Nitazoxanide Pharmacokinetic Parameters in Hepatic Impaired Patients

NCT05116826 | Completed Phase 1 FDA Drug

• 1 other identifier: NTZ-121-1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being conducted to evaluate the major Nitazoxanide (NTZ) active metabolite in adult participants with hepatic impairment and healthy adults.

Conditions

Moderate Hepatic Impairment; Severe Hepatic Impairment; Liver Diseases

Keywords

Pharmacokinetics; Healthy Volunteer; Liver Disease; Hepatic Impairment; Antiparasitic; Antiprotozoal

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration time curve (AUC) from time zero to 12h (AUC0-12)

  In participants with moderate and severe hepatic impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 hours post dose

• AUC from time zero to the time of the last quantifiable concentration (AUC0-t)

  In participants with moderate and severe hepatic impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 hours post dose

• Maximum observed plasma concentration (Cmax),

  In participants with moderate and severe hepatic impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 hours post dose

Secondary Outcomes (4)

• Plasma pharmacokinetics: time of the maximum observed plasma concentration (Tmax), apparent plasma terminal elimination half life (t1/2), AUC from time zero to infinity (AUC0-∞), trough concentration (Ctrough) and percentage of extrapolated (%AUCextrap)

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 hours post dose

• Plasma pharmacokinetics: Tmax, AUC0-12, AUC0-t, AUC0-∞, Cmax, t1/2, %AUCextrap and Ctrough.

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 hours post dose

• Urine pharmacokinetics: amount of drug excreted (Ae), cumulative amount of drug excreted (Ae0-t), and renal clearance (CLR)

  Day-1: pre-dose, Day 1: 0-4 h, 4-8 h, 8-12, 12-24 h post-dose; Day 7: 0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h post-dose

• Plasma and urine pharmacokinetics: After the single oral administration of NTZ 500 mg: Cmax, AUC0-12, AUC0-t, AUC0-∞ , Tmax, t1/2, %AUCextrap, Ae0-∞, Ae0-t and CLR.

  Plasma:Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10, 12 h post dose Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24; and 48 h post dose Urine:Day-1: pre-dose, Day 1: 24 hours urine collection post-dose; Day 7: 48 hours urine collection

Study Arms (3)

Healthy Control Match (Normal hepatic function)

EXPERIMENTAL

NTZ 500 mg twice a day for 7 days

Drug: Nitazoxanide

Moderate Child-Pugh B (Moderate hepatic impairment)

EXPERIMENTAL

NTZ 500 mg twice a day for 7 days

Drug: Nitazoxanide

Severe Child-Pugh C (Severe hepatic impairment)

EXPERIMENTAL

NTZ 500 mg twice a day for 7 days

Drug: Nitazoxanide

Interventions

Nitazoxanide DRUG

500 mg Twice Daily for 7 days

Also known as: NTZ

Healthy Control Match (Normal hepatic function); Moderate Child-Pugh B (Moderate hepatic impairment); Severe Child-Pugh C (Severe hepatic impairment)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, between 18 and 75 years of age, inclusive;
• With a minimum body weight of 50 kg and within a BMI range of 18.0 to 40.0 kg/m\^2, inclusive;
• Females participating in this study must be of non-childbearing potential or must be using highly effective contraception for the full duration of the study;
• Negative human immunodeficiency virus antibody screens at Screening;
• Matched to participants with moderate and/or severe hepatic impairment in age (± 10 years), BMI (± 20 percentage) and sex;
• Participants who have chronic (≥ 6 months) moderate or severe hepatic insufficiency (of any etiology) that has been clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to Screening and must also remain stable throughout the Screening period.

You may not qualify if:

• A positive alcohol test result at Check-In Visit;
• A history of alcohol abuse in the prior 2 years;
• Positive urine screen for drugs of abuse at Screening or Check-In;
• Strenuous exercise within 72 hours prior to Check-In Visit;
• Blood donation or loss of blood (excluding volume drawn at screening or menses) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the dosing;
• History of a major surgical procedure within 30 days prior to Screening;
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed. Bariatric surgery will not be allowed;
• Presence or history of malignancy within the prior 3 years, with the exception of treated basal cell or squamous cell carcinoma;
• Poor peripheral venous access;
• Receipt of blood products within 2 months prior to Check-In Visit;
• Significant history or clinical manifestation of any metabolic (including thyroid), allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder;
• Positive serologic test for hepatitis B surface antigen or for hepatitis C virus antibody at Screening;
• Frequent headaches (\> twice a month) and/or migraines, recurrent nausea and/or vomiting, diarrhea;
• Participants with symptomatic hypotension at Screening, whatever the decrease of blood pressure, or asymptomatic postural hypotension;
• History of unstable diabetes mellitus;

Sponsors & Collaborators

• Genfit: lead

Study Sites (2)

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32802, United States

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Carol Addy, MD

  Genfit

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 11, 2021
• Study Start: November 5, 2021
• Primary Completion: April 8, 2022
• Study Completion: April 13, 2022
• Last Updated: October 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)