- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02398448
IVIVR Assessing PK Parameters Used to Establish Bioequivalence
December 31, 2015 updated by: Ardea Biosciences, Inc.
In Vitro-In Vivo Relationship Study to Assess the Impact of the In Vitro Dissolution Profile on the Pharmacokinetic Parameters Used to Establish Bioequivalence
The purpose of this study is to determine whether defined and limited changes in in vitro dissolution impact the in vivo pharmacokinetics (PK) and relative bioavailability of allopurinol and the active metabolite oxypurinol.
Study Overview
Status
Completed
Conditions
Detailed Description
In this study, a single oral dose of Zyloprim® (300 mg tablet) and 3 separate single oral doses of 300 mg allopurinol test formulations (Regimens B, C and D) will be administered sequentially to each subject on separate occasions.
Following the administration of Regimens B and C, there will be a period of interim analysis during which the PK data will be reviewed to determine the formulation within the process design space that provides the desired in vitro dissolution variant for dosing in the subsequent study period.
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ruddington, United Kingdom, NG11 6JS
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Body mass index of 18.0 to 35.0 kg/m2 inclusive, or if outside the range, considered not clinically significant by the Investigator. Must not exceed 40.0 kg/m2.
- Must agree to use an adequate method of contraception
Exclusion Criteria:
- Subjects who test positive for the HLA-B*5801 allele.
- Subjects who have received the last dose of an IMP (or treatment with a medical device) within the previous 3 months prior to Day 1 or is currently participating in another study of an IMP (or medical device).
- History of any drug or alcohol abuse in the past 2 years.
- Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
- Current smokers and those who have smoked within the last 12 months prior to Screening. A breath carbon monoxide reading of greater than 10 ppm at Screening.
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at Screening.
- Clinically significant screening laboratory parameters (biochemistry [AST or ALT > 1.5 × ULN], hematology or urinalysis) as judged by the Investigator (laboratory parameters are listed in Appendix 1).
- Positive drugs of abuse test result during Screening or at Admission (drugs of abuse tests are listed in Appendix 1).
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
- Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
- History of cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease as judged by the Investigator.
- Evidence of renal impairment at Screening, as indicated by an estimated creatinine clearance of <90 mL/min using the Cockcroft-Gault equation.
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
- Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hayfever is allowed unless it is active.
- Donation or loss of greater than 400 mL of blood within the previous 3 months prior to Screening.
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than up to 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration (See Section 11.4).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Zyloprim® 300 mg and three dissolution test formulations
Regimen A: Zyloprim® 300 mg; Regimen B: Allopurinol 300 mg; undergranulated, high hardness condition; Regimen C: Allopurinol 300 mg; alternative condition 2; Regimen D: Allopurinol 300 mg; alternative condition 3
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There will be a period for interim analysis after administration of Regimen B to determine the formulation within the process design space that provides the desired in vitro dissolution variant for dosing in the subsequent study period
There will be a period for interim analysis after administration of Regimen C to determine the formulation within the process design space that provides the desired in vitro dissolution variant for dosing in the subsequent study period
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PK profile of Zyloprim® and three dissolution test formulations of allopurinol from plasma
Time Frame: Predose (within 30 minutes before dosing), 15, 30, and 45 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours postdose.
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PK endpoints in terms of maximum observed concentration (Cmax), time of occurrence of maximum observed concentration (Tmax), area under the concentration-time curve (AUClast), area under the concentration-time curve (AUC∞) and apparent terminal half-life (t1/2)
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Predose (within 30 minutes before dosing), 15, 30, and 45 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours postdose.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events
Time Frame: 11 weeks
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Changes in Laboratory, Electrocardiogram and Vital Signs Parameters
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11 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Chris Storgard, Ardea Biosciences, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2015
Primary Completion (Actual)
July 1, 2015
Study Completion (Actual)
September 1, 2015
Study Registration Dates
First Submitted
March 20, 2015
First Submitted That Met QC Criteria
March 20, 2015
First Posted (Estimate)
March 25, 2015
Study Record Updates
Last Update Posted (Estimate)
January 1, 2016
Last Update Submitted That Met QC Criteria
December 31, 2015
Last Verified
December 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALLO-101(QCL116986)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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