IVIVR Assessing PK Parameters Used to Establish Bioequivalence

NCT02398448 | Completed Phase 1

• 1 other identifier: ALLO-101(QCL116986)
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• PK profile of Zyloprim® and three dissolution test formulations of allopurinol from plasma

  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)

  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.

Secondary Outcomes (1)

• Incidence of Adverse Events

  11 weeks

Study Arms (1)

Zyloprim® 300 mg and three dissolution test formulations

EXPERIMENTAL

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

Drug: Zyloprim® 300 mg; Drug: Allopurinol 300 mg; undergranulated, high hardness condition; Drug: Allopurinol 300 mg; alternative condition 2; Drug: Allopurinol 300 mg; alternative condition 3

Interventions

Zyloprim® 300 mg DRUG

Zyloprim® 300 mg and three dissolution test formulations

Allopurinol 300 mg; undergranulated, high hardness condition DRUG

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

Zyloprim® 300 mg and three dissolution test formulations

Allopurinol 300 mg; alternative condition 2 DRUG

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

Zyloprim® 300 mg and three dissolution test formulations

Allopurinol 300 mg; alternative condition 3 DRUG

Zyloprim® 300 mg and three dissolution test formulations

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead
• Quotient Clinical: collaborator

Study Sites (1)

Unknown Facility

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Allopurinol

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Chris Storgard

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2015
• First Posted: March 25, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 1, 2016

Record last verified: 2015-12

Locations

GB (1)