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

NCT03857165 | Completed Phase 1 FDA Drug

• 2 other identifiers: SAP-001SAP001-1-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Gout, Hyperuricemia

Outcome Measures

Primary Outcomes (10)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Safety and tolerability of single escalating dose SAP-001

  5 days

• Cmax

  Maximum Plasma Concentration of SAP-001 in ng/mL

  5 days

• tmax

  Time to maximum concentration in hours

  5 days

• 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

  5 days

• 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

  24 hours

• λz

  Apparent terminal elimination rate constant

  5 days

• t1/2

  Terminal elimination phase half-life of SAP-001, calculated as ln(2)/λz

  5 days

• CL/F

  Total body clearance of SAP-001, calculated as Dose/AUC0-∞

  5 days

• Vz/F

  Volume of distribution of SAP-001

  5 days

• MRT

  Mean residence time in hours

  5 days

Secondary Outcomes (5)

• Serum uric acid (sUA) levels at various time points

  72 hours

• IL-1β

  24 hours

• IL-6

  24 hours

• IL-8

  24 hours

• TNFα

  24 hours

Study Arms (3)

Low dose SAP-001

EXPERIMENTAL

SAP-001 (Experimental drug) low dose versus placebo

Drug: SAP-001

Mid dose SAP-001

EXPERIMENTAL

SAP-001 (Experimental drug) mid dose versus placebo

Drug: SAP-001

High dose SAP-001

EXPERIMENTAL

SAP-001 (Experimental drug) high dose versus placebo

Drug: SAP-001

Interventions

SAP-001 DRUG

SAP-001 or placebo treatment in a 3:1 randomization ratio.

High dose SAP-001; Low dose SAP-001; Mid dose SAP-001

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanton Pharma Co., Ltd.: lead

Study Sites (3)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Avail - Accel Research Sites

DeLand, Florida, 32720, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

MeSH Terms

Conditions

Gout; Hyperuricemia

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single ascending dose with placebo control

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: February 27, 2019
• Study Start: September 24, 2018
• Primary Completion: June 2, 2019
• Study Completion: October 31, 2019
• Last Updated: October 14, 2021

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)