Effect of Omeprazole and Ritonavir on GSK2336805 Pharmacokinetics in Healthy Adults

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01458054
First received: October 6, 2011
Last updated: December 8, 2011
Last verified: December 2011
  Purpose

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


Condition Intervention Phase
Hepatitis C, Chronic
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)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1, Open Label Study to Evaluate the Effect of Omeprazole and Ritonavir on GSK2336805 Pharmacokinetics in Healthy Adults

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • area under the plasma concentration time curve from time zero to the last quantifiable time points [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • under the plasma concentration time curve from time zero to infinity [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • area under the plasma concentration time curve from time zero to 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • maximum observed concentration [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • time to maximum observed concentration [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • concentration at 24 hours post-dose [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • last measureable concentration [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • time of last measurable concentration [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • absorption lag time [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • the elimination half-life [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • apparent oral clearance [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter

  • apparent volume of distribution [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    PK parameter


Secondary Outcome Measures:
  • Number of subjects with Adverse Events [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Safety parameter

  • Number of subjects needing concurrent medications [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Safety parameter

  • Number of subjects with clinical laboratory tests of clinical significance [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Safety parameter

  • Number of subjects with electrocardiograms with clinically significant values [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Safety parameter

  • Number of subjects with vital sign measures of clinical significance [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Safety parameter


Enrollment: 28
Study Start Date: September 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01458054

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01458054     History of Changes
Other Study ID Numbers: 115711
Study First Received: October 6, 2011
Last Updated: December 8, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
pharmacokinetics
omeprazole
ritonavir
healthy subjects
drug interaction

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Flaviviridae Infections
Hepatitis
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Omeprazole
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Anti-Ulcer Agents
Antiviral Agents
Enzyme Inhibitors
Gastrointestinal Agents
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014