ADPKD (Autosomal Dominant Polycystic Kidney Disease)

Autosomal dominant polycystic kidney disease (ADPKD), the most commonly inherited kidney disease, is characterized by the development of cysts in the kidney that impair function. Of those affected, half will progress to end-stage kidney disease by age 60, requiring dialysis or kidney transplant. To date, no effective and safe therapies exist for this deadly disease. Tolvaptan (Tol), the only FDA-approved drug for treatment of ADPKD, has some benefit in slowing kidney disease progression, but Tol causes frequent urination and thirst and also injures the liver in a small number of patients. The investigators' goal, therefore, is to develop new strategies to treat ADPKD that are safe and tolerable. The development of cysts in ADPKD patients results from two main cellular processes. The first is cell growth with an increase in the number of kidney cells that make up the outer surface of the cyst. The second is an increase in fluid secretion into the cysts that develop. The investigators have shown that an enzyme, AMP-activated protein kinase (AMPK), when activated can inhibit both of those processes. Moreover, genetic mutations that cause ADPKD may alter the energy metabolism of the cell, which in turn inhibits AMPK activity. Bempedoic acid (BA), a medication that is FDA-approved for the treatment of individuals with high cholesterol and has a good safety record, activates AMPK. In addition to activating AMPK, BA inhibits a second enzyme called ATP-citrate lyase (ACLY), which is involved in cholesterol synthesis. ACLY has received growing attention as a novel target for cancer treatment. ACLY inhibition blocks increases of cell numbers by inhibiting the lipid synthesis that is required for creation of new cell membranes. This study will test whether targeting these pathways through treatment with BA will help reverse dysfunctional metabolism in individuals with ADPKD and slow disease progression. The investigators will test this using a phase 2 clinical trial in which 120 individuals with rapidly progressive ADPKD and an estimated glomerular filtration rate of 35 or greater will be treated with either BA or placebo (inactive look-alike pill) for two years. Participants on or off a stable dose of Tol will be included in the study. Participants will be recruited from the U. of Vermont, U. of Maryland, and Tufts University, which have active PKD clinics and are recognized by the PKD Foundation as Centers of Excellence. Through follow-up visits and lab work, the investigators will assess the safety and tolerability of BA in the participants as the primary outcomes. The secondary goals are to assess preliminary efficacy and effects of BA on quality of life in study participants. The growth of cysts results in increased volume or size of the kidneys and liver. Total and cyst volumes of the kidney and liver and visceral abdominal fat content via magnetic resonance imaging (MRI) will be measured to gauge the effectiveness of this drug. The investigators also predict that proteins and small molecules involved in regulating cell energy metabolism, inflammation, and injury, as well as proteins directly involved in AMPK and ACLY function, will be altered in ADPKD patients. Levels of these proteins and small molecules may then subsequently change with BA therapy. Exploratory, mechanistic goals of this study are to identify prognostic and predictive urinary biomarkers in study participants. Successful completion of this study would have a significant impact on individuals with ADPKD by laying the groundwork for a new treatment strategy as well as by providing a new way to help guide treatment decisions. In summary, the goals of this phase 2 randomized, double-blind, placebo-controlled clinical trial are to test the safety, tolerability and preliminary efficacy of the drug bempedoic acid, FDA-approved to lower cholesterol, when used in ADPKD patients.

The German ADPKD Tolvaptan Treatment Registry is a prospective, observational, multicentric study of patients suffering from ADPKD that are considered for tolvaptan treatment. All ADPKD patients that are evaluated for treatment indication, or that are planned to be treated with tolvaptan, or that are already treated with tolvaptan are eligible. This registry is designed to provide "real-world" data on treatment management of patients with ADPKD.

This is a single-center, non-randomized, open-label, self-controlled, Phase I clinical trial to evaluate the drug-drug interactions (DDI) of JMKX003142 tablets in healthy adult participants. The study consists of five cohorts (Cohorts 1, 2, 3, 4, and 5). A total of 24 participants are planned enrollment in each of Cohorts 1, 2, 3, and 5, while 16 participants are planned for Cohort 4.

The primary objective of this study is to assess the effect of a therapeutic and supratherapeutic oral dose of JMKX003142 on the corrected cardiac QT interval relative to a placebo in healthy participants

A phase 1 healthy volunteer study to assess the excretion and metabolism as well as the absolute bioavailability of oral JMKX003142. The study will be conducted in two parts: Part 1 to assess the mass balance of JMKX003142 using orally administered radiolabelled JMKX003142; part 2 will assess the absolute bioavailability using JMKX003142 and radiolabelled JMKX003142 as intravenous and oral forms

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JMKX003142 in Participants with Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)

The purpose of this study is to generate clinical evidence and assess the feasibility of a shared decision-making (SDM) model for the selection of Tolvaptan in patients with ADPKD.

To evaluate the effects of oral administration rifampicin or itraconazole capsules on the pharmacokinetics of JMKX003142 in healthy subjects.