6-Month Safety And Efficacy Study Of TTP488 In Patients With Type 2 Diabetes And Persistent Albuminuria

Double-Blind, Randomized, Placebo-Controlled, Phase IIa, Multicenter Study In Patients With Type 2 Diabetes And Persistent Albuminuria To Evaluate The Safety And Efficacy Of A Six Month Regimen Of Orally-Administered TTP488

Current research indicates that TTP488 may be a viable agent for the treatment of diabetic nephropathy. The purpose of this study is to determine the safety and efficacy of a six-month regimen of daily orally-administered TTP488 to patients with diabetic nephropathy.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Other: Placebo; Drug: PF-04494700 (TTP488)

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • Pfizer Investigational Site
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 5C8
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V6E 1M7
      • Pfizer Investigational Site
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • Pfizer Investigational Site
    • Courtice, Ontario, Canada, L1E 3C3
      • Pfizer Investigational Site
    • Fort Erie, Ontario, Canada, L2A 1Z3
      • Pfizer Investigational Site
    • Hamilton, Ontario, Canada, L8M 1K7
      • Pfizer Investigational Site
    • Kitchener, Ontario, Canada, N2G 1N9
      • Pfizer Investigational Site
    • Kitchener, Ontario, Canada, N2H 5Z8
      • Pfizer Investigational Site
    • Millon, Ontario, Canada, L9T 0H7
      • Pfizer Investigational Site
    • North Bay, Ontario, Canada, P1B 2H3
      • Pfizer Investigational Site
    • Oakville, Ontario, Canada, L6H 3P1
      • Pfizer Investigational Site
    • Saint Catherines, Ontario, Canada, L2N 7H8
      • Pfizer Investigational Site
    • Scarborough, Ontario, Canada, M1H 3G4
      • Pfizer Investigational Site
    • Smith Falls, Ontario, Canada, K7A 4W8
      • Pfizer Investigational Site
    • Thornhill, Ontario, Canada, L4J 8L7
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M4N-3M5
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M4R 2G4
      • Pfizer Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female outpatients 31 years of age or older.
• Females must no longer be of child-bearing potential, must have a negative serum pregnancy test, and cannot be breast-feeding.
• Non-vasectomized male must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception.
• Diagnosis of probable Type 2 diabetes after the age of 30 and for at least 6 months prior to the screening visit and: not requiring insulin within first year of diagnosis; no history of diabetic ketoacidosis (DKA); body mass index (BMI) of 40 or less at the screening visit
• Presence of persistent albuminuria with a UACR of 6.7 - 203 mg/mmol Must be taking the highest tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and have been maintained on that dose for at least 3 months prior to the Baseline visit
• Blood pressure(BP) must be stable and well controlled by the judgement of the investigator (goal of the control of BP is 130/80 or less). If required, the use of anti-hypertensives in addition to an ACE inhibitor or an ARB is acceptable.
• Patients with a calculated creatinine clearance of greater than or equal to 30 mL/min and without the presence of clinically significant hematuria or red or white cell casts can be included in the study.

Exclusion Criteria:

• Diagnosis of Type 1 diabetes
• Hemoglobin A1c (HbA1c) >10%
• Females cannot be breast-feeding
• Known renal artery stenosis
• Calculated creatinine clearance <30 mL/min or the presence of clinically significant hematuria of red or white cell casts
• Chronic use of NSAIDs or more than 1 g/day of aspirin
• QTc >450 msec for females or >430 msec for males (a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle)
• Known family history of prolonged QT syndrome
• History of symptomatic congestive heart failure within the last 2 years
• History of syncope in the lst 2 years or recurrent hypokalemia, including that caused by diuretics
• Myocardial infarction or signs or symptoms of unstable coronary artery disease with the last year
• Pulmonary disease or evidence of clinically significant pulmonary symptoms.
• Active neoplastic disease. (Excised cutaneous basal cell carcinomas are not excluded). Patients with stable prostate cancer may be included at the discretion of the Medical Monitor.
• Any clinically significant hematologic or coagulation disorder
• Any clinically significant hepatic disease
• Use of excluded medications: drugs known to significantly increase QTc and/or have increased risk of torsades de point, immunosuppressive agents, cancer chemotherapeutic agents, oral corticosteroids other than maintenance doses equivalent to 7.5 mg prednisone per day, and radiotherapy
• Use of an investigational drug within 30 days or within 5 half-lives of the investigational agent, whichever is longer, or use of an investigational medical device within 2 weeks before or after the study
• Any other disease or condition that, in the opinion of the investigator, makes the patient unsuitable to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Active Comparator: PF-04494700 (TTP488)	Drug: PF-04494700 (TTP488); 60 mg/day for 6 days followed by 20 mg/day for 175 days vs placebo, oral medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary endpoint of efficacy will be assessed by comparing the treatment groups based on the change in urinary albumin-creatinine ratio (UACR)	from baseline to end of treatment (Month 6).

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate treatment on estimated GFR and serum creatinine	evaluated for change from baseline to months 3 & 6
To evaluate the effects of TTP488 on other relevant biomarkers	evaluated at months 1, 3 & 6
To evaluate the safety of TTP488	Ongoing
To evaluate the PK profile of oral TTP488.	Ongoing
To evaluate the effect of treatment with TTP488 on UACR	evaluated from baseline to month 3 visit

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: January 20, 2006
• First Submitted That Met QC Criteria: February 2, 2006
• First Posted (Estimate): February 6, 2006

Study Record Updates

• Last Update Posted (Estimate): October 1, 2009
• Last Update Submitted That Met QC Criteria: September 30, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Urination Disorders; Proteinuria; Diabetic Nephropathies; Albuminuria
• Other Study ID Numbers: B0341001; TTP488-202