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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01200394




Registration number
NCT01200394
Ethics application status
Date submitted
10/09/2010
Date registered
13/09/2010
Date last updated
12/03/2019

Titles & IDs
Public title
A Phase 2, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of PF-00489791 In Patients With Type 2 Diabetes And Overt Nephropathy
Scientific title
A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ONCE-DAILY ADMINISTRATION OF A PHOSPHODIESTERASE 5 INHIBITOR (PF-00489791) IN ADULTS WITH TYPE 2 DIABETES AND OVERT NEPHROPATHY
Secondary ID [1] 0 0
2010-021358-20
Secondary ID [2] 0 0
A7331011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Nephropathies 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-00489791
Treatment: Drugs - Placebo

Experimental: PF-00489791 -

Placebo comparator: Placebo -


Treatment: Drugs: PF-00489791
Tablet, 20 mg once daily for 12 weeks

Treatment: Drugs: Placebo
Tablet, placebo once daily for 12 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12
Assessment method [1] 0 0
UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units milligram per millimole (mg/mmol). A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of Week 12\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of Week 12\]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.
Timepoint [1] 0 0
Baseline, Week 12 (Day 5, 6, 7)
Secondary outcome [1] 0 0
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16
Assessment method [1] 0 0
UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units mg/mmol. A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of specified Week\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of specified Week\]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.
Timepoint [1] 0 0
Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)
Secondary outcome [2] 0 0
Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16
Assessment method [2] 0 0
UPCR is a ratio between two measured substances in urine: milligram of protein per millimole (mmol) of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of Week 3, 6, 12, 16\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of Week 3, 6, 12, 16\]) were used to determine UPCR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UPCR.
Timepoint [2] 0 0
Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 12 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)
Secondary outcome [3] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16
Assessment method [3] 0 0
The eGFR was calculated using 4 variable formula developed by the modification of diet in renal disease (MDRD) study group. The 4 variables needed to estimate glomerular filtration rate (GFR) using this formula were serum creatinine concentration (sCr), age, sex (for females, eGFR was multiplied by 0.742) and ethnic origin (for African-Caribbean people only, eGFR was multiplied by 1.212). Thus eGFR in milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) = 175\*(sCr/88.4)\^-1.154\*(Age)\^-0.203\*(0.742 if female)\*(1.212 if African-Caribbean). Baseline eGFR was determined predose at Week 0 (Day 1).
Timepoint [3] 0 0
Baseline, Week 3, 6, 12, 16 (follow-up)
Secondary outcome [4] 0 0
Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16
Assessment method [4] 0 0
Systolic blood pressure (SBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. diastolic blood pressure (DBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. Mean blood pressure (MBP) = diastolic blood pressure + (\[systolic blood pressure - diastolic blood pressure\]/3). After a minimum of 5 minutes of rest, supine BP was measured with the participant's arm supported at the level of the heart.
Timepoint [4] 0 0
Week 0, 3, 6, 12, 16 (follow-up)
Secondary outcome [5] 0 0
Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16
Assessment method [5] 0 0
Serum creatinine concentration was used as a marker of renal function. Baseline serum creatinine concentration was determined predose at Week 0 (Day 1).
Timepoint [5] 0 0
Baseline, Week 3, 6, 12, 16 (follow-up)
Secondary outcome [6] 0 0
Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16
Assessment method [6] 0 0
TGF Beta-1 is a major fibrogenic growth factor implicated in the pathogenesis of renal scarring. It is overexpressed in the diabetic kidney where it may promote matrix accumulation. Baseline TGF Beta-1 concentration was determined predose at Week 0 (Day 1).
Timepoint [6] 0 0
Baseline, Week 3, 6, 12, 16 (follow-up)
Secondary outcome [7] 0 0
Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16
Assessment method [7] 0 0
The CRP is an acute phase reactant which is virtually absent from the blood serum of healthy persons but rapidly appears in blood and body fluids in response to injurious stimuli. Baseline hs-CRP was determined predose at Week 0 (Day 1).
Timepoint [7] 0 0
Baseline, Week 12, 16 (follow-up)
Secondary outcome [8] 0 0
Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16
Assessment method [8] 0 0
Cystatin C is produced by all nucleated cells at a constant rate and is freely filtered at the glomerulus. The blood concentration of cystatin C depends almost entirely on the GFR and is not substantially affected by diet, nutritional status or inflammatory disease. Serum cystatin C had been proposed as an endogenous marker of GFR in participant with chronic kidney disease (CKD) than sCr. Baseline serum cystatin C was determined predose at Week 0 (Day 1).
Timepoint [8] 0 0
Baseline, Week 12, 16 (follow-up)
Secondary outcome [9] 0 0
Plasma Concentration Versus Time Summary of PF-00489791
Assessment method [9] 0 0
Timepoint [9] 0 0
Pre-dose at Day 1 of Week 0, 3, 6 and 12; 4 hours post-dose on Day 1 of Week 0, 3 and 6

Eligibility
Key inclusion criteria
* Male or female subjects greater than or equal to 18 years. Female subjects must be of non-child bearing potential.
* 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.
* Evidence of persistent, overt albuminuria; defined as a UACR greater than or equal to 300 mg/g (greater than or equal to 33.9 mg/mmol) for greater than 3 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD.
* Subjects with poorly controlled diabetes mellitus, defined as HbA1C >9%.
* Subjects on combination ACE inhibitor/ARB therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2013
Sample size
Target
Accrual to date
Final
256
Recruitment in Australia
Recruitment state(s)
NSW,NewcastleVIC
Recruitment hospital [1] 0 0
Renal Research Practice - Gosford
Recruitment hospital [2] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [3] 0 0
Department of Nephrology - New Lambton
Recruitment hospital [4] 0 0
Pharmacy Department - New Lambton
Recruitment hospital [5] 0 0
Melbourne Renal Research Group - Reservoir
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2305 - Newcastle
Recruitment postcode(s) [3] 0 0
2305 - New Lambton
Recruitment postcode(s) [4] 0 0
3073 - Reservoir
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Canada
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Saskatchewan
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Denmark
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Aarhus
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Denmark
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Copenhagen Oe
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Denmark
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Gentofte
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Hong Kong
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Hong Kong
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Hong Kong
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Pokfulam
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Hong Kong
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Quarry Bay
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Hong Kong
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Shatin
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India
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Andhra Pradesh
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India
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Gujarat
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India
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Maharashtra
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Malaysia
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Kelantan
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Malaysia
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Perak
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Malaysia
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Pulau Pinang
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Malaysia
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Sabah
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Malaysia
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Selangor
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Mexico
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DF
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Mexico
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Jalisco
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Mexico
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Mexico CITY
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Mexico
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San Luis
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Mexico
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Angeles Del Pedregal Cp.
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Poland
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Bielsko-Biala
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Poland
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Katowice
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Lublin
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Warsaw
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Warszawa
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Poland
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Wroclaw
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Serbia
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Belgrade
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Serbia
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Nis
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Slovakia
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Bratislava
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Slovakia
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Levice
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Slovakia
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Presov
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Slovakia
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Rimavska Sobota
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South Africa
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Gauteng- South Africa
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South Africa
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Gauteng
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South Africa
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Kwazulu Natal
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South Africa
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Bloemfontein
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South Africa
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Cape Town
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South Africa
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Durban
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South Africa
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Houghton, Johannesburg
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South Africa
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Parow
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South Africa
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Pretoria
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Sweden
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Goteborg
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Sweden
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Stockholm
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Sweden
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Uppsala
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United Kingdom
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South Yorkshire
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United Kingdom
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Coventry
Country [78] 0 0
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Edinburgh
Country [79] 0 0
United Kingdom
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London
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01200394