None listed
Conditions
Brief summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, characterized by the progressive formation and enlargement of fluid-filled cysts in the kidneys, which can lead to chronic kidney disease and ultimately end-stage renal disease (ESRD). Investigational Product: GV-100 Dose Form: Suspension Route of Administration: Oral This randomized, placebo-controlled study is designed to evaluate safety and tolerability, as well as pharmacokinetics (PK) and pharmacodynamics (PD), and is conducted in two parts: Part 1 (Single Ascending Dose [SAD]), Part 2 (Multiple Ascending Dose [MAD]).
Interventions
This is a first-in-human, multi-part clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), food effect, and drug–drug interaction (DDI) potential of GV-100 following oral administration in healthy participants. The study is divided into four parts: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), Food Effect (FE), and Drug–Drug Interaction (DDI).
Subjects will be confined on site and observed during dosing, and IP usage will be documented.
Part 1: Sin
This is a first-in-human, multi-part clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), food effect, and drug–drug interaction (DDI) potential of GV-100 following oral administration in healthy participants. The study is divided into four parts: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), Food Effect (FE), and Drug–Drug Interaction (DDI). Subjects will be confined on site and observed during dosing, and IP usage will be documented. Part 1: Single Ascending Dose (SAD) The SAD part will assess the safety, tolerability, and PK of single oral doses of GV-100 at 150 mg, 400 mg, 800 mg, and 1200 mg. Approximately 32 participants will be enrolled across 4 cohorts, with 8 participants per cohort randomized in a 3:1 ratio (6 receiving GV-100 and 2 receiving placebo). Participants will be screened between Day -28 and Day -2, admitted on Day -1, and confined through completion of assessments on Day 2, with a follow-up visit on Day 8 (±1 day). Each cohort will use a staggered dosing strategy, with 2 sentinel participants (1 active, 1 placebo) dosed first, followed by the remaining participants at least 24 hours later, subject to review of safety data and approval by the Principal Investigator or delegate. Part 2: Multiple Ascending Dose (MAD) The MAD part will be initiated after the Safety Review Committee (SRC) reviews and approves safety, tolerability, and PK data from a SAD dose level higher than the planned MAD starting dose. GV-100 will be administered orally at 400 mg, 800 mg, and 1200 mg. Approximately 24 participants will be enrolled across 3 cohorts, with 8 participants per cohort randomized in a 3:1 ratio (6 receiving GV-100 and 2 receiving placebo). Participants will be screened between Day -28 and Day -2, admitted on Day -1, and confined through completion of assessments on Day 15, followed by a Day 21 (±1 day) follow-up. The SRC will review safety, tolerability, and PK data for each dose level and decide on dose escalation, de-escalation, repetition, or termination. Dose escalation will be guided by PK exposure limits, ensuring predicted exposures do not exceed a Cmax of 24,500 ng/mL or an AUC0–24 of 161,000 hr·ng/mL, corresponding to the NOAEL identified in female dogs.
Sponsors
Gilva Therapeutics, INC.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
- Male or female participants, aged more than or equal 18 to less than or equal to 65 years at the time of providing informed consent, who are non-smokers (no use of tobacco or nicotine-containing products within 3 months prior to screening), with a body mass index (BMI) greater than 18.0 and less than 32.0 kilogram/meter square, and a minimum body weight of 50.0 kilogram. - Healthy individuals, as determined by the Principal Investigator or delegate, defined as: a. No clinically significant illness or surgical procedures within 4 weeks prior to study drug administration. b. No clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, or metabolic disorders. - Capable of understanding the study procedures and willing to provide written informed consent prior to participation.
Exclusion criteria
- Any clinically significant abnormal finding on physical examination, as determined by the Principal Investigator or delegate. - Clinically significant abnormal laboratory results at screening, in the opinion of the Principal Investigator or delegate. - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and/or total bilirubin levels greater than 1.5 × the upper limit of normal (ULN) at screening. - Estimated glomerular filtration rate (eGFR) Less than or equal 90 milliliter/minute/1.73 meter square at screening, calculated using the CKD-EPI equation. - Positive test results at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen or antibody. Participants with a positive hepatitis B surface antibody (HBsAb) due to prior vaccination are permitted. - Any current active infection, including localized infections, or a recent history (within 1 week prior to dosing) of infection, cough, or fever, or a history of recurrent or chronic infections. - Any disease or history of surgery that, in the opinion of the Principal Investigator or delegate, could significantly affect the absorption, distribution, metabolism, or excretion of the investigational product. - Positive pregnancy test or lactation in female participants. - Positive urine drug screen, urine cotinine test, or alcohol breath test. - History of clinically significant allergic reactions, including anaphylaxis, hypersensitivity, or angioedema, to any medication, or known allergy to GV-100, related compounds, or any formulation excipients. - Clinically significant abnormalities in ECG findings or vital signs at screening, as determined by the Principal Investigator or delegate. - Supine systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 95 millimeters of mercury. (mmHg) at screening after at least 5 minutes of rest. If elevated, blood pressure will be repeated two additional times, and the average of three measurements will be used to assess eligibility. - History of drug abuse within 6 months prior to first dosing, or substance abuse considered clinically significant by the Principal Investigator or delegate. - History of alcohol abuse within 6 months prior to first dosing, defined as consumption exceeding 21 units per week for males or 14 units per week for females (1 unit = 240 milliliter beer, 120 milliliter wine, or 30 milliliter distilled Alcohol). - Use of depot injections or implants within 3 months prior to first dosing. - Receipt of live or live-attenuated vaccines (bacterial or viral) within 12 weeks prior to screening, or planned receipt during the study period. - Receipt of any vaccine, including COVID-19 vaccines, within 14 days prior to first dosing. - Use of any drug known to induce or inhibit hepatic drug-metabolizing enzymes within 30 days or 5 half-lives (whichever is longer) prior to first dosing. - Use of prescription medications within 14 days or 5 half-lives (whichever is longer) prior to first dosing. - Use of over-the-counter medications or natural health products, including herbal remedies (e.g., St. John’s wort), traditional medicines, probiotics, dietary supplements, or sports supplements within 14 days or 5 half-lives (whichever is longer) prior to first dosing, except for occasional paracetamol up to 2 grams/day. - Participation in another clinical research study involving an investigational or marketed drug or device within 30 days or 5 half-lives (whichever is longer) prior to first dosing; participation involving a biological product within 90 days prior to dosing; or concurrent participation in any investigational study without drug or device administration. - Donation of plasma or platelets within 14 days prior to dosing, or donation or loss of equals 500 milliliter of whole blood within 60 days prior to dosing. - Previous exposure to GV-100. - Any other condition or circumstance that, in the opinion of the Principal Investigator or delegate, could interfere with study participation or compliance, which will be documented in the source records.
Outcome results
None listed