A Study to Evaluate the Bioequivalence of Over-encapsulated Oseltamivir Capsules to Marketed Oseltamivir Capsules in Healthy Volunteers

A Randomized, Open-label, Single-Dose, Two-Period, Crossover Study to Evaluate the Bioequivalence of Over-encapsulated Oseltamivir Capsules to Marketed Oseltamivir Capsules in Healthy Volunteers

This is a study in healthy adult volunteers to assess the bioequivalence of over-encapsulated oseltamivir capsules to commercially available oseltamivir capsules. Both formulations will be administered in the fasting state.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Drug: over-encapsulated oseltamivir; Drug: oseltamivir

• 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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin greater than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• 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: Child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit.
• Body weight greater than or equal to 50 kg and BMI within the range 18.5 - 31.0 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• 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 mL within a 56 day period.
• Pregnant females as determined by positive serum or urine hCG 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.
• Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.
• The subject's systolic blood pressure is outside the range of 90-140 mmHg, or diastolic blood pressure is outside the range of 45-90 mmHg or heart rate is outside the range of 50-100 bpm for female subjects or 45-100 bpm for male subjects.
• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate Males <45 and >100 bpm Females <50 and >100 bpm; PR Interval <120 and >220 msec; QRS duration <70 and >120 msec; QTc interval (Bazett) >450 msec.

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, non-sustained or sustained ventricular tachycardia (greater than or equal to 3 consecutive ventricular ectopic beats).sinus pauses > 3 seconds, or other significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; Over-encapsulated oseltamivir 75 mg (1 capsule)	Drug: over-encapsulated oseltamivir; 75 mg once
EXPERIMENTAL: Treatment B; oseltamivir 75 mg (1 capsule)	Drug: oseltamivir; 75 mg once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma oseltamivir carboxylate area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity))	9 days
Plasma oseltamivir carboxylate maximum observed concentration (Cmax)	9 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma oseltamivir carboxylate area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration (AUC(0-t))	9 days
Plasma oseltamivir carboxylate terminal phase half-life (t1/2)	9 days
Plasma oseltamivir carboxylate time of occurrence of Cmax (tmax)	9 days
Plasma oseltamivir AUC (0-infinity)	9 days
Plasma oseltamivir AUC(0-t)	9 days
Plasma oseltamivir Cmax	9 days
Plasma oseltamivir t1/2	9 days
Plasma oseltamivir lag time before observation of drug concentrations in sampled matrix (tlag)	9 days
Plasma oseltamivir tmax	9 days
Safety and tolerability of all treatments, including number of subjects with adverse events assessment	4 weeks
Safety and tolerability of all treatments, including number of subjects with concurrent medications	4 weeks
Safety and tolerability of all treatments, change from baseline and number subjects with abnormal clinical safety laboratory data	4 weeks
Safety and tolerability of all treatments, including change from baseline and number of subjects with abnormal ECG assessments	4 weeks
Safety and tolerability of all treatments, including change from baseline and number of subjects with abnormal vital signs (blood pressure and heart rate) assessments	4 weeks
Plasma oseltamivir carboxylate lag time before observation of drug concentrations in sampled matrix(tlag)	9 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2010
• Primary Completion (ACTUAL): February 3, 2011
• Study Completion (ACTUAL): February 3, 2011

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: December 9, 2010
• First Posted (ESTIMATE): December 13, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: influenza, bioequivalence, oseltamivir, Tamiflu, over-encapsulation
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: 115096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 115096
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register