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A open label multi-center 3-period multidose, PK/PD and drug-drug interaction (DDI) study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of 7 days of treatment with two doses of dotinurad monotherapy, and to evaluate the effect of dotinurad, as monotherapy and in combination with allopurinol, versus allopurinol monotherapy, on the PK of each, and to assess the additive PD effects on serum uric acid and urinary urate excretion in U.S. patients with gout and hyperuricemia
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dotinurad 2mg | Experimental | dotinurad 2mg q.d. |
|
| dotinurad 4mg | Experimental | dotinurad 4mg q.d. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dotinurad | Drug | dotinurad alone |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Plasma Concentrations (Cmax) - Dotinurad PK Analysis | Peak plasma concentrations (Cmax) of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis | Day 7 |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-last) - Dotinurad PK Analysis | Area under the plasma concentration versus time curve (AUC 0-last)* of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis *area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated using linear-up log-down trapezoidal summation | Day 7 |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-Ï„) - Dotinurad PK Analysis | Area under the plasma concentration versus time curve (AUC 0-Ï„)* of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis *inter-dose interval area under the concentration-time curve from time 0 to the time of next dose, calculated using linear-up log-down trapezoidal summation | Day 7 |
| Time to Maximum Plasma Concentration (Tmax) - Dotinurad PK Analysis | Time to maximum plasma concentration (Tmax) of dotinurad, evaluated using median, for pharmacokinetics analysis | Day 7 |
| Terminal Half-life (T1/2) - Dotinurad PK Analysis | Terminal half-life (T1/2) of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis | Day 7 |
| Peak Plasma Concentration (Cmax) - Dotinurad DDI PK Analysis | Peak plasma concentration (Cmax) of dotinurad, evaluated using Geometric Least Squares Mean*, for DDI analysis * Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. |
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Inclusion Criteria:
1. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements.
2. Patients with a diagnosis of gout based on American College of Rheumatology criteria (1997). Patients must fulfill at least 3 of the following, with one of those 3 being (i) hyperuricemia.
More than one attack of acute arthritis
Maximum inflammation developed within 1 day
Monoarthritis attack
Redness observed over joints
First metatarsophalangeal joint painful or swollen
Unilateral first metatarsophalangeal joint attack
Unilateral tarsal joint attack
Tophus (proven or suspected)
Hyperuricemia.
Asymmetric swelling within a joint on x-ray
Subcortical cysts without erosions on x-ray
Monosodium urate monohydrate microcrystals on joint fluid during attack
Joint fluid culture negative for organisms during attack 3. The patient signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a patient fast for any laboratory evaluations.
4. Negative COVID-19 test by either PCR or rapid antigen test at screening and check-in prior to first period, and agrees to be compliant with all COVID-19 measures mandated by the CRU prior to screening/entry into the trial.
5. Male or female between 18 and 75 years of age (inclusive). To be eligible, females can be either of NCBP (confirmed by surgical history, medical history of twelve consecutive months of amenorrhea, or FSH levels) or females of childbearing potential must be on a reliable method of birth control and also have a negative urine human chorionic gonadotropin (hCG) pregnancy test results on the Study Day -1.
6. Screening serum uric acid level of ≥7 mg/dl.
a. If a patient is not on uric acid-lowering therapies (ULT) prior to screening, the required fasting sUA level is at least one ≥7 mg/dl during Screening b. If a patient is on ULT prior to screening, the required fasting sUA level is at least one =>7 mg/dl between Day -7 and Day -1 7. Screening liver enzymes (LFTs) <1.5x ULN. Total bilirubin <1x ULN. For patients with documented Gilbert Syndrome, total bilirubin ≤3 x ULN with direct bilirubin <1x ULN.
8. Screening renal function eGFR ≥ 60 mL/min/1.73m2. 9. Pre-dose hemoglobin should be within the normal range. 10. Body mass index (BMI) ≥ 18.5 and ≤ 40.0 (kg/m2) and a body weight of no less than 50 kg.
11. Medically healthy with no clinically significant screening results including but not limited to:
Laboratory profiles other than sUA
Urinalysis
Vital signs
Electrocardiograms (ECGs)
Physical examination 12. No use of tobacco or nicotine containing products (including smoking cessation products), for a minimum of 3 months prior to dosing.
Exclusion Criteria:
1. The subject has current or historical evidence of any clinically significant disease or condition that might complicate the subject's participation, or, in the opinion of the Investigator, may place the subject at an unacceptable risk as a participant in this trial, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study drug.
2. Patients with unstable angina, New York Heart Association Class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis within 1 year prior to Day 1.
3. QT interval corrected for heart rate according to Fridericia's formula >470 msec in females and >450 msec in males during Screening, confirmed by a repeat assessment.
4. History of or presence of kidney stones. 5. History of or presence of malignancy in the last 5 years other than treated cutaneous basal or squamous cell carcinoma.
6. Urological disorder not well controlled. 7. Peptic ulcer disease requiring active treatment. 8. Cannot safely discontinue uric acid-lowering medication 14 days prior to study start to 9 days after the last dose of study medication was administered.
9. Surgery within the past 90 days prior to dosing as determined by the Principal Investigator to be clinically relevant.
10. Use of agents that could confound serum uric acid analysis (eg, long-term use of salicylates >100 mg or use of losartan).
11. Patients with an acute gout flare during the screening period that had not resolved 1 week prior to the first dose of study.
12. Hypersensitivity or intolerance to allopurinol, dotinurad or colchicine. 13. Positive for HLA-B*58:01 allele 14. History or presence of alcoholism or chronic drug abuse within the past 2 years.
15. Psychiatric disorder or social situation that prevents compliance with the protocol.
16. Female patients who are pregnant or lactating. 17. Positive results for the urine drug /alcohol breath test/cotinine at check-in.
18. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), Hepatitis C antibodies (HCV).
19. Patient's semi-recumbent blood pressure is less than 90/40 mmHg or greater than 155/90 mmHg during Screening and Day -1.
20. Stable dose of medications for long-term conditions such as diabetes, high cholesterol, hypertension, asthma, etc. are allowed (provided that the patient has been on a stable dose for at least 30 days prior to Screening and is not expected to require dose adjustment during the study through 7 days post study).
21. Patient reports receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing, due to potential interactions with colchicine.
22. Patient has taken azathioprine, Imuran, or other medications that may interact with allopurinol within 1 month prior to study drug dosing 23. Participation in another clinical trial within 30 days of last IP administration or 5 half-lives (whichever is longer) of administration of any study drug evaluated in that trial prior to screening for this trial. Previous participation in a dotinurad trial is also exclusionary.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research of West Florida | Clearwater | Florida | 33765 | United States | ||
| Panax Clinical Research |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dotinurad 2mg | Period 1: dotinurad 2mg q.d. Period 2: dotinurad 2mg q.d. + allopurinol 300mg q.d. Period 3: allopurinol 300mg q.d. |
| FG001 | Dotinurad 4mg | Period 1: dotinurad 4mg q.d. Period 2: dotinurad 4mg q.d. + allopurinol 300mg q.d. Period 3: allopurinol 300mg q.d. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Dotinurad Monotherapy (7 Days) |
| |||||||||||||
| Period 2: Dotinurad+Allopurinol (7 Days) |
| |||||||||||||
| Period 3: Allopurinol Mono. (7 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dotinurad 2mg | Period 1: dotinurad 2mg q.d. Period 2: dotinurad 2mg q.d. + allopurinol 300mg q.d. Period 3: allopurinol 300mg q.d. |
| BG001 | Dotinurad 4mg | Period 1: dotinurad 4mg q.d. Period 2: dotinurad 4mg q.d. + allopurinol 300mg q.d. Period 3: allopurinol 300mg q.d. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at Screening |
| 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 | Peak Plasma Concentrations (Cmax) - Dotinurad PK Analysis | Peak plasma concentrations (Cmax) of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 7 |
|
|
Total treatment duration of 21 days
Per the Statistical Analysis Plan (SAP), adverse events are reported for the two treatment arms: Dotinurad 2 mg and Dotinurad 4 mg.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dotinurad 2mg Monotherapy | Period 1: dotinurad 2mg q.d. | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nihar Bhakta | Crystalys Therapeutics | 858-356-4740 | nbhakta@crystalystx.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 20, 2023 | Jul 16, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 12, 2023 | Jul 16, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006073 | Gout |
| D033461 | Hyperuricemia |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
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| ID | Term |
|---|---|
| C000706811 | dotinurad |
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| dotinurad + allopurinol |
| Drug |
dotinurad + allopurinol 300mg |
|
| allopurinol | Drug | allopurinol 300 mg alone |
|
| Day 7 and Day 14 |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-last) - Dotinurad DDI PK Analysis | Area under the plasma concentration versus time curve (AUC 0-last)* of dotinurad, evaluated using Geometric Least Squares Mean**, for DDI analysis *area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated using linear-up log-down trapezoidal summation ** Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | Day 7 and Day 14 |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-Ï„) - Dotinurad DDI PK Analysis | Area under the plasma concentration versus time curve (AUC 0-Ï„)* of dotinurad, evaluated using Geometric Least Squares Mean**, for DDI analysis *inter-dose interval area under the concentration-time curve from time 0 to the time of next dose, calculated using linear-up log-down trapezoidal summation ** Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | Day 7 and Day 14 |
| Terminal Half-life (T1/2) - Dotinurad DDI PK Analysis | Terminal half-life (T1/2) of dotinurad, evaluated using Least Squares Mean*, for DDI analysis *LS Mean, LS Mean Difference, CI, and p-value were calculated using ANOVA model on parameters (t1/2, CL/F, Vz/F, fe0-24, and CLR) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | Day 7 and Day 14 |
| Miami Lakes |
| Florida |
| 33014 |
| United States |
| Southwest Rheumatology Research | Mesquite | Texas | 75150 | United States |
| Endeavor Clinical Trials | San Antonio | Texas | 78240 | United States |
| NOT COMPLETED |
|
| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Sex | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race | Count of Participants | Participants |
|
| Baseline BMI | Mean | Standard Deviation | kg/m^2 |
|
| Participants |
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-last) - Dotinurad PK Analysis | Area under the plasma concentration versus time curve (AUC 0-last)* of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis *area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated using linear-up log-down trapezoidal summation | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 7 |
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-Ï„) - Dotinurad PK Analysis | Area under the plasma concentration versus time curve (AUC 0-Ï„)* of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis *inter-dose interval area under the concentration-time curve from time 0 to the time of next dose, calculated using linear-up log-down trapezoidal summation | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 7 |
|
|
|
| Primary | Time to Maximum Plasma Concentration (Tmax) - Dotinurad PK Analysis | Time to maximum plasma concentration (Tmax) of dotinurad, evaluated using median, for pharmacokinetics analysis | Posted | Median | Full Range | h | Day 7 |
|
|
|
| Primary | Terminal Half-life (T1/2) - Dotinurad PK Analysis | Terminal half-life (T1/2) of dotinurad, evaluated using geometric mean, for pharmacokinetics analysis | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Day 7 |
|
|
|
| Primary | Peak Plasma Concentration (Cmax) - Dotinurad DDI PK Analysis | Peak plasma concentration (Cmax) of dotinurad, evaluated using Geometric Least Squares Mean*, for DDI analysis * Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | DDI PK Dotinurad analysis population was 7/10 subjects in each arm.
| Posted | Geometric Least Squares Mean | 95% Confidence Interval | ng/mL | Day 7 and Day 14 |
|
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-last) - Dotinurad DDI PK Analysis | Area under the plasma concentration versus time curve (AUC 0-last)* of dotinurad, evaluated using Geometric Least Squares Mean**, for DDI analysis *area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated using linear-up log-down trapezoidal summation ** Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | DDI PK Dotinurad analysis population was 7/10 subjects in each arm.
| Posted | Geometric Least Squares Mean | 95% Confidence Interval | h*ng/mL | Day 7 and Day 14 |
|
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-Ï„) - Dotinurad DDI PK Analysis | Area under the plasma concentration versus time curve (AUC 0-Ï„)* of dotinurad, evaluated using Geometric Least Squares Mean**, for DDI analysis *inter-dose interval area under the concentration-time curve from time 0 to the time of next dose, calculated using linear-up log-down trapezoidal summation ** Geometric LS Mean, Geometric LS Mean Ratio, CI, and p-value were calculated using ANOVA model on log-transformed parameters (Areas, Cmax, and Ae0-24) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested, within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | DDI PK Dotinurad analysis population was 7/10 subjects in each arm.
| Posted | Geometric Least Squares Mean | 95% Confidence Interval | h*ng/mL | Day 7 and Day 14 |
|
|
|
|
| Primary | Terminal Half-life (T1/2) - Dotinurad DDI PK Analysis | Terminal half-life (T1/2) of dotinurad, evaluated using Least Squares Mean*, for DDI analysis *LS Mean, LS Mean Difference, CI, and p-value were calculated using ANOVA model on parameters (t1/2, CL/F, Vz/F, fe0-24, and CLR) considering treatment, dose group and treatment-by-dose group as fixed effects and subject nested within dose group as a random effect and was performed using SAS proc Mixed. If the treatment-by-dose group interaction was not significant at the 10% level, then it was dropped from the model. | DDI PK Dotinurad analysis population was 7/10 subjects in each arm.
| Posted | Least Squares Mean | 95% Confidence Interval | h | Day 7 and Day 14 |
|
|
|
|
| 10 |
| 0 |
| 10 |
| 2 |
| 10 |
| EG001 | Dotinurad 4mg Monotherapy | Period 1: dotinurad 4mg q.d. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG002 | Dotinurad 2mg + Allopurinol 300mg | Period 2: dotinurad 2mg q.d. + allopurinol 300mg q.d. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG003 | Dotinurad 4mg + Allopurinol 300mg | Period 2: dotinurad 4mg q.d. + allopurinol 300mg q.d. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG004 | Allopurinol 300mg Monotherapy (From Dotinurad 2mg Arm) | Period 3: allopurinol 300mg q.d. (from dotinurad 2mg arm) | 0 | 9 | 0 | 9 | 0 | 9 |
| EG005 | Allopurinol 300mg Monotherapy (From Dotinurad 4mg Arm) | Period 3: allopurinol 300mg q.d. (from dotinurad 4mg arm) | 0 | 9 | 0 | 9 | 1 | 9 |
| Constiptation | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Hypoesthesia | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA 26.0 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 26.0 | Non-systematic Assessment | One subject in dotinurad 4 mg treatment group had 4 AEs (Blood creatinine increased, Hepatic enzyme increased, Nausea, Vomiting). Subject withdrawn from the study not due Adverse Events. All AEs resolved. |
|
| Hepatic enzyme increased | Investigations | MedDRA 26.0 | Non-systematic Assessment | One subject in dotinurad 4 mg treatment group had 4 AEs (Blood creatinine increased, Hepatic enzyme increased, Nausea, Vomiting). Subject withdrawn from the study not due Adverse Events. All AEs resolved. |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment | One subject in dotinurad 4 mg treatment group had 4 AEs (Blood creatinine increased, Hepatic enzyme increased, Nausea, Vomiting). Subject withdrawn from the study not due Adverse Events. All AEs resolved. |
|
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Non-systematic Assessment | One subject in dotinurad 4 mg treatment group had 4 AEs (Blood creatinine increased, Hepatic enzyme increased, Nausea, Vomiting). Subject withdrawn from the study not due Adverse Events. All AEs resolved. |
|
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| D012216 |
| Rheumatic Diseases |
| D011686 | Purine-Pyrimidine Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| ANOVA | .111 | Geometric LS Mean Ratio | .878 | 2-Sided | 90 | .767 | 1.005 | Equivalence | For the assessment of DDI, the geometric mean ratios of key PK parameters (Cmax, AUC, Ae0-24) will be evaluated to determine the differences (if any) between combination therapy vs monotherapy of each drug, with tests of bioequivalence (BE) performed based on the 90% confidence interval being contained within the bioequivalence interval (80%, 125%). |
| ANOVA |
| .411 |
| Geometric LS Mean Ratio |
| .951 |
| 2-Sided |
| 90 |
| .853 |
| 1.062 |
| Equivalence |
For the assessment of DDI, the geometric mean ratios of key PK parameters (Cmax, AUC, Ae0-24) will be evaluated to determine the differences (if any) between combination therapy vs monotherapy of each drug, with tests of bioequivalence (BE) performed based on the 90% confidence interval being contained within the bioequivalence interval (80%, 125%). |
| ANOVA |
| .029 |
| Geometric LS Mean Ratio |
| 0.895 |
| 2-Sided |
| 90 |
| .830 |
| .965 |
| Equivalence |
For the assessment of DDI, the geometric mean ratios of key PK parameters (Cmax, AUC, Ae0-24) will be evaluated to determine the differences (if any) between combination therapy vs monotherapy of each drug, with tests of bioequivalence (BE) performed based on the 90% confidence interval being contained within the bioequivalence interval (80%, 125%). |
| 0.698 |
| LS Mean Difference |
| -0.371 |
| 2-Sided |
| 90 |
| -2.141 |
| 1.399 |
| Other |
The parameters t1/2, CL/F, Vz/F, fe0-24, and CLR will be evaluated by Proc Mixed without transformation. |