HealthyPhase 1NCT02398448
IVIVR Assessing PK Parameters Used to Establish Bioequivalence
A Phase 1 study testing Zyloprim® 300 mg, Allopurinol 300 mg; undergranulated, high hardness condition and Allopurinol 300 mg; alternative condition 2 in people with Healthy, run by Ardea Biosciences, Inc. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Zyloprim® 300 mg, Allopurinol 300 mg; undergranulated, high hardness condition and Allopurinol 300 mg; alternative condition 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2015to Sep 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 16Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Zyloprim® 300 mg, Allopurinol 300 mg; undergranulated, high hardness condition, Allopurinol 300 mg; alternative condition 2, Allopurinol 300 mg; alternative condition 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zyloprim® 300 mgDrug
Allopurinol 300 mg; undergranulated, high hardness conditionDrug
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
Allopurinol 300 mg; alternative condition 2Drug
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
Allopurinol 300 mg; alternative condition 3Drug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Changes in Laboratory, Electrocardiogram and Vital Signs Parameters
Measured: 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startApr 2015
- Primary completionJul 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ardea Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quotient Clinical
- Responsible party
- Sponsor
- Investigators
- Chris Storgard, Study director, Ardea Biosciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398448
- Sponsor's protocol ID
- ALLO-101(QCL116986)
- Status last verified
- Dec 2015
- First submitted
- 20 Mar 2015
- Last updated
- 1 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vitro-In Vivo Relationship Study to Assess the Impact of the In Vitro Dissolution Profile on the Pharmacokinetic Parameters Used to Establish Bioequivalence
- ClinicalTrials.gov ID
- NCT02398448
- Acronym / sponsor ID
- ALLO-101(QCL116986)
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Ardea Biosciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Quotient Clinical
- Study start
- Apr 2015
- Primary completion
- Jul 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zyloprim® 300 mg and three dissolution test formulations | Experimental | 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 3Regimen 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zyloprim® 300 mg | Drug | Zyloprim® 300 mg and three dissolution test formulations |
| Allopurinol 300 mg; undergranulated, high hardness conditionThere 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 | Drug | Zyloprim® 300 mg and three dissolution test formulations |
| Allopurinol 300 mg; alternative condition 2There 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 | Drug | Zyloprim® 300 mg and three dissolution test formulations |
| Allopurinol 300 mg; alternative condition 3 | Drug | Zyloprim® 300 mg and three dissolution test formulations |
Primary outcome
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.
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)
1 secondary outcome
Incidence of Adverse Events
Time frame: 11 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2016.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Storgard study director
Ardea Biosciences, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zyloprim® 300 mg, Allopurinol 300 mg; undergranulated, high hardness condition and Allopurinol 300 mg; alternative condition 2 in people with Healthy, run by Ardea Biosciences, Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2016.