Non-interaction Study of Chlorthalidone and Losartan in Fixed Combination, in Healthy Subjects, Under Fasting Conditions

NCT ID: NCT05090449

Last Updated: 2021-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-01

Study Completion Date

2020-05-25

Brief Summary

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Monocentric study of no pharmacokinetic interaction between chlorthalidone and losartan, with an open, randomized, single-dose design with four periods, four sequences and crossover in healthy volunteers, under fasting conditions, administered in fixed combination (Test product of Laboratorios Silanes, SA de CV) against the individual components administered jointly and separately (Higroton® 50, a product of Sandoz, SA de CV and Cozaar® , a product of Schering-Plow, SA de CV)

Detailed Description

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The study was designed to recruit 36 healthy subjects, which were randomized for this study contemplating losses. All the volunteers whose data allowed at least one comparison to be made were included in the corresponding statistical analysis. The objective was to statistically compare the bioavailability of chlorthalidone (at normalized dose) and losartan potassium, in a non-interaction pharmacokinetic study after single-dose oral administration of a product with the fixed combination of active ingredients with respect to the individual components administered together and separately in healthy fasting volunteers. As a secondary objective, the tolerability of the presentations was evaluated based on the registry of adverse events at the end of the four study periods.

Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A1: Individual formulation of chlorthalidone

(Higroton 50, product of Sandoz, S.A. de C.V.)

Group Type ACTIVE_COMPARATOR

Chlorthalidone (HIGROTON® 50)

Intervention Type DRUG

Tablets with 50mg of Chlorthalidone, product de Sandoz, S.A. de C.V.

A2:Individual formulation Losartan

(COZAAR, product of Schering Plough, S.A. de C.V., S.A. de C.V.)

Group Type ACTIVE_COMPARATOR

Losartan (COZZAR®)

Intervention Type DRUG

Losartan potassium 100 mg tablet, a product of Schering-Plough, S.A. C.V.

A3: Co-administration of individual formulations

Co-administration of individual formulations of chlorthalidone and losartan potassium

Group Type ACTIVE_COMPARATOR

A1+ A2 Co-administration of Chlorthalidone and Losartan

Intervention Type DRUG

50mg chlorthalidone + 100 mg losartan potassium

B: Fixed combination of chlorthalidone and losartan potassium

B: Fixed combination of chlorthalidone and losartan potassium (product of Laboratorios Silanes S.A. de C.V.)

Group Type EXPERIMENTAL

Chlorthalidone + Losartan Fixed-Dose combination

Intervention Type DRUG

Tablets with fixed combination of Chlorthalidone 25 mg and Losartan Potassium

Interventions

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Chlorthalidone (HIGROTON® 50)

Tablets with 50mg of Chlorthalidone, product de Sandoz, S.A. de C.V.

Intervention Type DRUG

Losartan (COZZAR®)

Losartan potassium 100 mg tablet, a product of Schering-Plough, S.A. C.V.

Intervention Type DRUG

A1+ A2 Co-administration of Chlorthalidone and Losartan

50mg chlorthalidone + 100 mg losartan potassium

Intervention Type DRUG

Chlorthalidone + Losartan Fixed-Dose combination

Tablets with fixed combination of Chlorthalidone 25 mg and Losartan Potassium

Intervention Type DRUG

Other Intervention Names

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Chlo Los Chlo + Los FDC

Eligibility Criteria

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Inclusion Criteria

* The participation of the subjects was voluntarily in accordance with the guidelines proposed in the General Health Law and their consent will be obtained according to the aforementioned law. Likewise, the standards set by the Declaration of Helsinki, the Brazilian Review and Good Clinical Practices will be maintained.
* Only healthy male volunteers between 18 and 55 years of age were included. - The body mass index of the subjects should be between 18.0-27.0 kg / m2 according to Quetelet.
* The volunteers must be healthy, a criterion determined by the results of a complete medical history carried out by the doctors of the Clinical Research site and the laboratory and clinical test (12-lead electrocardiogram) carried out by a certified Clinical Laboratory and / or staff of the Center.
* The limits of variation allowed within normality in the screening visit was: blood pressure (sitting) from 90 to 129 mm Hg systolic and 60 to 79 mm Hg diastolic, heart rate between 50 and 100 beats per minute and respiratory rate between 14 and 20 breaths per minute according to current SOP with code CLI-DES-008 "Measurement of Vital Signs". Vital signs will be taken after 5 minutes of resting in a sitting position.
* Subjects willing to practice abstinence as a lifestyle or use of two family planning methods (including barrier methods, non-hormonal intrauterine device or bilateral tubal obstruction, and hysterectomy) during the course of the clinical study and up to 30 days after the last dose.
* The laboratory and test examinations that will be carried out for the inclusion of the subjects during the selection visit to the study will be:

1. Complete hematic biometry with differential count: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, distribution width of erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
2. 27-element blood chemistry: glucose, urea, BUN, creatinine, BUN / creatinine ratio, uric acid, cholesterol, HDL cholesterol, triglyperides, LDL cholesterol, Non-HDL cholesterol, atherogenic index, total proteins, albumin, globulins, A / ratio G, total bilirubin, direct bilirubin, indirect bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), alkaline phostatase, gamma-glutamyltraspeptidase, LDH, iron, calcium, sodium, potassium, and chlorine.
3. General urine test. Physical examination (color, appearance, density); chemical examination (pH, leukocytes, nitrites, proteins, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysmorphic erythrocytes, casts, crystals, pavement cells, renal tubular cells, mucoid networks, bacteria, yeast).
4. Hepatitis B and C serum tests: HBV surface antigen and anti-HCV Antibody.
5. HIV serum tests: Anti-HIV \[Human immunodeficiency virus\] 1 and 2 antibodies.
6. VDRL \[Venereal Disease Research Laboratory\] serum test.
7. Urine drug abuse tests (qualitative) at screening visit and approximately 12 hours prior to each drug administration.
8. Inline alcohol detection test approximately 12 hours before each drug administration.
9. 12-lead electrocardiogram, which will be taken after 5 minutes of rest in the upright position.

Exclusion Criteria

* Volunteers with a history of cardiovascular, kidney, liver, lung, muscle, metabolic, gastrointestinal, neurological, endocrine, hematopoietic, mental illness or other organic abnormalities. As well as those who have had a muscle trauma within the 21 days prior to the start of the study.
* Volunteers requiring any medication during the course of the study, other than the medication being studied. - Volunteers with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer. - Volunteers who have been exposed to drugs known as liver enzyme inducers or inhibitors or who have taken potentially toxic drugs within the 30 days prior to the start of the study.
* Volunteers who have received any medication, including vitamins (with or without a prescription) or herbal remedies 30 days (or 7 half-lives) prior to the start of the study. - Clinically significant abnormalities in the electrocardiographic trace. - Electrolyte disturbances: hypokalemia, hyponatremia, hypercalcemia, and symptomatic hyperuricemia.
* Volunteers who have been hospitalized for any problem during the six months prior to the start of the study.
* Subjects who received investigational drugs within 90 days (3 months) prior to the study. - Subjects allergic to study drugs: chlorthalidone and sulphonamide derivatives, as well as losartan.
* Subjects who have ingested alcohol and / or carbonated beverages and / or containing xanthines (coffee, tea, cocoa, chocolate, mate, cola soft drinks) or who have ingested charcoal-grilled food or grapefruit juice within the previous 10 hours at the beginning of each hospitalization period or subjects who smoked tobacco within 10 hours prior to the start of the study.
* Subjects who have donated or lost 450 mL or more of blood within the 60 days prior to the start of the study.
* Subjects with a history of drug abuse and / or alcoholism.
* Volunteers who require a special diet for any reason or are on a different diet, for example vegetarian.
* Incapacity of any kind that makes it impossible for the volunteer to understand the nature, objective and possible consequences of the study.
* Evidence of non-cooperative attitude during the development of the study.
* Volunteers with positive urine drug abuse test or breath alcohol test.
* Volunteers who are not registered on the COFEPRIS page.
* Relationship of subordination between research subjects and researchers.
* Employees of the Sponsor and / or IFaB.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Laboratorios Silanes S.A. de C.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Araceli G Medina Nolasco, M.D

Role: PRINCIPAL_INVESTIGATOR

Investigación Farmacológica y Biofarmacéutica, S.A.P.I. de C.V.

Liz J Medina Reyes, M.D

Role: PRINCIPAL_INVESTIGATOR

Investigación Farmacológica y Biofarmacéutica, S.A.P.I. de C.V.

Locations

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Laboratorio Silanes, S.A. de C.V.

Mexico City, , Mexico

Site Status

Countries

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Mexico

References

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Bienert A, Brzeziniski R, Szalek E, Dubai V, Grzeskowiak E, Dyderski S, Drobnik L, Wolc A, Olejniczak-Rabinek M. Bioequivalence study of two losartan formulations administered orally in healthy male volunteers. Arzneimittelforschung. 2006;56(11):723-8. doi: 10.1055/s-0031-1296781.

Reference Type BACKGROUND
PMID: 17220048 (View on PubMed)

Das AK, Dhanure S, Savalia AK, Nayak SK, Tripathy SK. Human bioequivalence evaluation of two losartan potassium tablets under fasting conditions. Indian J Pharm Sci. 2015 Mar-Apr;77(2):190-5. doi: 10.4103/0250-474x.156583.

Reference Type BACKGROUND
PMID: 26009652 (View on PubMed)

del Castillo D, Campistol JM, Guirado L, Capdevilla L, Martinez JG, Pereira P, Bravo J, Perez R. Efficacy and safety of losartan in the treatment of hypertension in renal transplant recipients. Kidney Int Suppl. 1998 Dec;68:S135-9. doi: 10.1046/j.1523-1755.1998.06827.x.

Reference Type BACKGROUND
PMID: 9839298 (View on PubMed)

Dudkowski C, Karim A, Munsaka M. Effects of Food Intake on the Pharmacokinetics of Azilsartan Medoxomil and Chlorthalidone Alone and in Fixed-Dose Combination in Healthy Adults. Clin Pharmacol Drug Dev. 2016 Sep;5(5):393-8. doi: 10.1002/cpdd.249. Epub 2016 Mar 4.

Reference Type BACKGROUND
PMID: 27514506 (View on PubMed)

Mann R, Mackay F, Pearce G, Freemantle S, Wilton L. Losartan: a study of pharmacovigilance data on 14,522 patients. J Hum Hypertens. 1999 Aug;13(8):551-7. doi: 10.1038/sj.jhh.1000880.

Reference Type BACKGROUND
PMID: 10455478 (View on PubMed)

Pentikis HS, Henderson JD, Tran NL, Ludden TM. Bioequivalence: individual and population compartmental modeling compared to the noncompartmental approach. Pharm Res. 1996 Jul;13(7):1116-21. doi: 10.1023/a:1016083429903.

Reference Type BACKGROUND
PMID: 8842055 (View on PubMed)

Potvin D, DiLiberti CE, Hauck WW, Parr AF, Schuirmann DJ, Smith RA. Sequential design approaches for bioequivalence studies with crossover designs. Pharm Stat. 2008 Oct-Dec;7(4):245-62. doi: 10.1002/pst.294.

Reference Type BACKGROUND
PMID: 17710740 (View on PubMed)

Shah JV, Patel DP, Shah PA, Sanyal M, Shrivastav PS. Simultaneous quantification of atenolol and chlorthalidone in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Biomed Chromatogr. 2016 Feb;30(2):208-16. doi: 10.1002/bmc.3537. Epub 2015 Jul 7.

Reference Type BACKGROUND
PMID: 26096961 (View on PubMed)

Zandbergen AA, Baggen MG, Lamberts SW, Bootsma AH, de Zeeuw D, Ouwendijk RJ. Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial. Ann Intern Med. 2003 Jul 15;139(2):90-6. doi: 10.7326/0003-4819-139-2-200307150-00008.

Reference Type BACKGROUND
PMID: 12859158 (View on PubMed)

Other Identifiers

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CLRLSR-32-SIL

Identifier Type: -

Identifier Source: org_study_id