Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Parexel | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
This Phase 1 study aims to quantify the effects of cyclosporine, a broad transporter inhibitor, and rifampicin, an OATP1B1/3 inhibitor, on verinurad pharmacokinetics (PK). The study is conducted in accordance with Food and Drug Administration guidance on Clinical Drug Interaction Studies, 2020. Verinurad will be developed as a fixed combination since it will always be administered together with allopurinol.
This Phase 1 study will be an open-label, 3-period, 3-treatment, fixed-sequence study in healthy subjects (males and females of non-childbearing potential), performed at a single Clinical Unit.
The study will comprise of the following periods (visits):
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Verinurad + allopurinol | Experimental | The subjects will receive single oral dose of verinurad 7.5 mg and allopurinol 300 mg under fasted condition. |
|
| Verinurad + allopurinol + cyclosporine | Experimental | The subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and cyclosporine 600 mg under fasted condition. |
|
| Verinurad + allopurinol + rifampicin | Experimental | The subjects will receive single oral dose of verinurad 7.5 mg, allopurinol 300 mg and rifampicin 600 mg under fasted condition. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Verinurad | Drug | The subjects will receive single oral dose of extended release capsule verinurad 7.5 mg on Day 1 of each treatment period under fasted condition. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad Cmax ratio of geometric mean of test treatment (verinurad+allopurinol with [cyclosporine or rifampicin], relative to reference treatment (verinurad+allopurinol alone) in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUCinf ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUClast ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. Cmax ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
Not provided
Inclusion Criteria:
(ii) Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Exclusion Criteria:
Alanine aminotransferase >1.5 × Upper limit of normal (ULN) Aspartate aminotransferase >1.5 × ULN Bilirubin (total) >1.5 × ULN Gamma glutamyl transpeptidase >1.5 × ULN If any of these tests are out of range, the test can be repeated once at the Screening Visit at the discretion of the Investigator.
Any clinically significant abnormal findings in vital signs at Screening Visit and/or on admission (Day -1 in Treatment Period 1) to the Clinical Unit, including, but not limited to, any of the following:
Any clinically significant abnormalities on 12-lead electrocardiogram at Screening Visit, as judged by the Investigator, including, but not limited to any of the following:
Any positive result at Screening Visit for serum hepatitis B surface antigen or anti-hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus antibody.
Suspicion or known Gilbert's and/or Lesch-Nyhan syndrome
History of hypersensitivity to drugs with a similar chemical structure or class to verinurad, allopurinol, cyclosporine or rifampicin or excipients.
Subjects who wear soft contact lenses (due to possible staining from rifampicin), unless the subject is prepared to refrain from wearing soft lenses throughout Treatment Period 3 until after the last PK sample collection.
Women of childbearing potential.
Carrier of the Human leukocyte antigen B*58:01 allele.
Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing in the US or EU) within 30 days or within 5 half-lives (whichever is longer) of the first administration of verinurad in this study.
Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to Novel uric acid transporter 1 transporter inhibitor & xanthine oxidase inhibitor.
Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.
Positive screen for drugs of abuse, cotinine or alcohol at Screening or on each admission to the Clinical Unit.
Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of verinurad.
Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
Known or suspected history of alcohol or drug 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 of alcohol per day for women.
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 or would likely be unable to refrain from the use of caffeine-containing beverages during in-house stay at the investigational site.
Involvement of any AstraZeneca, Parexel or Clinical Unit employee or their close relatives.
Judgment by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
Subjects who are vegans or have medical dietary restrictions.
Subjects who cannot communicate reliably with the Investigator and/or are not able to read, speak and understand the German language.
Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 |
Not provided
| Label | URL |
|---|---|
| CSP and SAP redacted | View source |
Not provided
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.
Not provided
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 rerefer 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.
Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
The study was conducted between 10-Sep-2020 and 23-Nov-2020 in Germany.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study | Participants received treatments in 3 different treatment periods. Single oral dose of extended release capsule verinurad 7.5 mg, and tablet allopurinol 300 mg, in all 3 treatment periods, under fasted conditions. Along with, participants also received single oral dose of soft capsule of cyclosporine 600 mg in treatment period 2, and film coated tablets of rifampicin 600 mg in treatment period 3 respectively, under fasted condition. There was a washout period of 14 days between treatment periods 2 and 3 dosing. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analysis set included all participants who received at least 1 dose of study drug, and for whom safety post-dose data were available, were included in the safety analysis for the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Participants received treatments in 3 different treatment periods. Single oral dose of extended release capsule verinurad 7.5 mg, and tablet allopurinol 300 mg, in all 3 treatment periods, under fasted conditions. Along with, participants also received single oral dose of soft capsule of cyclosporine 600 mg in treatment period 2, and film coated tablets of rifampicin 600 mg in treatment period 3 respectively, under fasted condition. There was a washout period of 14 days between treatment periods 2 and 3 dosing. |
| 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 | Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad Cmax ratio of geometric mean of test treatment (verinurad+allopurinol with [cyclosporine or rifampicin], relative to reference treatment (verinurad+allopurinol alone) in each treatment period. | The pharmacokinetic (PK) analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
From screening (Day -28 to -2) until Follow-up or Early Termination (7-14 days after last verinurad dose)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period 1: Verinurad + Allopurinol | Participants received a single oral dose extended release capsule of verinurad 7.5 mg, and tablet of allopurinol 300 mg, under fasted conditions from days 1 to 5. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bone contusion | Injury, poisoning and procedural complications | MedDRA 23.0. | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Feeling hot | General disorders | MedDRA 23.0. | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Not provided
| 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 19, 2020 | Jun 10, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000628929 | verinurad |
| D000493 | Allopurinol |
| D016572 | Cyclosporine |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Fixed-sequence
Not provided
Not provided
Not provided
Not provided
| Allopurinol | Drug | The subjects will receive single oral dose of tablet allopurinol 300 mg on Day 1 of each treatment period under fasted condition. |
|
| Cyclosporine | Drug | The subjects will receive single oral dose of soft capsule cyclosporine 600 mg on Day 1 of treatment period 2 under fasted condition. |
|
|
| Rifampicin | Drug | The subjects will receive single oral dose of film coated tablets rifampicin 600 mg on Day 1 of treatment period 3 under fasted condition. |
|
|
| Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 |
Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. AUCinf ratio of geometric means of test treatment, relative to reference treatment in each treatment period. |
| Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. AUClast ratio of geometric means of test treatment, relative to reference treatment in each treatment period is reported. | Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. Cmax ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. AUCinf ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | Days 1 to 5 (pre-dose and post-dose) |
| Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. AUClast ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | Days 1 to 5 (pre-dose and post-dose) |
| Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | AUC(0-24) of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | tmax of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | t½λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | CL/F for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | MRTinf for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Vss/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Vz/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) Cmax ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) AUCinf ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) AUClast ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | Days 1 to 5 (pre-dose and post-dose) |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Assessment the safety and tolerability of verinurad and allopurinol in combination with cyclosporine or rifampicin | From screening (Day -28 to -2) until Follow-up or Early Termination (7-14 days after last verinurad dose) |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Period 2: Verinurad + Allopurinol + Cyclosporine | Participants received a single oral dose extended release capsule verinurad 7.5 mg, tablet allopurinol 300 mg, and soft capsule cyclosporine 600 mg, under fasted conditions from days 1 to 5. |
| OG002 | Period 3: Verinurad + Allopurinol + Rifampicin | Participants received a single oral dose extended release capsule verinurad 7.5 mg, tablet allopurinol 300 mg, and film coated tablets rifampicin, under fasted conditions from days 1 to 5. |
|
|
|
| Primary | Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUCinf ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Primary | Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad. Verinurad AUClast ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. Cmax ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. AUCinf ratio of geometric means of test treatment, relative to reference treatment in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | Evaluation of a single dose of cyclosporine or rifampicin on the PK of verinurad metabolites M1 and M8. AUClast ratio of geometric means of test treatment, relative to reference treatment in each treatment period is reported. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. Cmax ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. AUCinf ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Evaluation of a single dose of cyclosporine or rifampicin on the PK of allopurinol and oxypurinol. AUClast ratio of geometric means of test geometric means of test treatment, relative to reference treatment in each treatment period is reported. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
|
| Secondary | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | AUC(0-24) of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | tmax of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Median | Full Range | Hours | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | t½λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Mean | Standard Deviation | Hours | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/Hours | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | CL/F for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Mean | Standard Deviation | Liter/Hours | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | MRTinf for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Vss/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Vz/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Mean | Standard Deviation | Liters | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) Cmax ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) AUCinf ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | Metabolite:parent (MP) AUClast ratios for M1 and M8: verinurad when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. | The PK analysis set included all participants in the safety analysis set who received a verinurad+allopurinol dose and who had at least 1 quantifiable post-dose plasma concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Days 1 to 5 (pre-dose and post-dose) |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Assessment the safety and tolerability of verinurad and allopurinol in combination with cyclosporine or rifampicin | The safety analysis set included all participants who received at least 1 dose of study drug, and for whom safety post-dose data were available, were included in the safety analysis for the study. | Posted | Count of Participants | Participants | From screening (Day -28 to -2) until Follow-up or Early Termination (7-14 days after last verinurad dose) |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 2 |
| 14 |
| EG001 | Period 2: Verinurad + Allopurinol + Cyclosporine | Participants received a single oral dose extended release capsule verinurad 7.5 mg, tablet allopurinol 300 mg, and soft capsule cyclosporine 600 mg, under fasted conditions from days 1 to 5. | 0 | 14 | 0 | 14 | 10 | 14 |
| EG002 | Period 3: Verinurad + Allopurinol + Rifampicin | Participants received a single oral dose extended release capsule verinurad 7.5 mg, tablet allopurinol 300 mg, and film coated tablets rifampicin, under fasted conditions from days 1 to 5. | 0 | 14 | 1 | 13 | 2 | 13 |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 23.0. | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Vessel puncture site haematoma | General disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 23.0. | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0. | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0. | Non-systematic Assessment |
|
Not provided
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
Statistical comparison of AUCinf |
| Geometric Mean Ratio (%) |
| 148.9 |
| 2-Sided |
| 90 |
| 129.1 |
| 171.7 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
Statistical comparison of AUClast |
| Geometric Mean Ratio (%) |
| 163.2 |
| 2-Sided |
| 90 |
| 142.8 |
| 186.6 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
|
Statistical comparison of Cmax for metabolite: M1 |
| Geometric Mean Ratio (%) |
| 275.9 |
| 2-Sided |
| 90 |
| 228.7 |
| 332.7 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of Cmax for metabolite: M8 | Geometric Mean Ratio (%) | 24.65 | 2-Sided | 90 | 19.15 | 31.72 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of Cmax for metabolite: M8 | Geometric Mean Ratio (%) | 37.82 | 2-Sided | 90 | 29.18 | 49.03 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
|
Statistical comparison of Cmax for metabolite: M1 |
| Geometric Mean Ratio (%) |
| 215.8 |
| 2-Sided |
| 90 |
| 192.0 |
| 242.4 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUCinf for metabolite: M8 | Geometric Mean Ratio (%) | 55.31 | 2-Sided | 90 | 47.19 | 64.83 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUCinf for metabolite: M8 | Geometric Mean Ratio (%) | 68.28 | 2-Sided | 90 | 57.99 | 80.39 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
|
Statistical comparison of AUClast for metabolite: M1 |
| Geometric Mean Ratio (%) |
| 227.4 |
| 2-Sided |
| 90 |
| 202.1 |
| 255.8 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUClast for metabolite: M8 | Geometric Mean Ratio (%) | 51.03 | 2-Sided | 90 | 43.80 | 59.45 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUClast for metabolite: M8 | Geometric Mean Ratio (%) | 70.45 | 2-Sided | 90 | 60.21 | 82.44 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
Statistical comparison of Cmax for allopurinol |
| Geometric Mean Ratio (%) |
| 80.99 |
| 2-Sided |
| 90 |
| 63.88 |
| 102.7 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of Cmax for oxypurinol | Geometric Mean Ratio (%) | 96.86 | 2-Sided | 90 | 92.11 | 101.8 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of Cmax for oxypurinol | Geometric Mean Ratio (%) | 99.07 | 2-Sided | 90 | 94.36 | 104.0 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
|
Statistical comparison of AUCinf for allopurinol |
| Geometric Mean Ratio (%) |
| 101.2 |
| 2-Sided |
| 90 |
| 93.72 |
| 109.2 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUCinf for oxypurinol | Geometric Mean Ratio (%) | 99.16 | 2-Sided | 90 | 95.02 | 103.5 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUCinf for oxypurinol | Geometric Mean Ratio (%) | 96.05 | 2-Sided | 90 | 92.15 | 100.1 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
|
|
Statistical comparison of AUClast for allopurinol |
| Geometric Mean Ratio (%) |
| 101.6 |
| 2-Sided |
| 90 |
| 93.99 |
| 109.8 |
Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) |
| Other |
Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Statistical comparison of AUClast for oxypurinol | Geometric Mean Ratio (%) | 98.05 | 2-Sided | 90 | 94.50 | 101.7 | Pairwise comparisons of Test 1/ reference (verinurad+allopurinol+cyclosporine/ verinurad+allopurinol alone) | Other | Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects |
| Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects | Geometric Mean Ratio (%) | 95.98 | 2-Sided | 90 | 92.61 | 99.48 | Pairwise comparisons of Test 2/ reference (verinurad+allopurinol+rifampicin/ verinurad+allopurinol alone) | Other |
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
|
| M8 |
|
| Allopurinol |
|
| Oxypurinol |
|
|
|
|
|
|
|
|
| Title | Measurements |
|---|---|
|
| Any SAE |
|
| Any AE leading to discontinuation of study drug |
|
| Any AE leading to withdrawal from study |
|