Effect of Omeprazole and Ritonavir on GSK2336805 Pharmacokinetics in Healthy Adults

Phase 1, Open Label Study to Evaluate the Effect of Omeprazole and Ritonavir on GSK2336805 Pharmacokinetics in Healthy Adults

This study is a Phase I open label drug interaction study to evaluate the effect of omeprazole and ritonavir on GSK2336805.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Cohort 1 (GSK2336805 60mg x 1 dose, Omeprazole 40 mg q24h x 4 days, GSK2336805 60 mg x 1 dose and Omeprazole 40 mg x 1 dose); Drug: Cohort 2 (GSK2336805 30mg x 1 dose, Ritonavir 100mg q12h x 4 days, and Ritonavir 100mg q12h x 1 dose)

Detailed Description

This study is a Phase I open label drug interaction study with two objectives. The first objective of this study (Cohort 1) is to determine if the pharmacokinetics of a single dose of GSK2336805 are affected by co-administration with repeat doses of omeprazole, a proton-pump inhibitor that is commonly used by chronic hepatitis C patients .

The second objective of this study (Cohort 2) is to determine if the pharmacokinetics of a single dose of GSK2336805 are affected by co-administration with repeat doses of ritonavir, a HIV protease inhibitor drug that is a potent inhibitor of CYP 3A4.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14202
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin greater than or equal to 1.5x Upper Limit of Normal (ULN) (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with values outside the normal range should always be excluded from enrollment.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:

Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, oophorectomy, or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea

• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit.
• Body weight greater than or equal to 50 kilograms for men and greater than or equal to 45 kilograms for women. Body mass index (BMI) between 18.5-32 inclusive will be allowed (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• QTcB less than 450; or QTc less than 480 in subjects with Bundle Branch Block

Exclusion Criteria:

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters within a 56 day period.
• Pregnant females as determined by positive serum or urine human chorionic gonadotropin test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• The subject's systolic blood pressure is outside the range of 90-140, or diastolic blood pressure is outside the range of 45-90 or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 beats per minute for male subjects.
• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):Heart rate less than 45 and greater than 100 bpm for men and less than 50 and greater than 100 bpm for women. PR interval less than 120 and greater than 220. QRS duration less than 70 and greater than 120. QTc interval greater than 450. Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome). Sinus Pauses greater than 3 seconds. Any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety for the individual subject. Non-sustained or sustained ventricular tachycardia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; GSK2336805 60mg x 1 dose (fasted) [Reference Treatment]	Drug: Cohort 1 (GSK2336805 60mg x 1 dose, Omeprazole 40 mg q24h x 4 days, GSK2336805 60 mg x 1 dose and Omeprazole 40 mg x 1 dose); GSK2336805 and Omeprazole
Experimental: Treatment B; Omeprazole 40 mg q24h x 4 days (fed)	Drug: Cohort 1 (GSK2336805 60mg x 1 dose, Omeprazole 40 mg q24h x 4 days, GSK2336805 60 mg x 1 dose and Omeprazole 40 mg x 1 dose); GSK2336805 and Omeprazole
Experimental: Treatment C; GSK2336805 60 mg x 1 dose and Omeprazole 40 mg on Day 1 (fasted) [Test Treatment]	Drug: Cohort 1 (GSK2336805 60mg x 1 dose, Omeprazole 40 mg q24h x 4 days, GSK2336805 60 mg x 1 dose and Omeprazole 40 mg x 1 dose); GSK2336805 and Omeprazole
Experimental: Treatment D; GSK2336805 30mg x 1 dose (fasted) [Reference Treatment]	Drug: Cohort 2 (GSK2336805 30mg x 1 dose, Ritonavir 100mg q12h x 4 days, and Ritonavir 100mg q12h x 1 dose); GSK2336805 and Ritonavir
Experimental: Treatment E; Ritonavir 100mg q12h x 4 days (fed)	Drug: Cohort 2 (GSK2336805 30mg x 1 dose, Ritonavir 100mg q12h x 4 days, and Ritonavir 100mg q12h x 1 dose); GSK2336805 and Ritonavir
Experimental: Treatment F; GSK2336805 30 mg x 1 dose (fasted) and ritonavir 100mg q12h on Day 1 (fasted) [Test Treatment]	Drug: Cohort 2 (GSK2336805 30mg x 1 dose, Ritonavir 100mg q12h x 4 days, and Ritonavir 100mg q12h x 1 dose); GSK2336805 and Ritonavir
Experimental: Treatment G; Ritonavir 100mg q12h x 1 day	Drug: Cohort 2 (GSK2336805 30mg x 1 dose, Ritonavir 100mg q12h x 4 days, and Ritonavir 100mg q12h x 1 dose); GSK2336805 and Ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the plasma concentration time curve from time zero to the last quantifiable time points	PK parameter	48 hours
under the plasma concentration time curve from time zero to infinity	PK parameter	48 hours
area under the plasma concentration time curve from time zero to 24 hours	PK parameter	24 hours
maximum observed concentration	PK parameter	48 hours
time to maximum observed concentration	PK parameter	48 hours
concentration at 24 hours post-dose	PK parameter	24 hours
last measureable concentration	PK parameter	48 hours
time of last measurable concentration	PK parameter	48 hours
absorption lag time	PK parameter	48 hours
the elimination half-life	PK parameter	48 hours
apparent oral clearance	PK parameter	48 hours
apparent volume of distribution	PK parameter	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with Adverse Events	Safety parameter	24 hours
Number of subjects needing concurrent medications	Safety parameter	24 hours
Number of subjects with clinical laboratory tests of clinical significance	Safety parameter	24 hours
Number of subjects with electrocardiograms with clinically significant values	Safety parameter	24 hours
Number of subjects with vital sign measures of clinical significance	Safety parameter	24 hours

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2011
• Primary Completion (Actual): November 28, 2011
• Study Completion (Actual): November 28, 2011

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 20, 2011
• First Posted (Estimate): October 24, 2011

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy subjects; drug interaction; ritonavir; omeprazole
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Gastrointestinal Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Omeprazole
• Other Study ID Numbers: 115711