Placebo Controlled, Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAP-001 in Gout Patients

NCT04040816 | Completed Phase 2 FDA Drug

• 1 other identifier: SAP001-1-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase II, Multicenter, Randomized, Double-blind, Placebo controlled, Multiple Dose study to evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAP-001 in Gout Patients with Hyperuricemia.

Conditions

Gout; Hyperuricemia

Outcome Measures

Primary Outcomes (12)

• Incidence of Treatment-Emergent Adverse Events

  Assess the safety and tolerability of multiple ascending doses of oral SAP-001 over 28 days compared to placebo

  28 days

• Cmax

  Maximum observed plasma concentration

  28 days

• tmax

  Time to maximum observed plasma concentration

  28 days

• AUC0-t

  Area under the plasma concentration-time curve from time 0 to time t

  28 days

• AUC0-24h

  Area under the plasma concentration-time curve from time 0 until 24 hours postdose

  28 days

• AUC0-∞

  Area under the plasma concentration-time curve from time 0 extrapolated to infinity

  28 days

• λz

  Apparent terminal elimination rate constant

  28 days

• t½

  Terminal elimination phase half-life

  28 days

• CL/F

  Total body clearance

  28 days

• Vz/F

  Volume of distribution

  28 days

• sUA

  Serum urate concentration, change from baseline, and percent change from baseline

  28 days

• Creatinine

  Creatinine levels, change from baseline, and percent change from baseline

  28 days

Secondary Outcomes (2)

• Urate Lowering Effect

  28 days

• Inflammation markers including cytokines IL-1β, IL-6, IL-8, and TNFα

  28 days

Study Arms (4)

Dose A

EXPERIMENTAL

Dose A SAP-001 versus placebo

Drug: SAP-001

Dose B

EXPERIMENTAL

Dose B SAP-001 versus placebo

Drug: SAP-001

Dose C

EXPERIMENTAL

Dose C SAP-001 versus placebo

Drug: SAP-001

Dose D (allopurinol patients)

EXPERIMENTAL

Dose D SAP-001 versus placebo in gout patients who remain on allopurinol

Drug: SAP-001

Interventions

SAP-001 DRUG

SAP-001 or placebo treatment in a 4:1 randomization ratio

Dose A; Dose B; Dose C; Dose D (allopurinol patients)

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 ≥ 18 and ≤ 75 years of age.
• Body mass index (BMI) ≥ 19 and ≤ 42 kg/m2 at screening.
• sUA levels ≥ 7.5 mg/dL during screening and at check-in (Day -1).
• Patients must meet the American College of Rheumatology scoring criteria for the classification of primary gout (Neogi et al 2015).
• Patients must be able to take gout flare prophylaxis with colchicine 0.6 mg QD throughout the study as the primary method to prevent disease flare. If colchicine is not tolerated or contraindicated, naproxen 250 mg BID with or without H2 antagonists will be employed as a second line gout flare prophylactic agent. Gout flare prophylaxis will be initiated at the Day -1 visit in patients who are sUA-lowering agent naïve. For patients that discontinue an sUA-lowering agent(s) (ie, washout from current therapy) during the screening period, gout flare prophylaxis should be initiated at the time of discontinuation of the sUA-lowering agent(s).
• Is a nonsmoker or light smoker (smokes fewer than 10 cigarettes per day).
• Female patients either will 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 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, except those with documented surgical hysterectomy in medical history, will have a negative urine pregnancy test result prior to enrollment in the study.
• Male patients either will 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.
• Cohorts 1 through 3:
• Patients who are not taking any UA-lowering medications within 2 weeks prior to the dose of study drug. Patients may discontinue sUA-lowering agents (ie, washout from current therapy) during the screening period. In the cases of a patient who must discontinue sUA-lowering agents or a patient not previously taking sUA-lowering agents during the screening period, gout flare prophylaxis should be initiated with colchicine 0.6 mg QD as the primary method to prevent disease flare and be continued during the study period. If colchicine is not tolerated or contraindicated, naproxen 250 mg BID with or without H2 antagonists will be employed as a second line gout flare prophylactic agent.
• Cohort 4:
• Patient has been on a stable dose of allopurinol as existing urate-lowering therapy for at least 3 months prior to Day 1.

You may not qualify if:

• Female patient is pregnant, planning to get pregnant, or lactating/breastfeeding.
• Has a history or presence of 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 rate (eGFR) ≤ 60 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey et al 2009; National Institute of Diabetes and Digestive and Kidney Diseases, Estimating Glomerular Filtration Rate) at screening.
• History of stomach or intestinal surgery (except 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 test for human immunodeficiency virus (HIV).
• Positive test for hepatitis B virus or hepatitis C virus (HCV) consistent with current infection. Confirmatory tests will be allowed at the discretion of the investigator to rule out false positives.
• Clinically significant abnormal liver function test at screening or check-in (Day -1), defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5 × upper limit of normal (ULN) or total bilirubin \> ULN; or a history of CS 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 if it is a result of a prescribed medication from their physician) at screening or check-in (Day -1).
• History of a gout flare that is resolved within 14 days prior to the first dose of study drug on Day 1 (exclusive of chronic synovitis/arthritis). If a gout flare occurs during screening, patients may be rescreened after a period of at least 14 days has passed following the flare.
• Has a known hypersensitivity to URAT1 inhibitors, XOIs, or related compounds.
• Receipt of any other investigational product within 30 days prior to the first dose of study drug on Day 1 or planning to take an investigational agent during the study.
• Use of drugs or nutrients known to significantly modulate cytochrome P450 (CYP)3A activity starting from 14 days prior to the first dose of study drug on Day 1 until EOS (any strong or moderate inhibitors or inducers of CYP3A4, 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 EOS.
• Has donated or lost a significant volume (\> 500 mL) of blood or plasma within 30 days prior to check-in (Day -1).

Sponsors & Collaborators

• Shanton Pharma Co., Ltd.: lead

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Anaheim Clinical Trials (ACT)

Anaheim, California, 92801, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

Advanced Clinical Research

Meridian, Idaho, 83642, United States

Location

Vince & Associates Clinical Research, Inc.

Overland Park, Kansas, 66212, United States

Location

M3 Wake Research, Inc

Raleigh, North Carolina, 27612, 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

• Celina Cabale-Scholl, DPT, RN

  Shanton Pharma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: August 1, 2019
• Study Start: January 1, 2019
• Primary Completion: August 1, 2020
• Study Completion: August 30, 2020
• Last Updated: November 5, 2021

Record last verified: 2021-11

Locations

US (6)