Effect of Genetic Polymorphisms of UGT on the PKs of Indapamide in Egyptians

NCT05294484 | Unknown Phase 4

• 1 other identifier: PG/PK Study on Indapamide
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this works is to investigate the effect of genetic variation of UGT2B7 on human response to treatment with indapamide and its correlation with pharmacokinetic parameters in Egyptian subjects.

Conditions

Pharmacogenomics

Outcome Measures

Primary Outcomes (7)

• the PK parameters of Indapamide following single oral dose include:

  area under the concentration-time curve over the dosing interval (AUC\[0-tau\])

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• maximum concentration (Cmax)

  maximum concentration (Cmax)

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• time of occurrence of Cmax (Tmax)

  time of occurrence of Cmax (Tmax)

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• terminal phase half-life (T1/2)

  terminal phase half-life (T1/2)

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• clearance

  clearance

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• volume of distribution

  volume of distribution

  at Day 0: prior to drug administration (blank), then samples (5ml each) will be obtained at 0.5 hour, 1 hour, 1.5 hour, 2 hour, 2.5 hour, 3 hour, 4 hour, 5 hour, 6 hour, 8 hour, 10 hour, 12 hour, and 24 hour after drug administration

• Detection of UGT2B7 SNPs (rs 7438135, rs 11740316) (genetic variation in Egyptian population)

  Samples will be collected from each subject into tubes and stored at -80°C, Genomics DNA will be isolated according to manufactures instructions. Polymorphisms will be assessed using suitable recommended assay.

  6 months

Secondary Outcomes (3)

• Vital sign measurement following single dose administration as a measure of safety and tolerability

  every month up to 6 months

• pulse rate

  up to 6 months

• body temperature

  up to 6-7 months

Study Arms (2)

Fasting group

ACTIVE COMPARATOR

Following an overnight fast of at least 10 hours, subjects should be administered single dose of indapamide 1.5 mg SR with 240 mL (8 fluid ounces) of water. No food should be allowed for at least 4 hours post-dose. Water can be allowed as desired except for one hour before and after drug administration. Subjects should receive standardized meals scheduled at the same time in each period of the study.

Drug: Indapamide 1.5 MG SR

Fed group

ACTIVE COMPARATOR

Following an overnight fast of at least 10 hours, subjects should start the recommended meal 30 minutes prior to administration of the drug. Study subjects should eat this meal in 30 minutes or less; however, indapamide 1.5 mg SR should be administered 30 minutes after start of the meal. The drug should be administered with 240 mL (8 fluid ounces) of water. No food should be allowed for at least 4 hours post-dose. Water can be allowed as desired except for one hour before and after drug administration. Subjects should receive standardized meals scheduled at the same time in each period of the study. All subjects should abstain from the consumption of fruit juices during the study period. All the subjects are to be under complete medical supervision.

Drug: Indapamide 1.5 MG SR

Interventions

Indapamide 1.5 MG SR DRUG

the effect of genetic variation of UGT2B7 on human response to treatment with indapamide and its correlation with pharmacokinetic parameters in Egyptian subjects

Fasting group; Fed group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects should be healthy adult volunteers with age between (18-45) with normal body weight.
• The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests (hematology, clinical chemistry, urinalysis, serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody)

You may not qualify if:

• Treatment with any known enzyme -inducing /inhibiting agent within 30 days prior to the start of the study and throughout the study.
• Subjects who have taken any medication less than two weeks of the trials starting date
• Susceptibility to allergic reaction to study drugs
• Any prior surgery of the gastrointestinal tract that may interfere with drug absorption
• Gastrointestinal diseases
• Renal diseases
• Pancreatic disease including diabetes
• Hepatic diseases
• Hematological diseases or pulmonary diseases
• Abnormal laboratory values
• Subject who have donated blood or who have been involved in multiple dosing study requiring a large volume of blood (more than 500 ml) to be drawn within 6 weeks preceding the start of the study.

Sponsors & Collaborators

• Ain Shams University: lead

Related Publications (4)

• Reilly RF, Peixoto AJ, Desir GV. The evidence-based use of thiazide diuretics in hypertension and nephrolithiasis. Clin J Am Soc Nephrol. 2010 Oct;5(10):1893-903. doi: 10.2215/CJN.04670510. Epub 2010 Aug 26.

  PMID: 20798254 BACKGROUND

• Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR, Lemaitre RN, Wagner EH, Furberg CD. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA. 1997 Mar 5;277(9):739-45.

  PMID: 9042847 BACKGROUND

• Campbell DB, Phillips EM. Short term effects and urinary excretion of the new diuretic, indapamide, in normal subjects. Eur J Clin Pharmacol. 1974 Oct 4;7(6):407-14. doi: 10.1007/BF00560352. No abstract available.

  PMID: 4612998 BACKGROUND

• Wang TH, Hsiong CH, Ho HT, Shih TY, Yen SJ, Wang HH, Wu JY, Kuo BP, Chen YT, Ho ST, Hu OY. Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects. AAPS J. 2014 Mar;16(2):206-13. doi: 10.1208/s12248-013-9535-x. Epub 2013 Dec 20.

  PMID: 24357089 BACKGROUND

MeSH Terms

Interventions

Indapamide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Nagwa A. Sabri, professor

  Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University

  STUDY CHAIR

Central Study Contacts

Amal A Elkholy, PhD

CONTACT

+201060355448; amalanas9@gmail.com

Banaz D Abbas, Master

CONTACT

01206053991; Banazdara2017@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A comparative randomized, single-dose, two-treatment (fed vs. fasting), parallel design of indapamide in healthy adult Egyptions

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: March 24, 2022
• Study Start: March 15, 2022
• Primary Completion: July 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 24, 2022

Record last verified: 2021-12