Study to Evaluate the Pharmacokinetics of Oral Sparsentan Suspension

NCT05562362 | Completed Phase 1 FDA Drug

• 1 other identifier: RTRX-RE021-102 (QSC200850)
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, open-label, randomized, single and multiple-dose, 3-way sequential study at 3 dose levels will be performed in healthy subjects. Subjects will be randomized to 1 of the 3 dose levels. In each dose level, subjects will be administered a single dose in the fasted state and then a single dose in the fed state, followed by 14 days of dosing to assess Pharmacokinetics (PK) following multiple dosing.

Conditions

Healthy Subjects

Keywords

Focal Segmental Glomerulosclerosis (FSGS); Immunoglobulin A Nephropathy (IgAN)

Outcome Measures

Primary Outcomes (9)

• Assessment of single-dose pharmacokinetics of sparsentan oral suspension dosed in fed and fasted states - Cmax

  Evaluation of, at minimum, the maximum concentration (Cmax) parameters for sparsentan following a single dose of sparsentan as an oral suspension in the fed or fasted state.

  Study Days 1 and 8

• Assessment of single-dose pharmacokinetics of sparsentan oral suspension dosed in fed and fasted states - AUC(0-last)

  Evaluation of, at minimum, the area under the concentration-time curve from dosing time 0 (AUC(0-last)) parameters for sparsentan following a single dose of sparsentan as an oral suspension in the fed or fasted state.

  Study Days 1 and 8

• Assessment of single-dose pharmacokinetics of sparsentan oral suspension dosed in fed and fasted - states - AUC(0-inf)

  Evaluation of, at minimum, the area under the concentration curve to infinite (AUC(0-inf)) time parameters for sparsentan following a single dose of sparsentan as an oral suspension in the fed or fasted state.

  Study Days 1 and 8

• Food effect on pharmacokinetics of sparsentan oral suspension dosed after standard high-fat - breakfast - Cmax

  Evaluation of the ratio, fed/fasted, for the Cmax

  Study Days 1 and 8

• Food effect on pharmacokinetics of sparsentan oral suspension dosed after standard high-fat - breakfast - AUC(0-last)

  Evaluation of the ratio, fed/fasted, for the AUC(0-last)

  Study Days 1 and 8

• Food effect on pharmacokinetics of sparsentan oral suspension dosed after standard high-fat breakfast - AUC(0-inf)

  Evaluation of the ratio, fed/fasted, for the AUC(0-inf)

  Study Days 1 and 8

• Multiple-dose pharmacokinetics of a sparsentan oral suspension dosed in the fed state - Cmax

  Evaluation of, at minimum, the following pharmacokinetics parameters for sparsentan following multiple doses of sparsentan as an oral suspension in the fed state: Cmax from a single dose for Study days 18 and 25 (Period 3, Days 7 and 14)

  Study Days 12 to 28

• Multiple-dose pharmacokinetics of a sparsentan oral suspension dosed in the fed state - AUC(0-24)

  Evaluation of, at minimum, the following pharmacokinetics parameters for sparsentan following multiple doses of sparsentan as an oral suspension in the fed state: Area under the plasma concentration-time curve over the last 24-h dosing interval (AUC(0-24)) from a single dose for Study days 18 and 25 (Period 3, Days 7 and 14)

  Study Days 12 to 28

• Multiple-dose pharmacokinetics of a sparsentan oral suspension dosed in the fed state - TCP (AUC(0-24)/AUC(0-inf)

  Evaluation of, at minimum, the following pharmacokinetics parameters for sparsentan following multiple doses of sparsentan as an oral suspension in the fed state: temporal change parameter (TCP) (AUC(0-24)/AUC(0-inf)) from a single dose for Study days 18 and 25 (Period 3, Days 7 and 14)

  Study Days 12 to 28

Secondary Outcomes (6)

• Assessment of safety and tolerability of sparsentan oral suspension - clinical chemistry, hematology and eGFR

  Study Days 1 to 28

• Assessment of Safety and tolerability of sparsentan oral suspension - vital sign (blood pressure)

  Study Days 1 to 28

• Assessment of Safety and tolerability of sparsentan oral suspension - vital sign (heart rate)

  Study Days 1 to 28

• Assessment of Safety and tolerability of sparsentan oral suspension - ECG

  Study Days 1 to 28

• Assessment of Safety and tolerability of sparsentan oral suspension - AEs

  2 to 28 days before Study Day 1 until 5 to 7 days post-final dose

Study Arms (3)

Fasted State

EXPERIMENTAL

Sparsentan will be administered in 3-dose level in healthy subjects. Subjects will be randomized to 1 of 3 dose levels (200mg, 400mg and 800 mg) and will receive a single dose of sparsentan in the fasted state on Period 1, Day 1 (Study Day 1)

Drug: RE-021, sparsentan

Fed State

EXPERIMENTAL

Sparsentan will be administered in 3-dose level in healthy subjects. Subjects will have a single dose of sparsentan (200mg, 400mg and 800 mg) in the fed state (high-fat breakfast) on Period 2, Day 1 (Study Day 8)

Drug: RE-021, sparsentan

Fed State - Multiple

EXPERIMENTAL

Sparsentan will be administered in 3-dose level in healthy subjects. Subjects will have multiple doses of sparsentan (200mg, 400mg and 800 mg) in the fed state on Period 3, Days 1 to 14 (Study days 12 to 25)

Drug: RE-021, sparsentan

Interventions

RE-021, sparsentan DRUG

RE-021, sparsentan - Subjects will be randomized 1 of 3 dose level

Fasted State; Fed State; Fed State - Multiple

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or healthy females of non-childbearing potential
• Between 18 and 55 years of age, inclusive, at time of signing informed consent
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent
• Must agree to adhere to the contraception requirements

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
• Subjects who are or are immediate family members of a study site employee or a sponsor employee
• Subjects who have previously been enrolled (dosed) in this study; subjects who have previously received sparsentan
• Evidence current SARS-CoV-2 infection
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
• A confirmed positive alcohol breath test at screening or admission
• Current smokers and those who have smoked within the last 3 months
• A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months
• Females of childbearing potential:
• A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone \[FSH\] concentration ≥40 IU/L)
• Subjects who are pregnant or lactating and subjects with pregnant or lactating partners. All women must have a negative pregnancy test at admission
• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening
• Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the investigator at screening

Sponsors & Collaborators

• Travere Therapeutics, Inc.: lead

Study Sites (1)

Travere Investigational Site

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental; Glomerulonephritis, IGA

Interventions

sparsentan

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: September 30, 2022
• Study Start: June 18, 2020
• Primary Completion: November 12, 2020
• Study Completion: November 12, 2020
• Last Updated: September 30, 2022

Record last verified: 2022-06

Locations

GB (1)