Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease
NCT ID: NCT02114203
Last Updated: 2017-12-14
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
30 participants
INTERVENTIONAL
2014-12-31
2016-09-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
BASIC_SCIENCE
TRIPLE
Study Groups
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cohort 1 PF-04447943
PDE9i
oral dose, every 12 hours for 28 days
cohort 2 PF-04447943
PDE9i
oral dose, every 12 hours for 28 days
placebo comparator
placebo for PDE9i
oral dose, every 12 hours for 28 days
optional cohort of PF-04447943
PDE9i
oral dose, every 12 hours for 28 days
PDE9i
oral dose, every 12 hours for 28 days
PDE9i
oral dose, every 12 hours for 28 days
Interventions
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PDE9i
oral dose, every 12 hours for 28 days
PDE9i
oral dose, every 12 hours for 28 days
placebo for PDE9i
oral dose, every 12 hours for 28 days
PDE9i
oral dose, every 12 hours for 28 days
Eligibility Criteria
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Inclusion Criteria
* Subjects who are being treated with hydroxyurea must be on a stable dose for at least 8 weeks, with the intent of remaining on the same dose of hydroxyurea throughout the clinical trial including the protocol-specified follow-up period. Subjects who are not treated with hydroxyurea should not plan to begin treatment during the study period.
* Body Mass Index (BMI) of 17.5 to 35 kg/m2; and a total body weight \>40 kg (88 lbs
Exclusion Criteria
* Serious infection (requiring hospitalization or parenteral antibiotics) within 1 month of baseline visit.
* History of cerebrovascular accident or seizure disorder.
* Subjects with a history of clinically significant orthostatic blood pressure (BP) changes or clinically significant orthostatic symptoms.
* Known previous diagnosis of acute hepatitis of any aetiology Hepatitis B or C or Human immunodeficiency virus (HIV) infection.
* History of any malignancy except for subjects who had a basal or squamous cell cancer which has been treated and fully resolved for a minimum of 5 years.
* History or evidence of cardiac disease including: myocardial infarction, cardiac arrhythmia
* Systemic therapy with any of the following medications that are strong or moderate CYP3A4 inhibitors within 7 days or 5 half-lives (whichever is longer) or CYP3A inducers within 28 days prior to the first dose of the trial medication, or during the trial.
* Use of PDE5 inhibitors within 7 days prior to the first dose of the trial medication, or at any time during the trial.
* Creatinine clearance \<30ml/min.
* Hemoglobin level \<6 gm/dL.
* Alanine transaminase (ALT/SGPT) and Aspartate aminotransferase (AST/SGOT) \>2x upper limit of normal, (based on clinic laboratory normal range).
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* A positive urine drug screen for illicit drug.
* History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
* Treatment with an investigational drug within 2 months (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
* 12-lead ECG demonstrating QTc \>450 or a QRS interval \>120 msec msec at Screening.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
* A family history of long QT syndrome and/or ECG abnormalities at screening or randomization, including those listed below:
* Subjects with pre-randomization evidence of QTcF prolongation (defined as \>450 ms) at screening or baseline are not eligible for randomization.
* Predominant heart rhythm other than normal sinus rhythm eg, atrial fibrillation, atrial flutter, supraventricular tachycardia.
* Atrioventricular (AV) block greater than first degree.
* Use of concomitant medications that prolong the QT/QTc interval
* Pregnant females and, breast feeding females and females of childbearing potential; male and female subjects of childbearing potential who are unwilling or unable to use highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 30 days after the last dose of investigational product.
* Subjects who lack the capacity to consent for themselves.
18 Years
65 Years
ALL
No
Sponsors
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Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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University of Illinois Hospital and Health Sciences System
Chicago, Illinois, United States
University of Illinois at Chicago Clinical Research Center
Chicago, Illinois, United States
University of Illinois Hospital and Health Sciences System
Chicago, Illinois, United States
Boston Medical Center E7E
Boston, Massachusetts, United States
Boston Medical Center
Boston, Massachusetts, United States
Boston University Medical Center
Boston, Massachusetts, United States
Interfaith Medical Center
Brooklyn, New York, United States
Interfaith Medical Center
Brooklyn, New York, United States
UNC Hospitals' Investigational Drug Service Pharmacy
Chapel Hill, North Carolina, United States
UNC School of Medicine Clinical and Translational Research Center
Chapel Hill, North Carolina, United States
Investigational Drug Services
Richmond, Virginia, United States
Virginia Commonwealth University
Richmond, Virginia, United States
Pfizer Clinical Research Unit
Brussels, , Belgium
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
Milan, , Italy
A.O.O.R Villa Sofia - V. Cervello
Palermo, , Italy
Centre for Human Drug Research
Leiden, , Netherlands
Royal Liverpool and Broadgreen University Hospital Trust
Liverpool, Merseyside, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, , United Kingdom
King's College Hospital NHS Foundation Trust
London, , United Kingdom
Imperial College Healthcare NHS Trust
London, , United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
Manchester, , United Kingdom
Manchester Royal Infirmary
Manchester, , United Kingdom
Oxford University Hospitals NHS Trust
Oxford, , United Kingdom
Countries
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References
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Charnigo RJ, Beidler D, Rybin D, Pittman DD, Tan B, Howard J, Michelson AD, Frelinger AL , III, Clarke N. PF-04447943, a Phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase Ib Randomized, Placebo-Controlled Study. Clin Transl Sci. 2019 Mar;12(2):180-188. doi: 10.1111/cts.12604. Epub 2018 Dec 31.
Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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2014-001677-13
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
B0401016
Identifier Type: -
Identifier Source: org_study_id