mg/m2 in pts with Homo group and the most frequent DLT was grade 4 neutropenia. However, our findings suggest that 150 mg/m2 q2w is difficult to recommend and the initial dosage and administration should be considered carefully for pts with Homo. [Table: see text]

Using the continual reassessment method: Lessons Learned from an EORTC phase I dose finding study

2006 ◽  
Vol 42 (10) ◽  
pp. 1362-1368 ◽  
Author(s):  
Xavier Paoletti ◽  
Benoît Baron ◽  
Patrick Schöffski ◽  
Pierre Fumoleau ◽  
Denis Lacombe ◽  
...  
Keyword(s):  
Phase I ◽  
Lessons Learned ◽  
Dose Finding ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Finding Study ◽  
Dose Finding Study

scholarly journals How to design a dose-finding study using the continual reassessment method

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Graham M. Wheeler ◽  
Adrian P. Mander ◽  
Alun Bedding ◽  
Kristian Brock ◽  
Victoria Cornelius ◽  
...  
Keyword(s):  
Dose Finding ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Finding Study ◽  
Dose Finding Study

scholarly journals Assessing the inter-patient variability in the area under the concentration curve

2019 ◽  
Vol 53 (1) ◽  
pp. 27-44
Author(s):  
M. Iftakhar Alam
Keyword(s):  
Taylor Series Expansion ◽  
Concentration Curve ◽  
Dose Finding ◽  
Model Function ◽  
Optimum Time ◽  
Continual Reassessment ◽  
Finding Study ◽  
Dose Finding Study ◽  
Approximate Variance

In this paper, we check the accuracy of an approximate variance for the area under the concentration curve (AUC). Based on the model function of a random effects model, an analytic expression for the AUC can be obtained. Then an approximate variance for the AUC can be derived after the linearisation of it using the Taylor series expansion. This variance is used in the construction of confidence interval to check the accuracy of the approximation made. We assume that the data on concentration are collected with the advancement of a dose-finding study. Following the allocation of the lowest dose to a cohort of patients, the concentration of drug in the blood samples is measured at the locally D-optimum time points. The successive doses for the cohorts are determined by the popular continual reassessment method. Four PK proles, along with three plausible dose-response scenarios, are investigated through a simulation study. The numerical findings assure the quality of the approximated variance.

scholarly journals Determination of the ED95 of intrathecal hyperbaric prilocaine with sufentanil for scheduled cesarean delivery: A dose-finding study based on the continual reassessment method

2020 ◽  
Author(s):  
Philippe Goffard ◽  
Yoann Vercruysse ◽  
Renaud Leloup ◽  
Jean-François Fils ◽  
Sylvie Chevret ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Cesarean Delivery ◽  
Dose Finding ◽  
Hyperbaric Bupivacaine ◽  
Continual Reassessment ◽  
Blinded Study ◽  
Finding Study ◽  
Elective Cesarean ◽  
Dose Finding Study ◽  
Double Blinded

Abstract BackgroundScheduled cesarean section is routinely performed under spinal anesthesia using hyperbaric bupivacaine. The current study was undertaken to determine the clinically relevant 95% effective dose of intrathecal 2% hyperbaric prilocaine co-administered with sufentanil for scheduled cesarean section, using continual reassessment method.MethodsWe conducted a dose-response, prospective, double-blinded study to determine the ED95 values of intrathecal hyperbaric prilocaine used with 2,5 mcg of sufentanil and 100 mcg of morphine for cesarean delivery. Each parturient enrolled in the study received an intrathecal dose of hyperbaric prilocaine determined by the CRM and the success or failure of the block was assessed as being the primary endpoint.ResultsThe doses given for each cohort varied from 35 to 50 mg of HP, according to the CRM, with a final ED95 lying between 45 and 50 mg of Prilocaine after completion of the 10 cohorts. Few side effects were reported and patients were globally satisfied.ConclusionsThe ED95 of intrathecal hyperbaric prilocaine with sufentanil 2.5 µg and morphine 100 µg for elective cesarean delivery was found to be between 45 and 50 mg. It may be an interesting alternative to other long-lasting local anesthetics in this context.Trial registrationThe study was registered on January 30, 2017 – retrospectively registered – and results posted at the public database clinicaltrials.gov (NCT03036384 – https://clinicaltrials.gov/ct2/show/NCT03036384).

scholarly journals Determination of the ED95 of intrathecal hyperbaric prilocaine with sufentanil for scheduled cesarean delivery: a dose-finding study based on the continual reassessment method

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
P. Goffard ◽  
Y. Vercruysse ◽  
R. Leloup ◽  
J-F Fils ◽  
S. Chevret ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Cesarean Delivery ◽  
Dose Finding ◽  
Hyperbaric Bupivacaine ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Blinded Study ◽  
Finding Study ◽  
Elective Cesarean ◽  
Double Blinded

Abstract Background Scheduled cesarean section is routinely performed under spinal anesthesia using hyperbaric bupivacaine. The current study was undertaken to determine the clinically relevant 95% effective dose of intrathecal 2% hyperbaric prilocaine co-administered with sufentanil for scheduled cesarean section, using continual reassessment method. Methods We conducted a dose-response, prospective, double-blinded study to determine the ED95 values of intrathecal hyperbaric prilocaine used with 2,5 mcg of sufentanil and 100 mcg of morphine for cesarean delivery. Each parturient enrolled in the study received an intrathecal dose of hyperbaric prilocaine determined by the CRM and the success or failure of the block was assessed as being the primary endpoint. Results The doses given for each cohort varied from 35 to 50 mg of HP, according to the CRM, with a final ED95 lying between 45 and 50 mg of Prilocaine after completion of the 10 cohorts. Few side effects were reported and patients were globally satisfied. Conclusions The ED95 of intrathecal hyperbaric prilocaine with sufentanil 2.5 μg and morphine 100 μg for elective cesarean delivery was found to be between 45 and 50 mg. It may be an interesting alternative to other long-lasting local anesthetics in this context. Trial registration The study was registered on January 30, 2017 – retrospectively registered – and results posted at the public database clinicaltrials.gov (NCT03036384).

scholarly journals Determination of the ED95 of intrathecal hyperbaric prilocaine with sufentanil for scheduled cesarean delivery: A dose-finding study based on the continual reassessment method

2020 ◽  
Author(s):  
Philippe Goffard ◽  
Yoann Vercruysse ◽  
Renaud Leloup ◽  
Jean-François Fils ◽  
Sylvie Chevret ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Cesarean Delivery ◽  
Dose Finding ◽  
Hyperbaric Bupivacaine ◽  
Continual Reassessment Method ◽  
Continual Reassessment ◽  
Blinded Study ◽  
Finding Study ◽  
Elective Cesarean ◽  
Double Blinded

Abstract Background – Scheduled cesarean section is routinely performed under spinal anesthesia using hyperbaric bupivacaine. The current study was undertaken to determine the clinically relevant 95% effective dose of intrathecal 2% hyperbaric prilocaine co-administered with sufentanil for scheduled cesarean section, using continual reassessment method.Methods – We conducted a dose-response, prospective, double-blinded study to determine the ED95 values of intrathecal hyperbaric prilocaine used with 2,5 mcg of sufentanil and 100 mcg of morphine for cesarean delivery. Each parturient enrolled in the study received an intrathecal dose of hyperbaric prilocaine determined by the CRM and the success or failure of the block was assessed as being the primary endpoint.Results – The doses given for each cohort varied from 35 to 50 mg of HP, according to the CRM, with a final ED95 lying between 45 and 50 mg of Prilocaine after completion of the 10 cohorts. Few side effects were reported and patients were globally satisfied.Conclusions – The ED95 of intrathecal hyperbaric prilocaine with sufentanil 2.5 μg and morphine 100 μg for elective cesarean delivery was found to be between 45 and 50 mg. It may be an interesting alternative to other long-lasting local anesthetics in this context.Trial registration – The study was registered on January 30, 2017 – retrospectively registered – and results posted at the public database clinicaltrials.gov (NCT03036384 – https://clinicaltrials.gov/ct2/show/NCT03036384).

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