SNPMiner Trials by Shray Alag


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Report for SNP rs1799853

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Pharmacokinetics of Clindamycin and Trimethoprim-sulfamethoxazole in Infants and Children Using PBPK

Developmental changes in physiology during childhood influence drug dosing. Failure to account for these changes leads to improper dosing, which is associated with decreased drug efficacy and safety in children. Population physiologically-based pharmacokinetic (PBPK) modeling offers the opportunity to predict optimal drug dosing based on physiologic parameters adjusted for developmental changes. PBPK models are mathematical constructs that incorporate physiologic processes with drug characteristics and genetic variances to characterize the dose-exposure relationship across the age continuum. These models integrate drug-specific (e.g., metabolism, protein binding) and systems-specific (e.g., organ size, blood flow) information to predict the effect of different factors (e.g., age, genetic variants, disease) on drug exposure. By accounting for these factors and using data from clinical trials to confirm the modeling, PBPK models can reduce the number of children needed for clinical trials while maximizing dose-based efficacy and safety. This trial will evaluate a platform to prospectively validate population PBPK models in children. The study drugs, clindamycin and Bactrim (aka TMP-SMX), are ideal candidates to evaluate population PBPK models in children due to their differing physico-chemical properties and elimination pathways. In addition, a trial of clindamycin and TMP-SMX has broad clinical applicability, as both drugs are among the most commonly used agents to treat gram-positive infections in infants and children.

NCT02475876 Bacterial Infections Drug: Clindamycin Drug: trimethoprim-sulfamethoxazole
MeSH: Bacterial Infections

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Heterozygous for any CYP2C9 Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Homozygous for any CYP3A Family Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Number of Subjects Homozygous for any CYP2C9 Genotype.

Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.. Inclusion Criteria: 1. Informed consent from parent or guardian and assent from subject when appropriate 2. Require prevention or treatment of confirmed or suspected infection 3. PMA >36 weeks 4. Able to take oral drugs (TMP-SMX) 5. Sufficient IV access for study drug administration (for clindamycin) and PK sample collection (both drugs) - Exclusion Criteria: 1. History of allergic reactions to study drugs 2. Treatment with the following drugs within 24 hours prior to first dose of clindamycin or expected to receive these drugs during the treatment phase with clindamycin: - CYP3A4 inhibitors (nefazodone, fluconazole, ketoconazole, fluvoxamine, conivaptan, diltiazem, verapamil, aprepitant, ticlopidine, crizotinib, and imatinib), or - CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, troglitazone, pioglitazone, and St. John's wort).

Primary Outcomes

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Maximum observed plasma concentration at steady state (Cmaxss) - clindamycin

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Area under the plasma concentration versus time curve from the start to the end of one dosing interval at steady state (AUCss) - clindamycin

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Maximum observed plasma concentration at steady state (Cmaxss) - Trimethoprim-Sulfamethoxazole

Time: PK sampling taken during 3 continuous days of treatment

Description: We will use the population PBPK models to simulate drug concentration vs. time data for each individual subject using the characteristics and genetic information of the subjects enrolled in the study. We will compare simulated vs. observed plasma concentrations.

Measure: Area under the plasma concentration versus time curve from the start to the end of one dosing interval at steady state (AUCss) - Trimethoprim-Sulfamethoxazole

Time: PK sampling taken during 3 continuous days of treatment

Secondary Outcomes

Description: Number of AEs and SAEs reported during (3 continuous days) and up to 30 days after study drug administration

Measure: Number of reported AEs and SAEs

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Heterozygous for any CYP3A Family Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Heterozygous for any CYP2C9 Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Homozygous for any CYP3A Family Genotype

Time: 33 days

Description: Genetic analysis of the most important single nucleotide polymorphisms (SNPs) in the CYP3A family and CYP2C9 genes will be performed using commercially available Taqman Polymerase Chain Reactions assays for the following gene expressions: CYP3A4: rs35599367, rs2246709, rs4646437, rs2740565, rs4253728 CYP3A5: rs776746, rs10264272, rs15524 CYP3A7: rs2687133, rs2257401 CYP2C9: rs1799853, rs1057910 Subjects will be classified into homozygous and heterozygotes for allelic variants based on the genotyping results.

Measure: Number of Subjects Homozygous for any CYP2C9 Genotype

Time: 33 days


HPO Nodes