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

NCT06736340 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DC08RUP/1/21
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess the PK and safety of rupatadine (10 mg) and its active metabolites in participants with mild, moderate, or severe hepatic impairment compared to matched control participants with normal hepatic function. The study duration will be up to 38 days, including Screening, Baseline, Study Period, and EOS Visit assessments. Rupatadine 10 mg tablet will be administered as single dose.

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (18)

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

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

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

• Time of maximum plasma concentration (tmax) of rupatadine

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

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

• Apparent total clearance (CL/F) of rupatadine

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

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

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

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

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

• Area under the plasma concentration-time curve from time zero to last time point (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 time point (AUC0-t), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

• Terminal elimination rate constant (kel) 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 elimination rate constant (kel), of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 hepatic impairment in comparison to normal hepatic function (control) participants.

  10 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 of rupatadine metabolites after administration of a single dose of 10 mg in participants with mild, moderate, and severe hepatic impairment in comparison to normal hepatic function (control) participants.

  10 days

Secondary Outcomes (23)

• Area under the plasma concentration-time curve from time zero to last time point (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 (9)

• Relationship between hepatic functional abnormalities (international normalized ratio [INR]), and PK parameters (AUC0-inf) for rupatadine and its metabolites in terms of plasma concentrations

  10 days

• Relationship between hepatic functional abnormalities (international normalized ratio [INR]), and PK parameters (AUC0-t) for rupatadine and its metabolites in terms of plasma concentrations

  10 days

• Relationship between hepatic functional abnormalities (international normalized ratio [INR]), and PK parameters (Cmax) for rupatadine and its metabolites in terms of plasma concentrations

  10 days

Study Arms (4)

Hepatic imparement mild

EXPERIMENTAL

Drug: Rupatadine

Hepatic imparement moderate

EXPERIMENTAL

Drug: Rupatadine

Hepatic imparement severe

EXPERIMENTAL

Drug: Rupatadine

Hepatic normal functions

EXPERIMENTAL

Drug: Rupatadine

Interventions

Rupatadine DRUG

10mg tablets

Also known as: Pafinur

Hepatic imparement mild; Hepatic imparement moderate; Hepatic imparement severe; Hepatic 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 hepatic function and participants with mild, moderate, or severe hepatic 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 subject, 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
• Women of non-childbearing potential (WoNCBP), i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a follicular stimulating hormone \[FSH\] test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis (Section 0 \[Appendix 4\]).

You may not qualify if:

• Participants with normal hepatic function and participants with mild, moderate, or severe hepatic 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.
• 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.
• 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.
• Positive results at Screening from either the hepatitis B or C serology based on hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody (Ig M and total antihepatitis B core antibody), and hepatitis C virus antibody (HCV) markers, except for vaccinated subjects or subjects with past resolved hepatitis.

Sponsors & Collaborators

• Noucor Health S.A.: lead

Study Sites (7)

BlueClinical Phase I

Porto, Porto District, 4250-449, Portugal

Location

Centro Hospitalar De Vila Nova De Gaia Espinho

Gaia, 4434-502, Portugal

Location

Hospital Pedro Hispano

Matosinhos Municipality, 4450-113, Portugal

Location

Municipal Institute Of Medical Investigation

Barcelona, 08003, Spain

Location

Hospital Universitario De La Princesa

Madrid, 28006, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (24)

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  BACKGROUND

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Related Links

• Summary of Product Characteristics (SmPC) for rupatadine

MeSH Terms

Interventions

rupatadine

Study Officials

• Serafim Guimarães, MD

  Blueclinical Investigacao E Desenvolvimento Em Saude Lda.

  PRINCIPAL INVESTIGATOR

• Rosa Maria Príncipe, MD

  Hospital Pedro Hispano

  PRINCIPAL INVESTIGATOR

• Joana Cochicho, 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

• Germán Soriano Pastor, MD

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

  PRINCIPAL INVESTIGATOR

• Alberto Borobia Pérez, MD

  Hospital Universitario La Paz

  PRINCIPAL INVESTIGATOR

• Antonio Portolés Pérez, MD

  Hospital Clinico San Carlos

  PRINCIPAL INVESTIGATOR

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: This is an open-label, non-randomized, parallel group study comparing the PK after administration of a single 10 mg dose of rupatadine to participants with hepatic impairment with matched control participants with normal hepatic function (matched in terms of age, gender, and body weight).

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: December 16, 2024
• Study Start: November 17, 2022
• Primary Completion: April 9, 2025
• Study Completion: April 9, 2025
• Last Updated: May 28, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); PT (3)