Pharmacokinetics and Safety of the Co-administration of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Healthy Chinese Subjects

Multiple-Dose Pharmacokinetics, Safety and Tolerability of the Co-administration of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Healthy Chinese Subjects

The purpose of this study is to assess the pharmacokinetics and safety of multiple oral doses of ABT-450/ritonavir/ABT-267 and ABT-333 when co-administered under non-fasting conditions in healthy Chinese adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: ABT-333; Drug: ABT-450/r/ABT-267

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200031
    • Site Reference ID/Investigator# 137655

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: Participant must be Chinese (i.e., of Chinese ancestry).

If female, participant must be either postmenopausal for at least 2 years, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control with male partner(s): total abstinence from sexual intercourse as the preferred life style of the subject, periodic abstinence is not acceptable; vasectomized partner(s); hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration; intrauterine device (IUD); or double-barrier method (condoms, contraceptive sponge, or diaphragm with spermicidal jellies or creams)

Hormonal contraceptives, including but not limited to oral, topical, injectable or implantable varieties, may not be used during the study.

If male, the participant must be surgically sterile or practicing at least 1 of the following methods of contraception, and refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug: partner(s) using an IUD; partner(s) using oral, injected, intravaginal, or implanted methods of hormonal contraceptives; participant and/or partner(s) using double-barrier method (condoms, contraceptive sponge, diaphragm with spermicidal jellies or creams, or vaginal ring); or total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable

Body Mass Index (BMI) is ≥ 18 to < 30 kg/m^2.

A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile, a 12-lead electrocardiogram (ECG) and chest x-ray (CXR).

Exclusion Criteria: Use of any medications (prescription and over-the-counter), vitamins and/or herbal supplements within the 2-week period prior to the first dose of study drug administration or within 10 half-lives of the respective medication, whichever is longer.

History of epilepsy, any clinically significant cardiovascular, respiratory (except mild asthma), renal, hepatic, gastrointestinal, hematologic, neurologic, thyroid, or any uncontrolled medical illness or psychiatric disease or disorder.

Clinically significant abnormal ECG: ECG with QT interval corrected for heart rate using Fridericia's correction formula (QTcF) > 450 msec in females and > 430 msec in males, or ECG with second or third degree atrioventricular block.

Previous exposure to more than a single dose of ABT-450/r/ABT-267, or ABT-333 within the past 12 weeks, or previous participation in this study.

Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-450, ritonavir, ABT-267, or ABT-333.

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: ABT-450/r/ABT-267 + ABT-333; ABT-450/r/ABT-267 will be administered once daily in the morning and ABT-333 will be administered in the morning and evening for 14 days.	Drug: ABT-333; Tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; Tablet; Other Names: Paritaprevir/Ritonavir/Ombitasvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of ABT-450	Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Maximum Plasma Concentration (Cmax) of ABT-267	Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Maximum Plasma Concentration (Cmax) of ABT-333	Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Maximum Plasma Concentration (Cmax) of Ritonavir	Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Time to Maximum Plasma Concentration (Tmax) of ABT-450	Tmax is the time it takes for a drug to achieve Cmax.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Time to Maximum Plasma Concentration (Tmax) of ABT-267	Tmax is the time it takes for a drug to achieve Cmax.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Time to Maximum Plasma Concentration (Tmax) of ABT-333	Tmax is the time it takes for a drug to achieve Cmax.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Time to Maximum Plasma Concentration (Tmax) of Ritonavir	Tmax is the time it takes for a drug to achieve Cmax.	Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14; and 36, 48, and 72 hours after the morning dose on Study Day 14
Trough Concentration (Ctrough) of ABT-450	Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.	Prior to the morning dose on Study Days 7, 9, 11, 13 and 14; 24 hours after Day 14 dose
Trough Concentration (Ctrough) of ABT-267	Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.	Prior to the morning dose on Study Days 7, 9, 11, 13 and 14; 24 hours after Day 14 dose
Trough Concentration (Ctrough) of ABT-333	Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.	Prior to the morning dose on Study Days 7, 9, 11, 13 and 14; 24 hours after Day 14 dose
Trough Concentration (Ctrough) of Ritonavir	Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.	Prior to the morning dose on Study Days 7, 9, 11, 13 and 14; 24 hours after Day 14 dose
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450		Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir		Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267		Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, 12, 15, 18, and 24 hours after the morning dose on Study Days 1 and 14
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333		Prior to the morning dose (0 hour) and 1, 2, 3, 4, 6, 9, and 12 hours after the morning dose on Study Days 1 and 14
Number of participants with adverse events		Daily for approximately 20 days

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Zha J, Ding B, Wang H, Zhao W, Yu C, Alves K, Mobashery N, Luo Y, Menon RM. Pharmacokinetics of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir in Healthy Chinese Subjects and HCV GT1b-Infected Chinese, South Korean and Taiwanese Patients. Eur J Drug Metab Pharmacokinet. 2019 Feb;44(1):43-52. doi: 10.1007/s13318-018-0492-8.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 26, 2015
• First Submitted That Met QC Criteria: August 26, 2015
• First Posted (Estimate): August 28, 2015

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Volunteer
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: M13-769