A clinical trial to look at how safe and how effective Lixivaptan in patients with kidney disease compared to a placebo treatment.
- Conditions
- Autosomal Dominant Polycystic Kidney DiseaseMedDRA version: 20.0Level: LLTClassification code 10036046Term: Polycystic kidney, autosomal dominantSystem Organ Class: 100000004850Therapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2021-003062-12-IT
- Lead Sponsor
- Palladio Biosciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1200
1.Male or female, between 18 and 60 years of age (inclusive) at the time of Screening (Visit 1a).
2.Diagnosis of ADPKD by modified Pei criteria:
•For participants with family history of ADPKD, by ultrasound:
- 18-39 years: =3 cysts, unilateral or bilateral;
- 40-59 years: =2 cysts in each kidney;
- 60 years: =4 cysts in each kidney; or
•For participants with family history of ADPKD, by computerized tomography (CT) or MRI:
- 18-40 years: =10 cysts in both kidneys; or
•For participants without family history of ADPKD
- a minimum of 10 cysts per kidney by any radiologic method and
exclusion of other cystic kidney diseases (multiple simple kidney
cysts, renal tubular acidosis, cystic dysplasia of the kidney,
multicystic kidney, multilocular cysts of the kidney, medullary
cystic kidney and acquired cystic disease of the kidney); or
- genetic diagnosis of ADPKD.
3.Mayo Clinic ADPKD classification of 1C, 1D, or 1E based on age and height-adjusted total kidney volume as determined by kidney MRI obtained during Screening, as assessed by the central imaging vendor.
4.eGFR =25 mL/min/1.73 m2 and =90 mL/min/1.73 m2 based on the mean of 2 eGFR determinations (Visits 1a and 2 or Visits 1b and 2, if Visit 1b is required) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation
from serum creatinine values obtained during Screening (Appendix 1 (Section 13.1)) Note: This criterion will preliminarily be reviewed at Visit 2 based on Visit 1a or Visit 1b results (if Visit 1b is required). The criterion must be re-evaluated no later than Visit 3 when results for Visits 1a and 2 or Visits 1b and 2 are available.
5.Appropriate control of hypertension including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (unless not considered appropriate for the participant) as suggested by the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease,” without the use of a diuretic.
6.Body mass index (BMI) between 18 and 40 kg/m2 (inclusive) at the time of Screening.
7.Female participants must:
a. not be pregnant, lactating, or breastfeeding.
b. be either postmenopausal (defined as amenorrhea for = 12 months), surgically sterile (defined as having undergone hysterectomy and/or bilateral oophorectomy) or, if of child-bearing potential (WOCBP), agree to practice acceptable methods of birth control or remain abstinent (only if this is the usual and preferred lifestyle of the participant) during the full duration of the trial and for 30 days after the last dose of study drug. Birth control methods that can be used during the study include the following:
•hormonal contraception associated with inhibition of ovulation (i.e., oral, intravaginal, transdermal) progestogen-only hormonal contraception (i.e., oral, injectable, implantable)
•intrauterine device (IUD), including progestin-containing intrauterine devices
•intrauterine hormone-releasing system (IUS)
•male sexual partner who has been vasectomized for at least 3 months prior to Screening and who has obtained a follow-up negative sperm count and is the sole sexual partner
•bilateral tubal ligation
•Essure® procedure (tubal occlusion)
•male or female condom with spermicide (cream, spray, gel, suppository, or polymer film)
•diaphragm, cervical cap, or contraceptive sponge with spermicide (with or without male condom)
8.Ma
1.Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant kidney disease, kidney cancer, transplanted kidney, single kidney, kidney surgery within the past 6 months (including cyst drainage or fenestration) or acute kidney injury within 6 months prior to Screening.
2.Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia).
3.New York Heart Association Functional Class 3 or 4 heart failure or other significant cardiac or electrocardiogram (ECG) findings that could pose a safety risk to the participant.
4.History of infection with HIV unless the participant is stable and doing well on a non-CYP interacting ART regimen and the participant has not required more than 2 changes in their ART regimen since treatment inception.
5.History of clinically significant drug or alcohol abuse in the 2 years prior to Screening Visit 1a.
6.Contraindications to or interference with MRI assessments (e.g., ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, or large abdominal/back tattoos). Investigator should seek MRI safety guidance from the local MRI facility.
7.Any malignancy within 5 years prior to Screening except for basal cell carcinoma successfully treated with local therapy or malignancies that are considered by the Investigator not to affect participant survival (after discussion with the medical monitor).
8.Medical history or findings that preclude safe participation in the trial or participants who are likely to be non-compliant with trial procedures in the opinion of the Investigator or medical monitor.
9.Clinically significant liver disease or impairment or ALT, AST, or total bilirubin values >1.2 x ULN during Screening. Note: This criterion will preliminarily be reviewed at Visit 2 based on Visit 1a and Visit 1b results (if Visit 1b is required). The criterion must be re-evaluated no later than Visit 3 when results for Visit 2 are available.
10.Requirement for ongoing diuretic use.
11.Participants who are currently taking, or are expected to be taking, strong or moderate CYP3A4 or CYP2C8 inhibitors or inducers including regular use of grapefruit juice, Seville oranges, or St. John’s wort. If applicable, there should be a 14-day washout of these treatments prior to Visit 2.
12.Prior use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, empagliflozin, etc.) within the 2 months prior to Screening Visit 1a or expected need for initiation of treatment with a SGLT2 inhibitor during the study.
13.Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor within the 2 months prior to Screening Visit 1a or expected need for initiation of treatment with a HIF-PH inhibitor during the study.
14.Simvastatin at a total daily dose >10 mg or amlodipine at a total daily dose >5 mg.
15.Prior use of tolvaptan or lixivaptan within the 2 months prior to Screening Visit 1a.
16.Prior use of conivaptan, somatostatin analogs (e.g., lanreotide, pasireotide, octreotide, etc.), metformin (except for diabetes), nicotinamide, bardoxolone, demeclocycline, or mTOR kinase inhibitors (e.g., everolimus, sirolimus, etc.) within the 2 months prior to Screening Visit 1a.
17.Participants who have taken any investigational drug or used an investigational device within 30 days, or 5 half-lives, whichever is longer, prior to Scr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method