Pharmacokinetics and Safety of Rupatadine in Participants With Renal Impairment Compared to Control Participants

NCT06708520 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DC09RUP/1/21
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess the PK, tolerability, and safety of rupatadine (10 mg) and its active metabolites in participants with renal impairment compared to matched control participants with normal renal function. The study duration will be up to 40 days, including Screening, Baseline, Study Period, and EOS visit assessments. Rupatadine 10 mg tablet will be administered as single dose.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (20)

• Area under the plasma concentration-time curve from time zero to last timepoint (AUC0-t) of rupatadine

  To assess the pharmacokinetics (PK), including the area under the plasma concentration-time curve from time zero to last timepoint (AUC0-t), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of rupatadine

  To assess the pharmacokinetics (PK), including the area under the plasma concentration-time curve from time zero to infinity (AUC0-inf), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Peak plasma concentration (Cmax) of rupatadine

  To assess the pharmacokinetics (PK), including the peak plasma concentration (Cmax), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Time of maximum plasma concentration (tmax) of rupatadine

  To assess the pharmacokinetics (PK), including the time of maximum plasma concentration (tmax) of rupatadine, of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Plasma fraction unbound (fu) of rupatadine

  To assess the pharmacokinetics (PK), including the plasma fraction unbound (fu), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Terminal elimination rate constant (kel) of rupatadine

  To assess the pharmacokinetics (PK), including the terminal elimination rate constant (kel), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Terminal half-life (t1/2) of rupatadine

  To assess the pharmacokinetics (PK), including the terminal half-life (t1/2), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Apparent total plasma clearance (CL/F) of rupatadine

  To assess the pharmacokinetics (PK), including the apparent total plasma clearance (CL/F), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Apparent volume of distribution during terminal phase (Vz/F) of rupatadine

  To assess the pharmacokinetics (PK), including the apparent volume of distribution during terminal phase (Vz/F), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Apparent non-renal clearance (CLNR/F) of rupatadine

  To assess the pharmacokinetics (PK), including the apparent non-renal clearance (CLNR/F), calculated as apparent total clearance - renal clearance, of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Renal clearance (CLR) of rupatadine

  To assess the pharmacokinetics (PK), including the renal clearance (CLR), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Amount excreted unchanged (Ae) in urine of rupatadine

  To assess the pharmacokinetics (PK), including the amount excreted unchanged (Ae) in urine, of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Fraction excreted in urine (fe; fe%) of rupatadine

  To assess the pharmacokinetics (PK), including the fraction excreted in urine (fe; fe%), of rupatadine after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Peak plasma concentration (Cmax) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the peak plasma concentration (Cmax) , of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Area under the plasma concentration-time curve from time zero to last timepoint (AUC0-t) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the area under the plasma concentration-time curve from time zero to last timepoint (AUC0-t), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the area under the plasma concentration-time curve from time zero to infinity (AUC0-inf), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Time of maximum plasma concentration (tmax) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the time of maximum plasma concentration (tmax) , of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Terminal half-life (t1/2) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the terminal half-life (t1/2), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Renal clearance (CLR) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the renal clearance (CLR), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

• Metabolic ratio (MR) of metabolites UR-12338, desloratadine (UR-12790), 3-OH desloratadine (UR-12788), 5-OH desloratadine (UR-12767), and 6-OH desloratadine (UR-12766)

  To assess the pharmacokinetics (PK), including the metabolic ratio (MR), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe renal impairment in comparison to participants with normal renal function (control)

  12 days

Secondary Outcomes (15)

• Area under the plasma concentration-time curve from time zero to last timepoint (AUC0-t) of unbound (free) rupatadine

  1 day

• Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of unbound (free) rupatadine

  1 day

• Peak plasma concentration (Cmax) of unbound (free) rupatadine

  1 day

• Time of maximum plasma concentration (tmax) of unbound (free) rupatadine

  1 day

• Terminal elimination rate constant (kel) of unbound (free) rupatadine

  1 day

Other Outcomes (1)

• The relationship between renal function (estimated glomerular filtration rate [eGFR] using modification of diet in renal disease equation) and PK parameters (AUC0-t and Cmax) for rupatadine and its metabolites in terms of plasma concentrations

  12 days

Study Arms (4)

Renal impairement mild

EXPERIMENTAL

Drug: Rupatadine

Renal impairement moderate

EXPERIMENTAL

Drug: Rupatadine

Renal impairement severe

EXPERIMENTAL

Drug: Rupatadine

Renal normal functions

EXPERIMENTAL

Drug: Rupatadine

Interventions

Rupatadine DRUG

10 mg tablets

Also known as: Pafinur

Renal impairement mild; Renal impairement moderate; Renal impairement severe; Renal normal functions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with normal renal function and participants with mild, moderate, or severe renal impairment who meet the following criteria will be considered eligible to participate in the clinical study:
• Participant understands the study procedures and agrees to participate in the study by giving written informed consent prior to any study-mandated procedure.
• Able to communicate well with the Investigator, to understand and comply with the study requirements.
• Willing to comply with study restrictions stated in Section 5.3 (lifestyle considerations).
• Male or female Caucasian subjects, between 18 and 75 years (inclusive) of age.
• Body mass index (BMI) is between 18 to 35 kg/m2 at Screening.
• Women of childbearing potential (WoCBP) must have a negative serum pregnancy test at Screening, a negative urine pregnancy test on Day -1, and agree to consistently and correctly use (from 30 days prior to dosing, during the entire study, and for at least 30 days after dosing), a highly effective method of contraception (i.e., failure rate of \< 1%) (Section 10.4 \[Appendix 4\]). Such methods include:
• \- Hormonal contraceptives: combined (estrogen- and progesterone-containing) contraception associated with inhibition of ovulation using oral, intravaginal, or transdermal route of administration.
• Note: If a hormonal contraceptive is used, it must be initiated at least 30 days before dosing.
• Intrauterine device.
• Intrauterine hormone-releasing system.
• Bilateral tubal occlusion.
• Vasectomized partner, provided that the partner is the sole sexual partner and that the vasectomized partner has received medical assessment of the surgical success.
• Sexual abstinence, defined as refraining from heterosexual intercourse from 30 days prior to dosing up to at least 30 days after dosing, if this is the preferred and usual lifestyle of the subject.
• WoCBP must also agree not to donate ova from the time of informed consent until 30 days after dosing

You may not qualify if:

• Participants with normal renal function and participants with mild, moderate, or severe renal impairment who meet one or more of the following criteria will not be considered eligible to participate in the clinical study:
• Pregnant or lactating women.
• Participant is unlikely to comply with the protocol requirements, instructions and study related restrictions; e.g., uncooperative attitude, inability to return for the EOS Visit and improbability of completing the clinical study.
• Any psychological, emotional problems, any disorders or resultant therapy that is likely to invalidate informed consent, or limit the ability of the participant to comply with the protocol requirements
• History of hypersensitivity to rupatadine, desloratadine or any of the excipients, or to medicinal products with similar chemical structures.
• History of clinically significant lactose, galactose, or fructose intolerance.
• Any clinically relevant acute or chronic disease which could jeopardize the safety of the participant or impact the validity of the study results.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
• Participation in another clinical trial with an experimental drug within 2 months or 5 halflives (whichever is longer) before the Screening or in more than 2 clinical studies within 1 year prior to Screening.
• History or presence of clinically significant angioedema.
• Use of caffeine-containing beverages exceeding 800 mg per day (Section 5.3.2) at Screening.
• Nicotine consumption (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) from 48 h prior to Baseline (Day -1) until discharge from confinement (Day 2).
• Positive test result for urine alcohol and drugs of abuse (amphetamines, benzodiazepines, cannabinoids, cocaine and opiates) at Screening and Baseline.
• Note: Subjects receiving stable treatment of methadone and benzodiazepines will be allowed to be enrolled in the study even if the urine drug screen test is positive.
• History of heart, kidney or liver transplantation.

Sponsors & Collaborators

• Noucor Health S.A.: lead

Study Sites (7)

Centro Hospitalar De Vila Nova De Gaia Espinho

Gaia, 4434-502, Portugal

RECRUITING

Hospital Pedro Hispano

Matosinhos Municipality, 4450-113, Portugal

RECRUITING

Blueclinical Investigacao E Desenvolvimento Em Saude Lda.

Porto, 4250-449, Portugal

RECRUITING

Hospital Universitari Germans Trias I Pujol

Badalona, 8916, Spain

RECRUITING

Municipal Institute Of Medical Investigation

Barcelona, 08003, Spain

RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, 08025, Spain

RECRUITING

Hospital Universitario De La Princesa

Madrid, 28006, Spain

RECRUITING

Related Publications (22)

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• Eiser NM, Mills J, Snashall PD, Guz A. The role of histamine receptors in asthma. Clin Sci (Lond). 1981 Apr;60(4):363-70. doi: 10.1042/cs0600363.

  PMID: 7249528 BACKGROUND

• Cuss FM, Dixon CM, Barnes PJ. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189-92. doi: 10.1016/s0140-6736(86)92489-x.

  PMID: 2873440 BACKGROUND

• Henocq E, Vargaftig BB. Accumulation of eosinophils in response to intracutaneous PAF-acether and allergens in man. Lancet. 1986 Jun 14;1(8494):1378-9. doi: 10.1016/s0140-6736(86)91683-1. No abstract available.

  PMID: 2872485 BACKGROUND

• Piwinski JJ, Wong JK, Green MJ, Ganguly AK, Billah MM, West RE Jr, Kreutner W. Dual antagonists of platelet activating factor and histamine. Identification of structural requirements for dual activity of N-Acyl-4-(5,6-dihydro-11H-benzo [5,6]cyclohepta-[1,2-b]pyridin-11-ylidene)piperidines. J Med Chem. 1991 Jan;34(1):457-61. doi: 10.1021/jm00105a069. No abstract available.

  PMID: 1671420 BACKGROUND

• Prescott SM, Zimmerman GA, McIntyre TM. The production of platelet-activating factor by cultured human endothelial cells: Regulation and function. In Platelet-activating factor and related lipid mediators. Snyder F, Ed. New York: Plenum Press, 1987: 323-340.

  BACKGROUND

• Katiyar S, Prakash S. Pharmacological profile, efficacy and safety of rupatadine in allergic rhinitis. Prim Care Respir J. 2009 Jun;18(2):57-68. doi: 10.3132/pcrj.2008.00043.

  PMID: 18695846 BACKGROUND

• Mullol J, Bousquet J, Bachert C, Canonica WG, Gimenez-Arnau A, Kowalski ML, Marti-Guadano E, Maurer M, Picado C, Scadding G, Van Cauwenberge P. Rupatadine in allergic rhinitis and chronic urticaria. Allergy. 2008 Apr;63 Suppl 87:5-28. doi: 10.1111/j.1398-9995.2008.01640.x.

  PMID: 18339040 BACKGROUND

• Queralt M, Brazis P, Merlos M, de Mora F, Puigdemont A. In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1. Inflamm Res. 2000 Jul;49(7):355-60. doi: 10.1007/PL00000216.

  PMID: 10959557 BACKGROUND

• Merlos M, Ramis I, Balsa D, Queralt M, Brazís P, Puigdemont A. Inhibitory effect of rupatadine on TNF-a release from human monocytes and mast cell lineHMC-1. J.Allergy Clin. Immunol. 2000 105(Suppl.1): S62.

  BACKGROUND

• Bartra J, Valero AL, del Cuvillo A, Davila I, Jauregui I, Montoro J, Mullol J, Sastre J. Interactions of the H1 antihistamines. J Investig Allergol Clin Immunol. 2006;16 Suppl 1:29-36. No abstract available.

  PMID: 17357375 BACKGROUND

• del Cuvillo A, Mullol J, Bartra J, Davila I, Jauregui I, Montoro J, Sastre J, Valero AL. Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol. 2006;16 Suppl 1:3-12. No abstract available.

  PMID: 17357372 BACKGROUND

• Olkkola KT, Ahonen J. Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16.

  PMID: 18175099 BACKGROUND

• Picado C. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders. Expert Opin Pharmacother. 2006 Oct;7(14):1989-2001. doi: 10.1517/14656566.7.14.1989.

  PMID: 17020424 BACKGROUND

• Izquierdo I, Merlos M, Garcia-Rafanell J. Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis. Drugs Today (Barc). 2003 Jun;39(6):451-68. doi: 10.1358/dot.2003.39.6.799450.

  PMID: 12944997 BACKGROUND

• Keam SJ, Plosker GL. Rupatadine: a review of its use in the management of allergic disorders. Drugs. 2007;67(3):457-74. doi: 10.2165/00003495-200767030-00008.

  PMID: 17335300 BACKGROUND

• European Medicines Agency. Committee for Medicinal Products for Human Use Guidance: Guideline on the Investigation of Drug Interactions. 21 June 2012.

  BACKGROUND

• Rupatadine Investigator's Brochure, dated 21 Sep 2021.

  BACKGROUND

• Food and Drug Administration Guidance: Pharmacokinetics in Patients with Impaired Renal Function: Study Design, Data Analysis, and Impact on Dosing . September 2020.

  BACKGROUND

• European Medicines Agency. Committee for Medicinal Products for Human Use Guidance: Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function. December 2015.

  BACKGROUND

• FDA Guidance: Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency-Guidance for Industry, Investigators, and Institutional Review Boards: August 2021.

  BACKGROUND

• DMID ALCOAC Checklist V2.0 29 January 2020.

  BACKGROUND

Related Links

• Summary of Product Characteristics (SmPC) for rupatadine

MeSH Terms

Conditions

Renal Insufficiency

Interventions

rupatadine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Serafim Guimarães

  Blueclinical Investigacao E Desenvolvimento Em Saude Lda.

  PRINCIPAL INVESTIGATOR

• Rosa Maria Príncipe, MD

  Hospital Pedro Hispano

  PRINCIPAL INVESTIGATOR

• Daniela Machado Lopes, MD

  Centro Hospitalar de Vila Nova de Gaia/Espinho

  PRINCIPAL INVESTIGATOR

• Dolores Ochoa Mazarro, MD

  Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

  PRINCIPAL INVESTIGATOR

• Ana Maria Aldea Perona, MD

  Municipal Institute Of Medical Investigation

  PRINCIPAL INVESTIGATOR

• Jordi Soler Majoral, MD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

• Rosa Maria Antonijoan Arbós, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Peris, PharmD

CONTACT

+34937376690; daniel.peris@noucor.com

Laia Casas, MSc

CONTACT

+34937376690; laia.casas@noucor.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1, single dose, open-label, parallel group

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: November 27, 2024
• Study Start: November 21, 2022
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: May 28, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3); ES (4)