Nitazoxanide Pharmacokinetic Parameters in Renal Impaired Subjects

Renal Impairment Clinical Trial

Official title:

An Open-label, Phase 1, Multiple-dose Study to Evaluate the Pharmacokinetics of Nitazoxanide 500 mg Twice Daily for 7 Days in Adult Subjects With Mild, Moderate, and Severe Renal Impairment and Adult Healthy Control Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05368935
• Other study ID #: NTZ-122-1
• Status: Completed
• Phase: Phase 1
• Start date: April 25, 2022
• Est. completion date: September 9, 2022

Study information

• Verified date: October 2022
• Source: Genfit
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This study is being conducted to assess the pharmacokinetics of the major Nitazoxanide active metabolite as well as the safety and tolerability in renal impaired (mild, moderate and severe) and healthy matched control adults following repeated oral dose administration of NTZ 500 mg twice a day for 7 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: September 9, 2022
• Est. primary completion date: September 4, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Males or females, between 18 and 80 years of age, inclusive

2. 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

3. 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

4. Matched to subjects with mild, moderate and/or severe renal impairment in age (± 15 years), BMI (± 20%) and sex

5. The diagnosis of renal impairment has been stable, without significant change in overall disease status in the last 3 months prior to screening

Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

1. Positive serum pregnancy test at screening or positive urine pregnancy test

2. Having taken NTZ at any time prior to the first study drug administration

3. History of alcohol abuse within 1 year prior to screening

4. 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

5. 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

6. 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

7. Strenuous exercise within 72 hours prior to check-in

8. History of a major surgical procedure within 30 days prior to screening

9. Presence or history of malignancy within the prior 3 years, with the exception of treated basal cell or squamous cell carcinoma

10. Poor peripheral venous access

11. Subjects who are taking warfarin or other highly plasma protein-bound drugs with narrow therapeutic indices

Other protocol-defined exclusion criteria may apply

Related Conditions & MeSH terms

• Kidney Disease
• Kidney Diseases
• Renal Disease
• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Nitazoxanide
500 mg Twice Daily for 7 days

Locations

Country	Name	City	State
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genfit

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Time of the maximum observed plasma concentration (Tmax) for NTZ and its major active metabolite	Plasma pharmacokinetics	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
Secondary	Apparent plasma terminal elimination half-life (t1/2) for the NTZ and its major active metabolite	Plasma pharmacokinetics	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
Secondary	Unbound fraction in plasma defined as total concentration/unbound concentration (fu) for the NTZ and its major active metabolite	Plasma pharmacokinetics	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
Secondary	Area under the plasma concentration-time curve from time zero to infinity (extrapolated) (AUC0-8) for the NTZ and its major active metabolite	Plasma pharmacokinetics	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
Secondary	Trough concentration (Ctrough) for the NTZ and its major active metabolite	Plasma pharmacokinetics	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
Secondary	Cmax for the NTZ major active metabolite	Plasma pharmacokinetics	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
Secondary	AUC0-12 for the NTZ major active metabolite	Plasma pharmacokinetics	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
Secondary	AUC0-t for the NTZ major active metabolite	Plasma pharmacokinetics	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
Secondary	Amount of drug excreted in urine over the time interval between t1 and t2 (Aet1-t2) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Cumulative amount of drug excreted in urine from time zero until and up to infinity (Ae0-8) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Cumulative amount of drug excreted in urine from time zero until the last measured concentration at time t (Ae0-t) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Percentage of dose excreted in urine over the time interval between t1 and t2 (Fet1-t2) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Cumulative percent of dose excreted in urine from time zero until the last measured concentration at time t (Fe0-t) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Renal clearance (CLR) for the NTZ major active metabolites	Urine pharmacokinetics	Day (D) 1: pre-dose, 0-4 hours (h); 4-8 h; and 8-12 h post-morning dose; D7: 0-4 h; 4-8 h; 8-12 h; 12- 24 h; 24-48 h; 48-72 h and 72-96 h post-dose
Secondary	Cmax after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	AUC0-12 after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	AUC0-t after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	AUC0-8 after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	Tmax after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	t1/2 after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	Aet1-t2 after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	Amount of drug excreted in urine from time zero to 12h (Ae0-12) after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	Fet1-t2 after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	Cumulative percent of dose excreted in urine from time zero to 12h (Fe0-12) after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose
Secondary	CLR after the single oral administration of NTZ 500 mg for the NTZ major active metabolites	Plasma and urine pharmacokinetics	D1:predose;1;2;3;4;5;6;7;8;10;12h post dose; D2-6:predose; D7:predose;1;2;3;4;5;6;7;8;10;12;14;16;18; 24(D8);48(D9);72(D10) and 96(11)h post-dose.Urine:D1 predose; 0-4; 4-8; 8-12 h post morning dose; D7 0-4;4-8;8-12;12- 24;24-48;48-72;72-96h post-dose