Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
Condition: Autosomal Dominant Polycystic Kidney; ADPKD
MeSH terms: Arthrogryposis; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Intervention: Tesevatinib; Placebo
Intervention description: Pharmaceutical form: Tablet; Route of administration: orally; Pharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally
Intervention MeSH terms: XL647
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: ADPKD; Autosomal Dominant Polycystic Kidney Disease; Polycystic Kidney; Tesevatinib; Polycystic Kidney Disease; PKD

Summary:

      The goal of the study was to compare and evaluate safety and efficacy of tesevatinib 50
      milligrams (mg) versus placebo in participants with autosomal dominant polycystic kidney
      disease (ADPKD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  ADPKD diagnosis based on Ravine's criteria.

          -  Cysts of at least 1 centimeter.

          -  Estimated glomerular filtration rate greater than or equal to (>=) 25 milliliter per
             minute per 1.73 square meter (mL/min/1.73 m^2) and less than or equal to (<=) 90
             mL/min/1.73 m^2, using the Modification of Diet in Renal Disease-4 variable formula.

          -  htTKV must meet the following requirements: >= 500 milliliters (mL) for participants
             18-35 years of age; >= 750 mL for participants 36-49 years of age; >= 900 mL for
             participants 50-60 years of age.

          -  The participant had the following laboratory values:

        Platelets greater than (>) lower limit of normal (LLN); Hemoglobin > 9 grams per deciliter;
        Total bilirubin <= 1.5 milligrams per deciliter; Aspartate aminotransferase less than (<)
        2.5*upper limit of normal (ULN); Alanine aminotransferase < 2.5*ULN; Prothrombin
        time/partial thromboplastin time <=1.5*ULN; Serum potassium levels within normal limits;
        Serum magnesium levels within normal limits; Albumin >= LLN; Amylase <=1.5*ULN; Lipase
        <=1.5*ULN; Prothrombin time and partial thromboplastin time <=1.5*ULN; International
        normalized ratio (INR) <=1.5, except those participants taking warfarin who must have INR
        <=3.

          -  Female participants of childbearing potential with negative pregnancy test at
             screening.

          -  If sexually active, the participant agreed to use 2 accepted methods of contraception
             during the course of the study and for 6 months after their last dose of study drug.

        Exclusion Criteria:

          -  Previous nephrectomy.

          -  Kidney transplant.

          -  Tuberous sclerosis.

          -  Hippel-Lindau disease.

          -  Acquired cystic disease.

          -  Congenital absence of 1 kidney and/or need for dialysis or transplantation in the
             foreseeable future.

          -  Moderate hematuria.

          -  Uncontrolled hypertension.

          -  Presence of renal or hepatic calculi (stones) causing symptoms.

          -  Received any investigational therapy within 30 days prior to initiation of therapy
             (Day 1 visit).

          -  Received tolvaptan 30 days prior to initiation of therapy (Day 1 visit).

          -  Received active treatment for urinary tract infection 4 weeks prior to initiation of
             therapy (Day 1 visit).

          -  History of pancreatitis or known risk of pancreatitis.

          -  The participant met any of the following cardiac criteria:

          -  Mean QTc interval corrected for heart rate using Fridericia's formula (QTcF) of >450
             milliseconds.

          -  History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic
             sinus bradycardia (< 50 beats per minute), heart block (excluding first-degree block,
             being PR interval prolongation only), congenital long QT syndrome or new ST segment
             elevation or depression or new Q wave on electrocardiogram.

          -  Participants with a history of atrial arrhythmias were discussed with the Medical
             Monitor.

          -  Family history of congenital long QT syndrome or unexplained cardiac death.

          -  Symptomatic heart failure (per New York Heart Association guidelines), unstable
             angina, myocardial infarction, or cerebrovascular accident within 6 months prior to
             study entry.

          -  History of ventricular rhythm disturbances.

          -  History of cardiac arrhythmias, stroke, or myocardial infarction.

          -  Has a cardiac pacemaker.

          -  History of pericardial effusion or presence of pericardial effusion on screening
             echocardiogram.

          -  Taking any medication known to inhibit the cytochrome P450 (CYP)3A4 isozyme or any
             drugs that are CYP3A4 inducers, or any drugs associated with torsade de pointes or
             known to prolong the QTcF interval, including anti-arrhythmic medications within 2
             weeks prior to screening.

          -  Uncontrolled intercurrent illness that would limit compliance with study requirements.

          -  Participant was pregnant, planed to become pregnant, or nursing.

          -  Human immunodeficiency virus positive.

          -  Hepatitis B or C positive.

          -  Immunocompromised.

          -  Documented renal vascular disease resulting in uncontrolled hypertension.

          -  Previously received an epithelial growth factor receptor (EGFR).

          -  Allergy or hypersensitivity to components of tesevatinib or placebo or their
             formulations.

          -  Been aphakic due to previous cataract surgery or congenital abnormality.