PK and Safety Evaluation Study of SAP-001 in Adult Subjects With Normal and Impaired Renal Function

A Phase 1, Open-Label, Parallel-Group, Single-Dose Adaptive Study to Evaluate the Safety and Pharmacokinetics of SAP-001 in Adult Subjects With Normal and Impaired Renal Function

This is a multicenter, open-label, non-randomized, parallel-group, single-dose, 2-part, adaptive study in which up to approximately 32 adult subjects will be enrolled in one of 4 groups (8 subjects per group) with varying degrees of renal function.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperuricemia; Gout
• Intervention / Treatment: Drug: SAP-001

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All subjects:

1. Provision of signed and dated informed consent form (ICF)
2. Subject is, as stated and in the opinion of the Investigator, willing and able to comply with the study drug regimen and all other protocol and study procedures and requirements, and is available for the duration of the study
3. Adult male or female
4. Subject is willing to comply with the contraceptive requirements as defined in APPENDIX 6
5. Aged at least 18 years but not older than 80 years
6. BMI ≥ 18.5 kg/m2 and < 42.0 kg/m2 at the time of Screening.
7. Light-, non- or ex-smoker (A light smoker is defined as someone using 10.0 nicotine units [1 unit = 1 cigarette] or less per day for at least 90 days prior to study drug administration. An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to study drug administration)

8. Having suitable venous access for blood sampling

   Subjects with Normal Renal Function (Group 4):

9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the laboratory tests, physical examination (including vital signs) and/or ECG, as determined by an Investigator
10. Normal renal function with estimated glomerular filtration rate (eGFR) ≥ 90 mL/minute at Screening

11. Must match to the pooled mean age (± 10 years), BMI (within 20%) and sex (ratio should be similar) of mild, moderate (if applicable), and severe (if applicable) renal impaired subjects

    Subjects with mild, moderate, or severe renal impairment (Groups 1, 2 and 3, respectively):

12. Considered clinically stable in the opinion of an Investigator
13. Presence of mild renal impairment (eGFR ≥ 60 and < 90 mL/min), moderate renal impairment (eGFR ≥ 30 and < 60 mL/min) or severe renal impairment (eGFR≥ 15 and < 30 mL/min) at Screening. Renal impairment should be stable for at least 1 month prior to Screening (change in eGFR should not be more than 25%).

Note: The Investigator can order a repeat of eGFR if it is determined that the initial value is inconsistent with the historical values for a particular subject

Exclusion Criteria:

All subjects:

1. Female who is lactating
2. Female who is pregnant according to the pregnancy test at Screening or prior to study drug administration
3. History of significant hypersensitivity to SAP-001 or any related products (including excipients of the formulation) as well as severe hypersensitivity reactions (like angioedema) to any drugs
4. Positive screening results to HIV Ag/Ab Combo and Hepatitis B surface antigen (HBsAg)
5. Positive reflex test for Hepatitis C antibody (positive Hepatitis C antibody is allowed if HCV RNA is not detected)
6. Presence or history of any disorder that could interfere with completion of the study based on the opinion of an Investigator
7. Intake of SAP-001 or any Investigational Product (IP) in the 28 days (or 5 times the half-life of the drug, whichever is longer) prior to study drug administration
8. Have urinary incontinence without catheterization
9. Reception of blood products within 3 months prior to study drug administration
10. Donation of 50 mL or more of blood in the 28 days prior to Screening
11. Donation of 500 mL or more of blood within 56 days prior to Screening.
12. Donation of plasma within 2 weeks prior to Screening or platelets within 6 weeks prior to Screening

13. Inclusion in a previous group for this clinical study

    Subjects with Normal Renal Function (Group 4):

14. Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects
15. History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
16. Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
17. Presence of out-of-range cardiac interval (eg, QTcF > 440 msec) based on the mean of the triplicate ECG values at Screening or other clinically significant ECG abnormalities, unless deemed non-significant by an Investigator
18. Positive test result for alcohol and/or drugs of abuse at Screening or prior to study drug administration
19. Seated blood pressure below 90/60 mmHg at Screening and prior to dosing
20. Seated blood pressure higher than 140/90 mmHg at Screening and prior to dosing
21. Seated pulse rate less than 40 beats per minutes (bpm) or more than 100 bpm at Screening and prior to dosing
22. Any clinically significant illness in the 28 days prior to study drug administration
23. Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to study drug administration that, in the opinion of an Investigator, would put into question the status of the participant as healthy
24. Use of St. John's wort in the 28 days prior to study drug administration
25. Use of over-the-counter drugs and natural health products (eg, herbal remedies) in the 14 days (or 5 times the half-life of the drug, whichever is longer) prior to study drug administration

26. Use of any enzyme-modifying drugs, or drugs with effects on membrane transporters, including any strong cytochrome P450 3A4 and P-glycoprotein inducers and inhibitors in the previous 28 days prior to study drug administration

    Subjects with Renal Impairment (Groups 1, 2 and 3):

27. History of renal transplant
28. Seated blood pressure below 100/50 mmHg at Screening and prior to dosing
29. Seated blood pressure higher than 180/100 mmHg at Screening and prior to dosing
30. Seated pulse rate less than 50 bpm or more than 110 bpm at Screening and prior to dosing
31. History or presence, in the opinion of an Investigator, of significant clinically unstable respiratory, cardiovascular, pulmonary, hepatic, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
32. Presence of poorly controlled Type 1 or Type 2 diabetes as defined by hemoglobin A1c > 10%
33. Presence of clinically significant physical examination, laboratory test, or ECG finding that, in the opinion of an Investigator and/or Sponsor, may interfere with any aspect of study conduct or interpretation of results
34. Subjects requiring treatment for renal impairment or other chronic disease (eg, well-controlled diabetes, hypertension) must be on a stable treatment plan (medicines, doses, and regimens) for at least 14 days (except insulin) prior to study drug administration and during the entire study. Small adjustments in the dosages of some concomitant medications may be permitted during the study and will be discussed on a case-by-case basis. In all cases, the subjects' treatment history must be reviewed and their enrollment must be agreed to by both an Investigator and the Sponsor's Medical Monitor
35. Positive screening of alcohol and/or drugs of abuse at Screening or prior to study drug administration unless results can be explained by a prescription medication
36. Concurrent use of medications known to affect the elimination of serum creatinine (eg, trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors of renal tubular secretion (eg, probenecid) within 30 days prior to study drug administration or anticipated need for these therapies through to the last PK sample of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild renal impairment; Subjects with mild renal impairment	Drug: SAP-001; a single oral dose of SAP-001
Experimental: Moderate renal impairment; Subjects with moderate renal impairment	Drug: SAP-001; a single oral dose of SAP-001
Experimental: Severe renal impairment; Subjects with severe renal impairment(Optional)	Drug: SAP-001; a single oral dose of SAP-001
Experimental: Healthy match; Matched healthy subjects with normal renal function	Drug: SAP-001; a single oral dose of SAP-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum observed concentration (Cmax)	The primary PK endpoints	day 8
AUC from time 0 to time of last quantifiable sample (AUC0-T)	The primary PK endpoints	day 8
apparent clearance (CL/F)	The primary PK endpoints	day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to maximum concentration (Tmax)	Plasma PK parameters	day 8
AUC from time 0 extrapolated to infinity (AUC0-∞)	Plasma PK parameters	day 8
terminal elimination half-life (Thalf)	Plasma PK parameters	day 8
volume of distribution (Vz/F)	Plasma PK parameters	day 8
Ae(0-T) (amount excreted)	Urine PK parameters:	day 8
Fraction of dose excreted in urine (fe)	Urine PK parameters:	day 8
CLr (renal clearance)	Urine PK parameters:	day 8

Collaborators and Investigators

• Sponsor: Shanton Pharma Pte. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): January 17, 2025
• Study Completion (Estimated): April 28, 2025

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Estimated): December 11, 2024

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Hyperuricemia; Renal Insufficiency
• Other Study ID Numbers: SAP-001-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No