Primary ObjectiveTo determine the safety and tolerability of multipledoses of PF-04447943 Secondary ObjectiveTo characterize the PK of PF-04447943 in plasma following oral administrationExploratory ObjectivesTo evaluate biomarkers that may be…
ID
Source
Brief title
Condition
- Haemoglobinopathies
- Blood and lymphatic system disorders congenital
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety will be assessed through adverse events, changes in laboratory results,
changes in ECG measurements, and changes in vital sign measurements
Secondary outcome
Pharmacokinetic endpoints will include plasma PF-04447943 AUC(0-12h), C12h,
Cmax, and Tmax on Days 1. C1h and C2h will also be measured on Days 7 to assess
steady-state Cmax.
Pharmacodynamic endpoints will include:
Plasma cGMP
Markers associated with cellular adhesion:
E-selectin, P-selectin
ICAM, VCAM
Platelet-monocyte aggregates, platelet neutrophil aggregates
MAC-1 expression on monocytes and neutrophils
Markers associated with coagulation:
Tissue Factor
Thrombin-Antithrombin Complexes
Prothrombin Fragments F1 + F2
D-dimers;
Circulating endothelial microparticles
Hemoglobin F
Background summary
This study is the first evaluation of PF-04447943, a selective inhibitor of the
cyclic guanosine monophosphate (cGMP) specific phosphodiesterase-9A (PDE9A)
enzyme, in subjects with sickle cell disease (SCD). The goal is to assess the
safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in
subjects with stable sickle cell disease with and without co-administration of
hydroxyurea (HU). This study will also aid in
dose selection and evaluation of exploratory biomarkers.
(see page 17)
Study objective
Primary Objective
To determine the safety and tolerability of multipledoses of PF-04447943
Secondary Objective
To characterize the PK of PF-04447943 in plasma following oral administration
Exploratory Objectives
To evaluate biomarkers that may be informative in demonstrating the
pharmacologic effect and to characterize the pharmacodynamics of PF-04447943
Study design
A Randomized, Double-Blind (Sponsor Open), Placebo-Controlled multi center
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and
Pharmacodynamics of PF-04447943 in SCD patients, Co-Administered with and
Without Hydroxyurea.
Intervention
Multiple doses of PF-04447943 or placebo.
Study burden and risks
Burden: PF-04447943/placebo administration, measurements, blood sampling,
compliance with strict lifestyle restrictions and time investment.
Risks: potential side effects of PF-04447943 and potential complaints caused by
being fasted and blood sample collection
Main Street- 5th Floor 610
Cambridge MA 02139
US
Main Street- 5th Floor 610
Cambridge MA 02139
US
Listed location countries
Age
Inclusion criteria
- Stable SCD patients (Hbss or HbSB-thalasamia)
- Male/female, age 18-65, BMI 17.5-35, incl
(see protool p31)
Exclusion criteria
- Recent Vaso occlusive crisis (<2 months)
- Severe infection (<1 month)
- Recent surgery (<3 months)
-Use of CYP3A4 inhibitors/inducers; use of PDE5 inhibitors; use of QT-prolonging medication/medication lowering seizure threshold
-History of cerebrovascular accident or seizure disorder
(see protocol p32)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001677-13-NL |
| CCMO | NL53295.056.15 |
| Other | US IND Number 119,467 |