A clinical trial to evaluate whether a potential new drug is an effective and safe way to make damaged kidneys work better in patients with type II diabetes

• Conditions: Chronic kidney disease (CKD), also known as chronic renal disease; MedDRA version: 15.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-021358-20-PL
• Lead Sponsor: Pfizer Inc.235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-04
• Last Update Posted: 23 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

1. Male or female subjects =18 years. Female subjects must be of non-child bearing potential, defined as:
- Postmenopausal (defined as amenorrheic for at least 2 years or amenorrheic for at least 1 year together with an FSH level >40 IU/L) or
- Surgically sterile (defined as having had a hysterectomy and/or bilateral oophorectomy). All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy) will be considered to be of childbearing potential.
2. Clinical diagnosis of type 2 diabetes together with stages 3a, 3b or 4 CKD, based on an eGFR of 25-59 mL/min/1.73m2. 3. A history of persistent, overt albuminuria; defined as a UACR =300 mg/g
(=33.9 mg/mmol) or equivalent UPCR, total protein excretion or dipstick proteinuria, for greater than 3 months. A mean UACR =300 mg/g (=33.9 mg/mmol) determined from 3 consecutive morning
first pass urine samples AND UACR =300 mg/g (=33.9 mg/mmol) in at least 2 out of 3 of these consecutive samples during the screening period. 4. Stable background therapy of an ACE inhibitor or an ARB for at least 3 months before screening and to be maintained for the duration of the study. 5. Resting BP =150/100 mm Hg, with no history of BP >150/100 mm Hg on more than one occasion (when measured by a health care professional) in the previous 3 months.
6. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD. 2. Subjects who are diagnosed with autosomal dominant polycystic kidney disease (ADPCKD), severe peripheral vascular disease (PVD) or obstructive uropathy. 3. Subjects who have had a kidney transplant, or who require renal replacement therapy, or are expected to require such therapy within 6 months. 4. Subjects who have a history of proteinuria >10 g/day (or equivalent UACR or UPCR) or
serum albumin <20 g/L (<308.6 µmol/L). 5. Subjects with poorly controlled diabetes mellitus, defined as HbA1C >9%. 6. Subjects on combination ACE inhibitor/ARB therapy. 7. Subjects on renin inhibitor therapy (aliskiren, Tekturna/Rasilez) or aliskiren-containing
combination therapy (Valturna). 8. Subjects on aldosterone antagonist therapy (spironolactone or eplerenone). 9. Subjects receiving or likely to receive during the study any of the following medications: Other PDE5 inhibitors must be terminated at least 14 days prior to randomization (Visit 2) and must not be taken at any time during the study; Nitrates or nitric oxide donors on either regular or intermittent basis (oral, sublingual, buccal, transdermal, inhalation or aerosols);
a -adrenoceptor blockers; Moderate to strong inhibitors or inducers of cytochrome P450 3A4 eg, itraconazole, erythromycin, ketoconazole, protease inhibitors. 10. Significant allergy or known intolerance to PDE5 inhibitors or any ingredient in the formulations. 11. Increased susceptibility to vasodilators including those with left ventricular outflow
obstruction (eg, hypertrophic obstructive cardiomyopathy). 12. History of recurrent syncope, or evidence of low BP (<90 mm Hg systolic or <40 mm Hg diastolic) or symptomatic postural hypotension. This includes relevant postural symptoms associated with a fall in systolic BP =20 mm Hg or diastolic BP =10 mm Hg on standing. 13. History of congestive heart failure (NYHA class III or IV) or unstable angina, or a history of myocardial infarction, stroke or transient ischemic attack in the previous 6 months. 14. Loss of vision in one eye due to non-arteritic ischemic optic neuropathy (NAION) regardless of whether or not this event was temporally associated with the use of a PDE5
inhibitor. 15. Hereditary degenerative retinal disorders (eg, retinitis pigmentosa). 16. Risk of priapism eg, sickle cell disease, multiple myeloma and myeloproliferative disorders (eg, myeloid leukemia, polycythaemia, thrombocythaemia). 17. Any relevant clinically significant abnormalities on physical examination or laboratory tests, including subjects with moderate liver function tests abnormalities >1.5 times the
upper limit of normal. 18. Subjects with a family history of prolonged QT syndrome, or who themselves have a QTc of >450 msec at screening, or any clinically significant ischemic changes as assessed
by the investigator by supine 12-lead supine ECG at screening (preference is for QT to be corrected using Fridericia’s correction).
19. Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, hematological disease, pulmonary disease,
hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease.
20. Any malignancy not considered cured (except basal cell carcinoma of the skin). A subj

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of PF-00489791 in the reduction of albuminuria in subjects with type 2 diabetes and overt nephropathy.;Secondary Objective: -To evaluate the safety and tolerability of PF-00489791 in subjects with type 2 diabetes and overt nephropathy.<br>- To evaluate the effect of PF-00489791 on serum creatinine, urinary TGFß1, serum CRP and serum cystatin C in subjects with type 2 diabetes and overt nephropathy.<br>- To evaluate the pharmacokinetics of PF-00489791 in subjects with type 2 diabetes and overt nephropathy.;Primary end point(s): Urinary albumin:creatinine ratio (UACR) at Week 12.;Timepoint(s) of evaluation of this end point: Urinary albumin:creatinine ratio (UACR) at Week 12.