Chronic Kidney Disease
Conditions
Keywords
Pharmacokinetics, Cyclosporine, Rifampicin, Drug-Drug interaction, Organic anion transporting polypeptide (OATP1B) 1
Brief summary
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.
Detailed description
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): * A Screening Period (Visit 1); * A fixed sequence of 3 Treatment Periods during which subjects will be resident at the Clinical Unit from one day prior to administration of verinurad+allopurinol (Day -1) of Treatment Period 1 until the morning of Day 5 of the Treatment Period 2, and similarly for Treatment Period 3. There will be a washout period between Treatment Periods 2 and 3 dosing. The 3 Treatment Periods, include the washout period (Visits 2 to 3); * A Follow-up Visit, after the last administration of verinurad+allopurinol (Visit 4).
Interventions
DRUGVerinurad
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.
DRUGAllopurinol
The subjects will receive single oral dose of tablet allopurinol 300 mg on Day 1 of each treatment period under fasted condition.
DRUGCyclosporine
The subjects will receive single oral dose of soft capsule cyclosporine 600 mg on Day 1 of treatment period 2 under fasted condition.
DRUGRifampicin
The subjects will receive single oral dose of film coated tablets rifampicin 600 mg on Day 1 of treatment period 3 under fasted condition.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Fixed-sequence
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed and dated, written informed consent form prior to any study specific procedures. * Healthy male or female subjects aged 18 - 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. * Females must be either (1) Of non-childbearing potential, confirmed at Screening 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 sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. * Male subjects must adhere to the contraception methods. * Have a body mass index between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive). * Must be able to swallow multiple capsules/tablets.
Exclusion criteria
* History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study. * Subject has a positive test result for severe acute respiratory syndrome coronavirus 2 before dosing in Treatment Period 1. * Has clinical signs and symptoms consistent with coronavirus disease 2019 (COVID-19) infection, eg fever, dry cough, dyspnea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission. * History of severe COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated). * History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. * Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of verinurad. * Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at Screening (Visit 1) and on first admission (Day -1 in Treatment Period 1) as judged by the Investigator, including: 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: 1. Systolic blood pressure \<90 mmHg or \>140 mmHg and/or diastolic blood pressure \<50 mmHg or \>90 mmHg sustained for more than 10 minutes while resting in a supine position 2. Heart rate (resting, supine) \<50 or \>90 bpm * 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: 1. QTcF \> 450 ms or \< 340 ms or family history of long QT syndrome, 2. Any significant arrhythmia, 3. Conduction abnormalities, 4. Clinically significant PR(PQ) interval prolongation (\> 240 ms); intermittent second or third degree atrioventricular (AV) block, or AV dissociation, 5. Complete bundle branch block and/or QRS duration \> 120 ms. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | tmax of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | t½λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Days 1 to 5 (pre-dose and post-dose) | λz of verinurad, M1, M8, allopurinol and oxypurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Days 1 to 5 (pre-dose and post-dose) | CL/F for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Days 1 to 5 (pre-dose and post-dose) | MRTinf for verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Days 1 to 5 (pre-dose and post-dose) | Vss/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Days 1 to 5 (pre-dose and post-dose) | Vz/F of verinurad and allopurinol when verinurad+allopurinol administered alone or in combination with cyclosporine or rifampicin in each treatment period. |
| Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | Days 1 to 5 (pre-dose and post-dose) | 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. |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | From screening (Day -28 to -2) until Follow-up or Early Termination (7-14 days after last verinurad dose) | Assessment the safety and tolerability of verinurad and allopurinol in combination with cyclosporine or rifampicin |
Countries
Germany
Participant flow
Recruitment details
The study was conducted between 10-Sep-2020 and 23-Nov-2020 in Germany.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 34.6 Years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 2 / 14 | 10 / 14 | 2 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 1 / 13 |
Outcome results
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | 90.25 h*ng/mL | Geometric Coefficient of Variation 50.76 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | 215.1 h*ng/mL | Geometric Coefficient of Variation 30.94 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Verinurad | 138.0 h*ng/mL | Geometric Coefficient of Variation 26.11 |
Comparison: Statistical comparison of AUCinf90% CI: [207.6, 273.8]
Comparison: Statistical comparison of AUCinf90% CI: [129.1, 171.7]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | 79.67 h*ng/mL | Geometric Coefficient of Variation 50.43 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | 208.6 h*ng/mL | Geometric Coefficient of Variation 30.07 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Area Under the Plasma Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUClast) for Verinurad | 133.4 h*ng/mL | Geometric Coefficient of Variation 26.59 |
Comparison: Statistical comparison of AUClast90% CI: [229.8, 298.1]
Comparison: Statistical comparison of AUClast90% CI: [142.8, 186.6]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | 13.30 ng/mL | Geometric Coefficient of Variation 53.48 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | 33.96 ng/mL | Geometric Coefficient of Variation 29.39 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Maximum Observed Plasma Peak Concentration (Cmax) for Verinurad | 26.09 ng/mL | Geometric Coefficient of Variation 32.28 |
Comparison: Statistical comparison of Cmax90% CI: [208.7, 312.3]
Comparison: Statistical comparison of Cmax90% CI: [154, 233.1]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Verinurad | 92.30 Liter/Hours | Standard Deviation 43.4 |
| Period 1: Verinurad + Allopurinol | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Allopurinol | 77.12 Liter/Hours | Standard Deviation 17.51 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Verinurad | 36.32 Liter/Hours | Standard Deviation 10.44 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Allopurinol | 78.09 Liter/Hours | Standard Deviation 16.07 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Verinurad | 55.99 Liter/Hours | Standard Deviation 14 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Verinurad and Allopurinol | Allopurinol | 73.29 Liter/Hours | Standard Deviation 14.24 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 3982 h*ng/mL | Geometric Coefficient of Variation 22.69 |
| Period 1: Verinurad + Allopurinol | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 79.80 h*ng/mL | Geometric Coefficient of Variation 41.26 |
| Period 1: Verinurad + Allopurinol | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 62.02 h*ng/mL | Geometric Coefficient of Variation 45.44 |
| Period 1: Verinurad + Allopurinol | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 86.23 h*ng/mL | Geometric Coefficient of Variation 45.69 |
| Period 1: Verinurad + Allopurinol | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 100700 h*ng/mL | Geometric Coefficient of Variation 17.92 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 38.02 h*ng/mL | Geometric Coefficient of Variation 45.54 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 192.2 h*ng/mL | Geometric Coefficient of Variation 31.45 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 314.4 h*ng/mL | Geometric Coefficient of Variation 39.75 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 3914 h*ng/mL | Geometric Coefficient of Variation 20.05 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 95080 h*ng/mL | Geometric Coefficient of Variation 18.15 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 98460 h*ng/mL | Geometric Coefficient of Variation 18.59 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 4163 h*ng/mL | Geometric Coefficient of Variation 19.24 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 118.4 h*ng/mL | Geometric Coefficient of Variation 23.88 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 48.81 h*ng/mL | Geometric Coefficient of Variation 45.08 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Area Under Plasma Concentration-time Curve From Zero to 24 Hours Post-dose AUC(0-24) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 242.9 h*ng/mL | Geometric Coefficient of Variation 29.33 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Allopurinol | 3982 h*ng/mL | Geometric Coefficient of Variation 22.69 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Oxypurinol | 196500 h*ng/mL | Geometric Coefficient of Variation 28.48 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Allopurinol | 3914 h*ng/mL | Geometric Coefficient of Variation 20.06 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Oxypurinol | 181900 h*ng/mL | Geometric Coefficient of Variation 24.23 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Allopurinol | 4163 h*ng/mL | Geometric Coefficient of Variation 19.24 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUCinf for Allopurinol and Oxypurinol | Oxypurinol | 195500 h*ng/mL | Geometric Coefficient of Variation 24.85 |
Comparison: Statistical comparison of AUCinf for allopurinol90% CI: [91.26, 105.9]
Comparison: Statistical comparison of AUCinf for allopurinol90% CI: [93.72, 109.2]
Comparison: Statistical comparison of AUCinf for oxypurinol90% CI: [95.02, 103.5]
Comparison: Statistical comparison of AUCinf for oxypurinol90% CI: [92.15, 100.1]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M1 | 119.5 h*ng/mL | Geometric Coefficient of Variation 50.57 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M8 | 110.3 h*ng/mL | Geometric Coefficient of Variation 46.28 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M1 | 348.7 h*ng/mL | Geometric Coefficient of Variation 39.87 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M8 | 60.98 h*ng/mL | Geometric Coefficient of Variation 60.46 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M1 | 264.9 h*ng/mL | Geometric Coefficient of Variation 30.04 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUCinf for Verinurad Metabolites: M1 and M8 | M8 | 77.35 h*ng/mL | Geometric Coefficient of Variation 43.24 |
Comparison: Statistical comparison of AUCinf for metabolite: M190% CI: [260.6, 326.8]
Comparison: Statistical comparison of Cmax for metabolite: M190% CI: [192, 242.4]
Comparison: Statistical comparison of AUCinf for metabolite: M890% CI: [47.19, 64.83]
Comparison: Statistical comparison of AUCinf for metabolite: M890% CI: [57.99, 80.39]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Allopurinol | 3889 h*ng/mL | Geometric Coefficient of Variation 23.01 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Oxypurinol | 183600 h*ng/mL | Geometric Coefficient of Variation 24.64 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Allopurinol | 3821 h*ng/mL | Geometric Coefficient of Variation 19.78 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Oxypurinol | 170600 h*ng/mL | Geometric Coefficient of Variation 22.29 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Allopurinol | 4080 h*ng/mL | Geometric Coefficient of Variation 19.24 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUClast for Allopurinol and Oxypurinol | Oxypurinol | 182100 h*ng/mL | Geometric Coefficient of Variation 21.72 |
Comparison: Statistical comparison of AUClast for allopurinol90% CI: [91.1, 106]
Comparison: Statistical comparison of AUClast for allopurinol90% CI: [93.99, 109.8]
Comparison: Statistical comparison of AUClast for oxypurinol90% CI: [94.5, 101.7]
Comparison: Analysis of variance of log transformed PK parameter with treatment and participant as fixed effects90% CI: [92.61, 99.48]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M1 | 111.6 h*ng/mL | Geometric Coefficient of Variation 51.84 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M8 | 101.8 h*ng/mL | Geometric Coefficient of Variation 45.17 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M1 | 341.9 h*ng/mL | Geometric Coefficient of Variation 40.12 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M8 | 51.95 h*ng/mL | Geometric Coefficient of Variation 52.12 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M1 | 260.6 h*ng/mL | Geometric Coefficient of Variation 30.7 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of AUClast for Verinurad Metabolites: M1 and M8 | M8 | 73.23 h*ng/mL | Geometric Coefficient of Variation 44.42 |
Comparison: Statistical comparison of AUClast for metabolite: M190% CI: [273.3, 343.6]
Comparison: Statistical comparison of AUClast for metabolite: M190% CI: [202.1, 255.8]
Comparison: Statistical comparison of AUClast for metabolite: M890% CI: [43.8, 59.45]
Comparison: Statistical comparison of AUClast for metabolite: M890% CI: [60.21, 82.44]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Allopurinol | 1947 ng/mL | Geometric Coefficient of Variation 51.09 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Oxypurinol | 6064 ng/mL | Geometric Coefficient of Variation 18.15 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Allopurinol | 1457 ng/mL | Geometric Coefficient of Variation 33.2 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Oxypurinol | 5876 ng/mL | Geometric Coefficient of Variation 18.24 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Allopurinol | 1597 ng/mL | Geometric Coefficient of Variation 38.55 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Cmax for Allopurinol and Oxypurinol | Oxypurinol | 6051 ng/mL | Geometric Coefficient of Variation 20.41 |
Comparison: Statistical comparison of Cmax for allopurinol90% CI: [59.42, 94.26]
Comparison: Statistical comparison of Cmax for allopurinol90% CI: [63.88, 102.7]
Comparison: Statistical comparison of Cmax for oxypurinol90% CI: [92.11, 101.8]
Comparison: Statistical comparison of Cmax for oxypurinol90% CI: [94.36, 104]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M1 | 17.24 ng/mL | Geometric Coefficient of Variation 50.28 |
| Period 1: Verinurad + Allopurinol | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M8 | 15.57 ng/mL | Geometric Coefficient of Variation 40.02 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M8 | 3.839 ng/mL | Geometric Coefficient of Variation 59.94 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M1 | 47.14 ng/mL | Geometric Coefficient of Variation 34.05 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M8 | 6.002 ng/mL | Geometric Coefficient of Variation 48.53 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Geometric Mean Ratio of Cmax for Verinurad Metabolites: M1 and M8 | M1 | 48.70 ng/mL | Geometric Coefficient of Variation 31.47 |
Comparison: Statistical comparison of Cmax for metabolite: M190% CI: [227.9, 328.1]
Comparison: Statistical comparison of Cmax for metabolite: M190% CI: [228.7, 332.7]
Comparison: Statistical comparison of Cmax for metabolite: M890% CI: [19.15, 31.72]
Comparison: Statistical comparison of Cmax for metabolite: M890% CI: [29.18, 49.03]
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 1.210 Hours | Standard Deviation 0.1427 |
| Period 1: Verinurad + Allopurinol | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 18.25 Hours | Standard Deviation 8.326 |
| Period 1: Verinurad + Allopurinol | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 20.31 Hours | Standard Deviation 12.02 |
| Period 1: Verinurad + Allopurinol | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 18.04 Hours | Standard Deviation 10.81 |
| Period 1: Verinurad + Allopurinol | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 23.19 Hours | Standard Deviation 6.361 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 21.90 Hours | Standard Deviation 24.13 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 14.73 Hours | Standard Deviation 13 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 13.05 Hours | Standard Deviation 9.455 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 1.261 Hours | Standard Deviation 0.279 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 22.36 Hours | Standard Deviation 4.977 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 23.76 Hours | Standard Deviation 5.641 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 1.170 Hours | Standard Deviation 0.1052 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 15.03 Hours | Standard Deviation 12.54 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 14.89 Hours | Standard Deviation 6.948 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration Time Curve (t½λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 12.52 Hours | Standard Deviation 7.01 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Verinurad | 21.28 Hours | Geometric Coefficient of Variation 49.56 |
| Period 1: Verinurad + Allopurinol | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Allopurinol | 2.316 Hours | Geometric Coefficient of Variation 30.1 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Verinurad | 11.05 Hours | Geometric Coefficient of Variation 50.07 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Allopurinol | 2.713 Hours | Geometric Coefficient of Variation 22.05 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Verinurad | 12.60 Hours | Geometric Coefficient of Variation 36.82 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) for Verinurad and Allopurinol | Allopurinol | 2.496 Hours | Geometric Coefficient of Variation 20.04 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M1:verinurad | 1.324 Ratio | Geometric Coefficient of Variation 35.14 |
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M8:verinurad | 1.222 Ratio | Geometric Coefficient of Variation 27.85 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M1:verinurad | 1.621 Ratio | Geometric Coefficient of Variation 23.8 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M8:verinurad | 0.2834 Ratio | Geometric Coefficient of Variation 56.73 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M1:verinurad | 1.919 Ratio | Geometric Coefficient of Variation 22.89 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) AUCinf Ratios for M1 and M8: Verinurad | M8:verinurad | 0.5604 Ratio | Geometric Coefficient of Variation 36.82 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M1:verinurad | 1.400 Ratio | Geometric Coefficient of Variation 28.68 |
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M8:verinurad | 1.278 Ratio | Geometric Coefficient of Variation 26.07 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M1:verinurad | 1.639 Ratio | Geometric Coefficient of Variation 24.98 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M8:verinurad | 0.2491 Ratio | Geometric Coefficient of Variation 54.22 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M1:verinurad | 1.955 Ratio | Geometric Coefficient of Variation 23.27 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) AUClast Ratios for M1 and M8: Verinurad | M8:verinurad | 0.5491 Ratio | Geometric Coefficient of Variation 39.93 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M1: verinurad | 1.296 Ratio | Geometric Coefficient of Variation 36.79 |
| Period 1: Verinurad + Allopurinol | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M8: verinurad | 1.171 Ratio | Geometric Coefficient of Variation 30.12 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M1: verinurad | 1.388 Ratio | Geometric Coefficient of Variation 28.01 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M8: verinurad | 0.1130 Ratio | Geometric Coefficient of Variation 56.62 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M1: verinurad | 1.866 Ratio | Geometric Coefficient of Variation 24.09 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Metabolite:Parent (MP) Cmax Ratios for M1 and M8: Verinurad | M8: verinurad | 0.2300 Ratio | Geometric Coefficient of Variation 52.89 |
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
Time frame: From screening (Day -28 to -2) until Follow-up or Early Termination (7-14 days after last verinurad dose)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE | 2 Participants |
| Period 1: Verinurad + Allopurinol | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of study drug | 0 Participants |
| Period 1: Verinurad + Allopurinol | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any SAE | 0 Participants |
| Period 1: Verinurad + Allopurinol | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to withdrawal from study | 0 Participants |
| Period 1: Verinurad + Allopurinol | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE with outcome = death | 0 Participants |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to withdrawal from study | 1 Participants |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE | 10 Participants |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE with outcome = death | 0 Participants |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any SAE | 0 Participants |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of study drug | 1 Participants |
| Period 3: Verinurad + Allopurinol + Rifampicin | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE with outcome = death | 0 Participants |
| Period 3: Verinurad + Allopurinol + Rifampicin | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to withdrawal from study | 0 Participants |
| Period 3: Verinurad + Allopurinol + Rifampicin | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of study drug | 0 Participants |
| Period 3: Verinurad + Allopurinol + Rifampicin | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any AE | 3 Participants |
| Period 3: Verinurad + Allopurinol + Rifampicin | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Any SAE | 1 Participants |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 0.5770 1/Hours | Geometric Coefficient of Variation 12.51 |
| Period 1: Verinurad + Allopurinol | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 0.04163 1/Hours | Geometric Coefficient of Variation 46.83 |
| Period 1: Verinurad + Allopurinol | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 0.03842 1/Hours | Geometric Coefficient of Variation 49.71 |
| Period 1: Verinurad + Allopurinol | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 0.04293 1/Hours | Geometric Coefficient of Variation 47.35 |
| Period 1: Verinurad + Allopurinol | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 0.03086 1/Hours | Geometric Coefficient of Variation 26.32 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 0.04497 1/Hours | Geometric Coefficient of Variation 93.89 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 0.06101 1/Hours | Geometric Coefficient of Variation 82.31 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 0.06518 1/Hours | Geometric Coefficient of Variation 71.96 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 0.5616 1/Hours | Geometric Coefficient of Variation 21.69 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 0.03169 1/Hours | Geometric Coefficient of Variation 22.14 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 0.02990 1/Hours | Geometric Coefficient of Variation 23.34 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 0.5950 1/Hours | Geometric Coefficient of Variation 9.54 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 0.05557 1/Hours | Geometric Coefficient of Variation 62.04 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 0.05133 1/Hours | Geometric Coefficient of Variation 48.74 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Terminal Elimination Rate Constant (λz) of Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 0.06417 1/Hours | Geometric Coefficient of Variation 61.89 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 0.50 Hours |
| Period 1: Verinurad + Allopurinol | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 4.52 Hours |
| Period 1: Verinurad + Allopurinol | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 4.03 Hours |
| Period 1: Verinurad + Allopurinol | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 4.02 Hours |
| Period 1: Verinurad + Allopurinol | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 4.00 Hours |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 8.00 Hours |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 5.00 Hours |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 5.98 Hours |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 1.00 Hours |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 4.00 Hours |
| Period 3: Verinurad + Allopurinol + Rifampicin | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Oxypurinol | 3.00 Hours |
| Period 3: Verinurad + Allopurinol + Rifampicin | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Allopurinol | 1.00 Hours |
| Period 3: Verinurad + Allopurinol + Rifampicin | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | Verinurad | 4.00 Hours |
| Period 3: Verinurad + Allopurinol + Rifampicin | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M8 | 5.00 Hours |
| Period 3: Verinurad + Allopurinol + Rifampicin | Time to Reach Peak or Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol and Oxypurinol | M1 | 4.00 Hours |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Verinurad | 2455 Liters | Standard Deviation 1337 |
| Period 1: Verinurad + Allopurinol | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Allopurinol | 133.5 Liters | Standard Deviation 27.94 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Verinurad | 721.8 Liters | Standard Deviation 574.6 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Allopurinol | 137.9 Liters | Standard Deviation 20.16 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Verinurad | 1153 Liters | Standard Deviation 758.7 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on the Terminal Phase) (Vz/F) of Verinurad and Allopurinol | Allopurinol | 122.6 Liters | Standard Deviation 18.84 |
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.
Time frame: Days 1 to 5 (pre-dose and post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Verinurad + Allopurinol | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Verinurad | 1768 Liters | Geometric Coefficient of Variation 53.52 |
| Period 1: Verinurad + Allopurinol | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Allopurinol | 174.5 Liters | Geometric Coefficient of Variation 41.88 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Verinurad | 385.2 Liters | Geometric Coefficient of Variation 52.45 |
| Period 2: Verinurad + Allopurinol + Cyclosporine | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Allopurinol | 208.0 Liters | Geometric Coefficient of Variation 17.39 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Allopurinol | 179.9 Liters | Geometric Coefficient of Variation 30.55 |
| Period 3: Verinurad + Allopurinol + Rifampicin | Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vss/F) of Verinurad and Allopurinol | Verinurad | 685.0 Liters | Geometric Coefficient of Variation 38.16 |