Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Placebo Controlled, Dose Escalation Study to Evaluate Safety, Pharmacokinetics & Efficacy of SAP-001 in Gout Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03857165
Recruitment Status : Active, not recruiting
First Posted : February 27, 2019
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Shanton Pharma Co., Ltd.

Brief Summary:
This is a Phase I, Multicenter, Randomized, Double-blind, Placebo controlled, Dose-escalation study to evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAP-001 in Gout Patients with Hyperuricemia. The study will be single dose ascending cohorts across three doses with a placebo control arm.

Condition or disease Intervention/treatment Phase
Gout, Hyperuricemia Drug: SAP-001 Phase 1

Detailed Description:
A total of 24 eligible adult subjects will be randomized in a 3:1 randomization ratio into two blinded treatment groups in the three dose cohorts with matching placebo arm. The duration of the observation would be 5 days for each subject with a single SAP-001 dosing to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of oral SAP-001 (once daily) in adults gout patients with hyperuricemia.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single ascending dose with placebo control
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo Controlled, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAP-001 in Gout Patients With Hyperuricemia
Actual Study Start Date : September 24, 2018
Actual Primary Completion Date : June 2, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout

Arm Intervention/treatment
Experimental: Low dose SAP-001
SAP-001 (Experimental drug) low dose versus placebo
Drug: SAP-001
SAP-001 or placebo treatment in a 3:1 randomization ratio.

Experimental: Mid dose SAP-001
SAP-001 (Experimental drug) mid dose versus placebo
Drug: SAP-001
SAP-001 or placebo treatment in a 3:1 randomization ratio.

Experimental: High dose SAP-001
SAP-001 (Experimental drug) high dose versus placebo
Drug: SAP-001
SAP-001 or placebo treatment in a 3:1 randomization ratio.




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 5 days ]
    Safety and tolerability of single escalating dose SAP-001

  2. Cmax [ Time Frame: 5 days ]
    Maximum Plasma Concentration of SAP-001 in ng/mL

  3. tmax [ Time Frame: 5 days ]
    Time to maximum concentration in hours

  4. AUC0-t [ Time Frame: 5 days ]
    Area under the concentration-time curve from time 0 to time t, calculated using the linear trapezoidal rule for increasing values, and the log trapezoidal rule for decreasing values

  5. AUC0-24h [ Time Frame: 24 hours ]
    Area under the concentration-time curve from time 0 until 24 hours post dose, calculated using the linear trapezoidal rule for increasing values, and the log trapezoidal rule for decreasing values

  6. λz [ Time Frame: 5 days ]
    Apparent terminal elimination rate constant

  7. t1/2 [ Time Frame: 5 days ]
    Terminal elimination phase half-life of SAP-001, calculated as ln(2)/λz

  8. CL/F [ Time Frame: 5 days ]
    Total body clearance of SAP-001, calculated as Dose/AUC0-∞

  9. Vz/F [ Time Frame: 5 days ]
    Volume of distribution of SAP-001

  10. MRT [ Time Frame: 5 days ]
    Mean residence time in hours


Secondary Outcome Measures :
  1. Serum uric acid (sUA) levels at various time points [ Time Frame: 72 hours ]
    Serum uric acid (sUA) levels in mg/dL at various time points after oral administration of ascending single dose of SAP-001 or placebo

  2. IL-1β [ Time Frame: 24 hours ]
    Inflammatory cytokine IL-1β in pg/mL

  3. IL-6 [ Time Frame: 24 hours ]
    Inflammatory cytokine IL-6 in pg/mL

  4. IL-8 [ Time Frame: 24 hours ]
    Inflammatory cytokine IL-8 in pg/mL

  5. TNFα [ Time Frame: 24 hours ]
    Inflammatory cytokine TNFα in pg/mL



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, between 18 and 75 years of age, inclusive.
  2. Body mass index (BMI) between 19 and 42 kg/m^2 at screening, inclusive.
  3. Serum uric acid (sUA) levels ≥7.5 mg/dL at screening.
  4. Patients must meet all the American College of Rheumatology scoring criteria for the classification of primary gout (Neogi et al., 2015).
  5. Patients who are not taking any UA-lowering medications 1 month prior to the dose of study drug.
  6. Is a nonsmoker or light smoker (smokes fewer than 10 cigarettes per day).
  7. Female patients cannot be pregnant or lactating/breast-feeding and will either be postmenopausal (female patients who state they are postmenopausal should have had cessation of menses for>1 year and have serum follicle stimulating hormone [FSH] levels >40 mIU/mL and serum estradiol < 20 pg/mL or a negative estrogen test), surgically sterile (including bilateral tubal ligation, salpingectomy [with or without oophorectomy], surgical hysterectomy, or bilateral oophorectomy [with or without hysterectomy]) for at least 3 months prior to Screening, or will agree to use, from the time of Check-in (Day -1) until 90 days following the last dose of study drug, the following forms of contraception: double-barrier method, hormonal contraceptives, barrier with spermicide, diaphragm or cervical cap with spermicide, intrauterine device, oral, implantable, or injectable contraceptives, or a sterile sexual partner. All female patients will have a negative urine or serum pregnancy test result prior to enrollment in the study.
  8. Male patients will either be surgically sterile or agree to use, from the time of Check-in (Day -1) until 90 days following the last dose of study drug, the following forms of contraception: male condom with spermicide and a female partner who is sterile or agrees to use hormonal contraceptives, female condom with spermicide, diaphragm or cervical cap with spermicide, intrauterine device, oral, implantable, or injectable contraceptives. Male patients will refrain from sperm donation from the time of Check-in (Day -1) until 90 days following the last dose of study drug.
  9. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.

Exclusion Criteria:

  1. Has a history or presence of clinically significant (CS) cardiovascular, renal, pulmonary, hepatic, gallbladder or biliary tract, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, which in the Investigator's opinion would not be suitable for the study.
  2. Serum creatinine level > 1.5 mg/dL and/or estimated glomerular filtration (eGFR) by the Modification of Diet in Renal Disease (MDRD) rate ≤60 mL/min/1.73 m2 at screening. The MDRD formula is: GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
  3. History of stomach or intestinal surgery (except that cholecystectomy, appendectomy, and/or hernia repair will be allowed).
  4. History of prescription drug abuse, illicit drug use, or alcohol abuse according to medical history within 6 months prior to the Screening visit or any alcohol use for at least 48 hours prior to dosing on Day 1.
  5. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCV) antibody.
  6. Clinically significant abnormal liver function test at screening or Check-in (Day -1), defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT)>1.5 times upper limit of normal (ULN) or total bilirubin >ULN; or a history of clinically significant acute or chronic hepatitis (including infectious, metabolic, autoimmune, genetic, ischemic, or other forms), hepatocirrhosis, or hepatic tumors.
  7. Positive screen for alcohol or drugs of abuse (except for patients with a positive drug screen test if it is a result of a prescribed medication from their physician) at Screening and Check-in (Day -1).
  8. History of a gout flare that is resolved within 14 days prior to first treatment with study drug (exclusive of chronic synovitis/arthritis).
  9. Has a known hypersensitivity to URAT1 inhibitors, XOIs, or related compounds.
  10. Receipt of any other investigational product within 30 days prior to the dose of study drug on Day 1or planning to take an investigational agent during the study.
  11. Concomitant use of or treatment with any prescription drugs, herbal products, vitamins, minerals, and over-the-counter medications within 14 days prior to Check in (Day -1). Exceptions may be made on a case by case basis following discussion and agreement between the Investigator and the Sponsor.
  12. Use of any drugs or nutrients known to modulate cytochrome P450 (CYP)3A activity or any strong or moderate inhibitors or inducers of CYP3A4, starting from 14 days prior to dose administration on Day 1 until the final end of study assessments, including but not limited to the following: inhibitors such as ketoconazole, miconazole, itraconazole, fluconazole, atazanavir, erythromycin, clarithromycin, ranitidine, cimetidine, verapamil, and diltiazem and inducers such as rifampicin, rifabutin, glucocorticoids, carbamazepine, phenytoin, phenobarbital, and St. John's wort.
  13. Participated in strenuous exercise from 48 hours prior to Check-in (Day -1) or during the study through the final end of study assessment.
  14. Has donated or lost a significant volume (>500 mL) of blood or plasma within 30 days prior to Check-in (Day -1).
  15. Malignancy within 5 years of the screening visit.
  16. Has problems understanding the protocol requirements, instructions, study related restrictions, and/or problems understanding the nature, scope, and potential consequences of participating in this clinical study.
  17. Is unlikely to comply with the protocol requirements, instructions, and/or study related restrictions (e.g., uncooperative attitude, unavailable for follow up call, and/or improbability of completing the clinical study).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03857165


Locations
Layout table for location information
United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92801
United States, Florida
Avail - Accel Research Sites
DeLand, Florida, United States, 32720
United States, North Carolina
High Point Clinical Trials Center
High Point, North Carolina, United States, 27265
Sponsors and Collaborators
Shanton Pharma Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: John M Hill, MD Accel Research Sites (Avail Clinical Research)
Principal Investigator: Melanie Fein High Point Clinical Trials Center
Principal Investigator: Peter Winkle Anaheim Clinical Trials, LLC

Layout table for additonal information
Responsible Party: Shanton Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT03857165     History of Changes
Other Study ID Numbers: SAP-001
SAP001-1-001 ( Other Identifier: SHANTON PHARMA CO., LTD. )
First Posted: February 27, 2019    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gout
Hyperuricemia
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes