Pharmacokinetic (PK) Profiles of Tenofovir Disoproxil Fumarate (TDF) 300 mg in Healthy Chinese Subjects (PK of TDF)

An Open-label Single and Repeat Dose Study to Investigate the Pharmacokinetic Profiles of Tenofovir Disoproxil Fumarate 300 mg in Healthy Chinese Subjects

This study will evaluate the pharmacokinetic profile of tenofovir disoproxil fumarate (TDF) 300 mg in Chinese subjects to support the registration of this compound in the People's Republic of China. This will be an open-label, single group, single and repeat dose study without placebo in healthy male and female subjects. Pharmacokinetic sampling to enable measurement of plasma concentrations of tenofovir will be conducted over a 60-h period after the single dose and at steady state. The duration of the study will be approximately 7 weeks from screening to follow-up.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: TDF tablets

Detailed Description

This will be an open-label, single group, single and repeat dose study with no placebo control in healthy Chinese subjects conducted at a single centre. The study will include a screening visit, single and repeat dose sessions and a follow-up contact.

The screening visit will be conducted up to 28 days prior to the first dose of treatment period 1. Screening assessments will occur as indicated in the Time and Events Table.

Subjects who meet the inclusion/exclusion criteria will be admitted to the study centre on Day -1 to undergo baseline procedures before the single dose session. Study medication will be administered the following morning (Day 1) for the single dose phase. Subjects will be required to fast for at least 8 h (overnight) prior to dosing until 4 h after dosing. Pharmacokinetic samples will be taken until Day 3.

The repeat dose session will begin on Day 4. Subjects will receive a once daily dose of TDF 300 mg in a fasted state each morning for 7 days. Subjects will be required to fast for at least 8 h (overnight) prior to dosing on Day 8 and Day 9, and for at least 8 h (overnight) prior to dosing until 4 h after dosing on Day 10. A trough pharmacokinetic sample will be collected before dosing on Day 8, Day 9 and a series of samples will be taken from Day 10 to Day 12.

Subjects will remain in-house from the evening before dosing (Day -1) until after the final pharmacokinetic sample has been collected on Day 12 and the final safety assessment completed on Day 13. Then subjects will be discharged from the study centre at the Investigator's discretion.

Subjects completing the dosing sessions will not be required to visit the study centre for a follow-up visit, unless the Investigator determines that it is necessary for safety or other reasons. All subjects will receive a follow-up contact by telephone or visit 7 days after the last dosing to collect any information on concomitant medication taken and AEs experienced since the last visit.

The total duration of each subject's participation, from screening to follow-up contact, will be approximately 7 weeks.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200030
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, as determined by a responsible and experienced physician
• Male or female between 18 and 45 years of age
• Body weight >50 kg (110 lbs) for males or >45 kg (100 lbs) for females, and body mass index (BMI) between 19.0 and 24.0 kg/m2

Exclusion Criteria:

• Positive result for hepatitis B, hepatitis C or HIV at screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities
• Positive urine drug screen and breath alcohol test at screening or prior to dosing
• Lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDF tablets; Tenofovir disoproxil fumarate tablets	Drug: TDF tablets; White, almond-shaped, film-coated tablets, one side with the markings "GILEAD" and "4331"

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t))	AUC(0-t) of single dose	up to 60 hours after single dose
area under the concentration-time curve during steady state (AUC(0-τ))	AUC(0-τ) during steady state	up to 60 hours after repeat dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events (AEs)	AEs accur during the study	up to 20 days, from the first dose until the follow-up contact
vital signs	blood pressure, pulse rate, respiratory rate and temperature	day 1 pre-dose, day 2, day 3, day 10 pre-dose, day 11, day 12 and day 13 prior to discharge from hospital
lab assessment	Haematology, Clinical Chemistry and Routine Urinalysis	day 13, prior to discharge from hospital
12-lead electrocardiogram (ECG) parameters	the heart rate and measures PR, QRS, QT and QTc intervals. All ECGs must be evaluated for safety by a qualified physician.	day 13, prior to discharge from hospital

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Hu CY, Liu YM, Liu Y, Chen Q, Wang W, Wu K, Dong J, Li J, Jia JY, Lu C, Sun SX, Yu C, Li X. Pharmacokinetics and tolerability of Tenofovir disoproxil fumarate 300 mg once daily: an open-label, single- and multiple-dose study in healthy Chinese subjects. Clin Ther. 2013 Dec;35(12):1884-9. doi: 10.1016/j.clinthera.2013.09.020. Epub 2013 Oct 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2011
• Primary Completion (Actual): December 30, 2011
• Study Completion (Actual): December 30, 2011

Study Registration Dates

• First Submitted: November 17, 2011
• First Submitted That Met QC Criteria: November 23, 2011
• First Posted (Estimate): November 29, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy subjects; Tenofovir disoproxil fumarate; hepatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic
• Other Study ID Numbers: 115515