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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This study will be conducted to investigate the safety of verinurad in healthy volunteers in combination with allopurinol 300 mg, compared with placebo in particular its effect on electrocardiogram (ECG), with focus on the QT/QTc interval
This study will be conducted as a single-centre, randomised, placebo-controlled, double-blind, 3-period, crossover study to assess the effect on the QTcF interval of a single oral dose of verinurad 24 mg extended release (ER8) formulation (therapeutic exposure) or verinurad 40 mg immediate release (IR) formulation (supra-therapeutic exposure), each in combination with allopurinol 300 mg, compared to placebo in healthy subjects.
There are 3 study treatments:
All subjects will receive a single dose of all 3 treatments (A, B, and C) in a cross-over design with wash-out periods of at least 7 days between each study dose administration.
Subjects will be randomised to the treatment sequence (ABC, BCA, CAB, etc.) using William's Latin square. The treatments will be administered in a double-blind manner after an overnight fast of at least 10 hours.
The study will comprise the following periods (visits):
Each subject will be involved in the study for approximately 53 days and have 5 study visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment ABC | Experimental | Subjects will receive a single dose of all 3 treatments (A, B, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
|
| Treatment BCA | Experimental | Subjects will receive a single dose of all 3 treatments (B, C, and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
|
| Treatment CAB | Experimental | Subjects will receive a single dose of all 3 treatments (C, A, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
|
| Treatment ACB | Experimental | Subjects will receive a single dose of all 3 treatments (A, C, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
|
| Treatment BAC | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Verinurad | Drug | Randomized subjects will receive oral dose of verinurad |
|
| Measure | Description | Time Frame |
|---|---|---|
| Model Predicted Baseline-corrected and Placebo-corrected QT Interval Corrected for Heart Rate (HR) Using Fridericia's Formula (QTcF)(ΔΔQTcF) (Derived From Concentration-QTcF Analysis) at Geometric Mean of Cmax of Verinurad | Assessment of the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of International Council for Harmonisation Guideline E14 and associated Questions and Answers [ICH E14 Q&A]), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF analysis. A linear mixed-effect concentration-QTcF model was used as the primary analysis. This is a result of the statistical model so it does not have values for every timepoint, it is just one set of numbers - summarizes data across all timepoints. No non-placebo-corrected QTcF data values were collected or could be obtained for each Arm/Group at Cmax of Verinurad. | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline-corrected Heart Rate (ΔHR) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on heart rate (HR). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hour (h) post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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Inclusion Criteria:
(1) Not pregnant or currently lactating or breast-feeding. (2) Of non-childbearing potential confirmed at the Screening Visit by fulfilling one of the following criteria: (i) Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range (FSH >40 IU/mL).
(ii) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
(3) OR, if of childbearing potential, must be willing to use an acceptable method of contraception to avoid pregnancy for the entire study period and 3 months after the Follow-up Visit.
4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
5. Serum uric acid (sUA) <300 μmol/L at Screening (Visit 1) and sUA <330 μmol/L on Day -1 in every treatment period (Visit 2 to 4). Note: Since sUA levels might vary on a daily basis, subjects with sUA ≥330 μmol/L on Day -1 will be retested. Treatment on Day 1 will only be administered when the sUA level on Day -1 is <330 μmol/L upon retesting. Subjects with sUA ≥330 μmol/L despite retesting, may conduct the treatment period at a later date when they have sUA <330 μmol/L.
6. Must be able to swallow multiple capsules/tablets.
Exclusion criteria:
(1) Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) (2) Aspartate aminotransferase (AST) >1.5 × ULN (3) Bilirubin (total) >1.5 × ULN (4) Gamma glutamyl transpeptidase (GGT) >1.5 × ULN 8. Any clinically significant abnormal findings in vital signs at Screening as judged by the Investigator, including:
(1) Systolic blood pressure <90 mmHg or >140 mmHg (2) Diastolic blood pressure <50 mmHg or >90 mmHg (3) Heart rate <50 or >90 bpm 9. Carrier of the HLA-B*58:01 allele. 10. Any clinically important abnormalities in rhythm, conduction or morphology of the 12 lead safety ECG and any clinically important abnormalities in the 12-lead safety ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF), including abnormal ST T wave morphology, particularly in the Clinical Study Protocol (CSP)-defined primary lead for dECG analysis or left ventricular hypertrophy:
11. Any positive result on Screening for serum hepatitis B surface antigen OR anti-HBc antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
12. Suspected or known Gilbert's syndrome. 13. Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to Screening.
14. Known or suspected history of alcohol abuse or excessive intake of alcohol as judged by the Investigator. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g per day for women.
15. Positive screen for drugs of abuse, cotinine (nicotine) or alcohol at the Screening Visit or on each admission to the study centre.
16. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator. Excessive intake of caffeine defined as the regular consumption of more than 600 mg of caffeine per day (eg, >5 cups of coffee) or would likely be unable to refrain from the use of caffeine-containing beverages during confinement at the study site.
17. Previous hypersensitivity reaction to allopurinol or any URAT1 inhibitor. 18. Subjects who are pregnant, breast-feeding or planning to become pregnant (pregnancy is to be avoided for the entire study period and 3 months after the Follow up Visit).
19. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
20. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 × the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or within 5 half-lives (whichever is longer). Hormone replacement therapy is allowed for females.
21. Plasma donation within 1 month of Screening or any blood donation/blood loss >500 mL during the 3 months prior to Screening.
22. Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing in the US) within 30 days or within 5 half lives (whichever is longer) of the first administration of IMP in this study.
Note: Subjects consented and screened, but not randomised in this study or a previous Phase I study, are not excluded.
23. Involvement of any AstraZeneca, Parexel or study site employee or their close relatives.
24. Subjects who have previously received verinurad. 25. Subjects who cannot communicate reliably with the Investigator and/or are not able to read, speak and understand the German language.
26. Judgment by the Investigator that the subject should not participate in the study if there are any ongoing or recent (ie, during the Screening Period) minor medical complaints that may interfere with the interpretation of the study data or are considered unlikely to comply with study procedures, restrictions and requirements.
27. Subjects who are vegans or have medical dietary restrictions. 28. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
29. Subjects who are regularly exposed to COVID-19 (eg, health care professionals working in COVID-19 wards or at emergency departments) as part of their daily life.
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Kӧrnicke, MD | PAREXEL Early Phase Clinical Unit Berlin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Berlin | 14050 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36504291 | Derived | Parkinson J, Dota C, Kallgren C, Gottfridsson C, Bjursell M, Perl S, Kӧrnicke T, Rekic D, Johansson S. Verinurad does not prolong QTc interval: a thorough QT study using concentration-QTc modelling. Br J Clin Pharmacol. 2023 Jun;89(6):1747-1755. doi: 10.1111/bcp.15637. Epub 2023 Jan 2. |
| Label | URL |
|---|---|
| Protocol and Statistical Analysis Plan (SAP) | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
The study consisted of a Screening Period of maximum 28 days. There were wash-out periods of at least 7 days between each study dose administration. The assessments were done as per the schedule of assessment.
This study was conducted in 24 healthy male and female participants at a single study center - Parexel Early Phase Clinical Unit (Berlin).
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence ABC | Randomised participants received single doses of all 3 study treatments (Treatment A: Verinurad 24 mg extended release [ER8] formulation co-administered with 300 mg allopurinol, Treatment B: Verinurad 40 mg immediate release [IR] formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| FG001 | Treatment Sequence BCA | Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| FG002 | Treatment Sequence CAB | Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| FG003 | Treatment Sequence ACB | Randomised participants received single doses of all 3 study treatments ( Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| FG004 | Treatment Sequence BAC | Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| FG005 | Treatment Sequence CBA | Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Sequence ABC | Randomised participants received single doses of all 3 study treatments (Treatment A: Verinurad 24 mg extended release [ER8] formulation co-administered with 300 mg allopurinol, Treatment B: Verinurad 40 mg immediate release [IR] formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Model Predicted Baseline-corrected and Placebo-corrected QT Interval Corrected for Heart Rate (HR) Using Fridericia's Formula (QTcF)(ΔΔQTcF) (Derived From Concentration-QTcF Analysis) at Geometric Mean of Cmax of Verinurad | Assessment of the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of International Council for Harmonisation Guideline E14 and associated Questions and Answers [ICH E14 Q&A]), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF analysis. A linear mixed-effect concentration-QTcF model was used as the primary analysis. This is a result of the statistical model so it does not have values for every timepoint, it is just one set of numbers - summarizes data across all timepoints. No non-placebo-corrected QTcF data values were collected or could be obtained for each Arm/Group at Cmax of Verinurad. | In the Primary Outcome we present the predicted value of ΔΔQTcF based on a statistical model created for the study. The results may be presented for the active arms only, since the placebo arm did not receive Verinurad and thus have no Cmax. Placebo-corrected and baseline adjusted QTcF, ∆∆QTcF with 90% confidence interval at the verinurad maximum concentration of interest is presented as the primary result from the analysis. | Posted | Geometric Mean | 90% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 11, 2020 | Jun 16, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C000628929 | verinurad |
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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This study is double-blind with regards to treatment (verinurad and allopurinol or the matching placebos) at each dose level. Placebo will be matched with verinurad and allopurinol for appearance and amount. Subjects randomized to placebo will receive the same volume of oral suspension as subjects on active drug.
Subjects will receive a single dose of all 3 treatments (B, A, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
|
| Treatment CBA | Experimental | Subjects will receive a single dose of all 3 treatments (C, B and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration. |
|
|
| Placebo | Drug | Randomized subjects will receive oral dose of placebo |
|
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| Allopurinol | Drug | Randomized subjects will receive oral dose of allpurinol (Treatment A and B) |
|
|
| Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on HR. | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected RR Interval (ΔRR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected PR Interval (ΔPR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected QRS Interval (ΔQRS Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected QT Interval (ΔQT Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected QTcF Interval (ΔQTcF Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF). | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
| Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the pharmacokinetic (PK) of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (Parent Drug Only) (CL/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Parent Drug Only) (Vz/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Apparent Volume of Distribution at Steady State Following Extravascular Administration (Parent Drug Only) (Vss/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for Verinurad and Oxypurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
| Number of Participants With Adverse Events (AEs) | Examination of the safety and tolerability of verinurad and allopurinol. | From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose) |
| CSR Synopsis | View source |
| Protocol Violation |
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| BG001 | Treatment Sequence BCA | Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| BG002 | Treatment Sequence CAB | Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| BG003 | Treatment Sequence ACB | Randomised participants received single doses of all 3 study treatments ( Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| BG004 | Treatment Sequence BAC | Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| BG005 | Treatment Sequence CBA | Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions. |
| BG006 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Secondary | Baseline-corrected Heart Rate (ΔHR) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on heart rate (HR). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | Beats per minute (bpm) | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hour (h) post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on HR. | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | bpm | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected RR Interval (ΔRR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | Milli second (msec) | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected PR Interval (ΔPR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected QRS Interval (ΔQRS Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected QT Interval (ΔQT Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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|
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| Secondary | Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Baseline-corrected QTcF Interval (ΔQTcF Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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|
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| Secondary | Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval) | Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF). | The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time. | Posted | Mean | 95% Confidence Interval | msec | Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose |
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| Secondary | Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the pharmacokinetic (PK) of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Median | Full Range | Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Median | Full Range | Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Mean | Standard Deviation | Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol | Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol. | Posted | Median | Full Range | Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (Parent Drug Only) (CL/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol. | Posted | Mean | Standard Deviation | Liter/Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Parent Drug Only) (Vz/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol. | Posted | Mean | Standard Deviation | Liter | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Apparent Volume of Distribution at Steady State Following Extravascular Administration (Parent Drug Only) (Vss/F) for Verinurad and Allopurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol. | Posted | Mean | Standard Deviation | Liter | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for Verinurad and Oxypurinol | Assessment of the PK of verinurad and allopurinol in healthy participants. | The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose |
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| Secondary | Number of Participants With Adverse Events (AEs) | Examination of the safety and tolerability of verinurad and allopurinol. | The Safety Analysis Set included all participants who received at least 1 dose of study drug (verinurad, allopurinol, and placebo) and for whom any safety post-dose data were available. | Posted | Number | Participants | From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose) |
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| 0 |
| 22 |
| 0 |
| 22 |
| 8 |
| 22 |
| EG001 | Treatment B | Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol | 0 | 24 | 0 | 24 | 4 | 24 |
| EG002 | Treatment C | Participants received matching placebos for both verinurad and allopurinol | 0 | 23 | 0 | 23 | 5 | 23 |
| Somnolence | Nervous system disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Urine odour abnormal | Renal and urinary disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Medical device site reaction | General disorders | MedDRA Version 23.0 | Non-systematic Assessment |
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| Otitis externa | Infections and infestations | MedDRA Version 23.0 | Non-systematic Assessment |
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No unpublished information may be disclosed without prior written approval from AstraZeneca AB.
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| Day 1/ 12 h |
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|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| Day 1/ 1 h |
|
|
| Day 1/ 1.5 h |
|
|
| Day 1/ 2 h |
|
|
| Day 1/ 3 h |
|
|
| Day 1/ 4 h |
|
|
| Day 1/ 5 h |
|
|
| Day 1/ 6 h |
|
|
| Day 1/ 8 h |
|
|
| Day 1/ 12 h |
|
|
| Day 2/ 24 h |
|
|
| Day 2/ 36 h |
|
|
| Day 3/ 48 h |
|
|
| M1 |
|
|
| M8 |
|
|
| Allopurinol |
|
|
| Oxypurinol |
|
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
| M1 |
|
|
| M8 |
|
|
| Allopurinol |
|
|
| Oxypurinol |
|
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
| Allopurinol |
|
|
| Allopurinol |
|
|
| Allopurinol |
|
|
| Allopurinol |
|
|
| Title | Measurements |
|---|---|
|
| Any Serious adverse events (including events with outcome = death) |
|
| Any AE leading to discontinuation of study drug |
|
| Any AE leading to withdrawal from study |
|