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

Primary Purpose

Gout, Hyperuricemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SAP-001
Sponsored by
Shanton Pharma Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gout, Hyperuricemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Anaheim Clinical Trials, LLC
  • Avail - Accel Research Sites
  • High Point Clinical Trials Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Low dose SAP-001

Mid dose SAP-001

High dose SAP-001

Arm Description

SAP-001 (Experimental drug) low dose versus placebo

SAP-001 (Experimental drug) mid dose versus placebo

SAP-001 (Experimental drug) high dose versus placebo

Outcomes

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Safety and tolerability of single escalating dose SAP-001
Cmax
Maximum Plasma Concentration of SAP-001 in ng/mL
tmax
Time to maximum concentration in hours
AUC0-t
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
AUC0-24h
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
λz
Apparent terminal elimination rate constant
t1/2
Terminal elimination phase half-life of SAP-001, calculated as ln(2)/λz
CL/F
Total body clearance of SAP-001, calculated as Dose/AUC0-∞
Vz/F
Volume of distribution of SAP-001
MRT
Mean residence time in hours

Secondary Outcome Measures

Serum uric acid (sUA) levels at various time points
Serum uric acid (sUA) levels in mg/dL at various time points after oral administration of ascending single dose of SAP-001 or placebo
IL-1β
Inflammatory cytokine IL-1β in pg/mL
IL-6
Inflammatory cytokine IL-6 in pg/mL
IL-8
Inflammatory cytokine IL-8 in pg/mL
TNFα
Inflammatory cytokine TNFα in pg/mL

Full Information

First Posted
October 18, 2018
Last Updated
October 13, 2021
Sponsor
Shanton Pharma Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03857165
Brief Title
Placebo Controlled, Dose Escalation Study to Evaluate Safety, Pharmacokinetics & Efficacy of SAP-001 in Gout Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
September 24, 2018 (Actual)
Primary Completion Date
June 2, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanton Pharma Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout, Hyperuricemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Single ascending dose with placebo control
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low dose SAP-001
Arm Type
Experimental
Arm Description
SAP-001 (Experimental drug) low dose versus placebo
Arm Title
Mid dose SAP-001
Arm Type
Experimental
Arm Description
SAP-001 (Experimental drug) mid dose versus placebo
Arm Title
High dose SAP-001
Arm Type
Experimental
Arm Description
SAP-001 (Experimental drug) high dose versus placebo
Intervention Type
Drug
Intervention Name(s)
SAP-001
Intervention Description
SAP-001 or placebo treatment in a 3:1 randomization ratio.
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Safety and tolerability of single escalating dose SAP-001
Time Frame
5 days
Title
Cmax
Description
Maximum Plasma Concentration of SAP-001 in ng/mL
Time Frame
5 days
Title
tmax
Description
Time to maximum concentration in hours
Time Frame
5 days
Title
AUC0-t
Description
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
Time Frame
5 days
Title
AUC0-24h
Description
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
Time Frame
24 hours
Title
λz
Description
Apparent terminal elimination rate constant
Time Frame
5 days
Title
t1/2
Description
Terminal elimination phase half-life of SAP-001, calculated as ln(2)/λz
Time Frame
5 days
Title
CL/F
Description
Total body clearance of SAP-001, calculated as Dose/AUC0-∞
Time Frame
5 days
Title
Vz/F
Description
Volume of distribution of SAP-001
Time Frame
5 days
Title
MRT
Description
Mean residence time in hours
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Serum uric acid (sUA) levels at various time points
Description
Serum uric acid (sUA) levels in mg/dL at various time points after oral administration of ascending single dose of SAP-001 or placebo
Time Frame
72 hours
Title
IL-1β
Description
Inflammatory cytokine IL-1β in pg/mL
Time Frame
24 hours
Title
IL-6
Description
Inflammatory cytokine IL-6 in pg/mL
Time Frame
24 hours
Title
IL-8
Description
Inflammatory cytokine IL-8 in pg/mL
Time Frame
24 hours
Title
TNFα
Description
Inflammatory cytokine TNFα in pg/mL
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, between 18 and 75 years of age, inclusive. Body mass index (BMI) between 19 and 42 kg/m^2 at screening, inclusive. Serum uric acid (sUA) levels ≥7.5 mg/dL at screening. Patients must meet all the American College of Rheumatology scoring criteria for the classification of primary gout (Neogi et al., 2015). Patients who are not taking any UA-lowering medications 1 month prior to the dose of study drug. Is a nonsmoker or light smoker (smokes fewer than 10 cigarettes per day). 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. 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. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements. Exclusion Criteria: 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. 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) History of stomach or intestinal surgery (except that cholecystectomy, appendectomy, and/or hernia repair will be allowed). 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. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCV) antibody. 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. 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). History of a gout flare that is resolved within 14 days prior to first treatment with study drug (exclusive of chronic synovitis/arthritis). Has a known hypersensitivity to URAT1 inhibitors, XOIs, or related compounds. 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. 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. 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. Participated in strenuous exercise from 48 hours prior to Check-in (Day -1) or during the study through the final end of study assessment. Has donated or lost a significant volume (>500 mL) of blood or plasma within 30 days prior to Check-in (Day -1). Malignancy within 5 years of the screening visit. 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. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M Hill, MD
Organizational Affiliation
Accel Research Sites (Avail Clinical Research)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Melanie Fein
Organizational Affiliation
High Point Clinical Trials Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Winkle
Organizational Affiliation
Anaheim Clinical Trials, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anaheim Clinical Trials, LLC
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Avail - Accel Research Sites
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
High Point Clinical Trials Center
City
High Point
State/Province
North Carolina
ZIP/Postal Code
27265
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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