Nitazoxanide Pharmacokinetic Parameters in Renal Impaired Subjects

NCT05368935 | Completed Phase 1 FDA Drug

• 1 other identifier: NTZ-122-1
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Renal Impairment; Renal Disease; Kidney Disease

Keywords

Pharmacokinetics; Healthy Volunteer; Renal Disease; Kidney Disease; Renal Impairment; Antiparasitic; Antiprotozoal

Outcome Measures

Primary Outcomes (3)

• Maximum observed plasma concentration (Cmax)

  Plasma pharmacokinetic (PK) parameters of NTZ active metabolite expressed in terms of unbound as well as total concentrations at steady-state in subjects with mild, moderate and severe renal impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24 hours (Day 8); 48 hours (Day 9); 72 hours (Day 10) and 96 hours (Day 11) post-dose

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

  Plasma pharmacokinetic parameters of NTZ active metabolite expressed in terms of unbound as well as total concentrations at steady-state in subjects with mild, moderate and severe renal impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24 (Day 8); 48 (Day 9); 72 (Day 10) and 96 (Day 11) hours post-dose

• AUC from time zero to 12h (AUC0-12)

  Plasma pharmacokinetic parameters of NTZ active metabolite expressed in terms of unbound as well as total concentrations at steady-state in subjects with mild, moderate and severe renal impairment compared to healthy volunteers

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18; 24 hours (Day 8); 48 hours (Day 9); 72 hours (Day 10) and 96 hours (Day 11) post-dose

Secondary Outcomes (25)

• Time of the maximum observed plasma concentration (Tmax) for NTZ and its major active metabolite

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18 hours; 24 hours (Day 8); 48 hours (Day 9) ; 72 hours (Day 10) and 96 hours (Day 11) post-dose

• Apparent plasma terminal elimination half-life (t1/2) for the NTZ and its major active metabolite

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18 hours; 24 hours (Day 8); 48 hours (Day 9) ; 72 hours (Day 10) and 96 hours (Day 11) post-dose

• Unbound fraction in plasma defined as total concentration/unbound concentration (fu) for the NTZ and its major active metabolite

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18 hours; 24 hours (Day 8); 48 hours (Day 9) ; 72 hours (Day 10) and 96 hours (Day 11) post-dose

• Area under the plasma concentration-time curve from time zero to infinity (extrapolated) (AUC0-∞) for the NTZ and its major active metabolite

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18 hours; 24 hours (Day 8); 48 hours (Day 9) ; 72 hours (Day 10) and 96 hours (Day 11) post-dose

• Trough concentration (Ctrough) for the NTZ and its major active metabolite

  Day 1: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10 and 12 hours post dose; Day 2-6: pre-dose; Day 7: pre-dose; 1; 2; 3; 4; 5; 6; 7; 8; 10; 12; 14; 16; 18 hours; 24 hours (Day 8); 48 hours (Day 9) ; 72 hours (Day 10) and 96 hours (Day 11) post-dose

Study Arms (4)

Healthy Control Match (RF ≥ 90 mL/min)

EXPERIMENTAL

500 mg Twice Daily for 7 days

Drug: Nitazoxanide

Mild Renal Impairment (RF ≥ 60 to < 90 mL/min)

EXPERIMENTAL

500 mg Twice Daily for 7 days

Drug: Nitazoxanide

Moderate Renal Impairment (RF ≥ 30 to < 60 mL/min)

EXPERIMENTAL

500 mg Twice Daily for 7 days

Drug: Nitazoxanide

Severe Renal Impairment (RF < 30 mL/min and not on dialysis)

EXPERIMENTAL

500 mg Twice Daily for 7 days

Drug: Nitazoxanide

Interventions

Nitazoxanide DRUG

500 mg Twice Daily for 7 days

Also known as: NTZ

Healthy Control Match (RF ≥ 90 mL/min); Mild Renal Impairment (RF ≥ 60 to < 90 mL/min); Moderate Renal Impairment (RF ≥ 30 to < 60 mL/min); Severe Renal Impairment (RF < 30 mL/min and not on dialysis)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, between 18 and 80 years of age, inclusive
• With a minimum body weight of ≥ 50.0 kg for males and ≥ 45.0 kg for females 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
• Matched to subjects with mild, moderate and/or severe renal impairment in age (± 15 years), BMI (± 20%) and sex
• The diagnosis of renal impairment has been stable, without significant change in overall disease status in the last 3 months prior to screening

You may not qualify if:

• Positive serum pregnancy test at screening or positive urine pregnancy test
• Having taken NTZ at any time prior to the first study drug administration
• History of alcohol abuse within 1 year prior to screening
• History of drug abuse within 1 year prior to screening or recreational use of soft drugs within 1 month or hard drugs within 3 months prior to screening
• Excessive consumption of xanthine-based drinks (\> 4 cups or glasses per day), food or beverages containing xanthine derivatives or xanthine-based compounds, 48 hours prior to the first dosing
• Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to the first dosing
• Strenuous exercise within 72 hours prior to check-in
• History of a major surgical procedure within 30 days prior to screening
• 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
• Subjects who are taking warfarin or other highly plasma protein-bound drugs with narrow therapeutic indices

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

Renal Insufficiency; Kidney Diseases

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital 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: April 12, 2022
• First Posted: May 10, 2022
• Study Start: April 25, 2022
• Primary Completion: September 4, 2022
• Study Completion: September 9, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)