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PDE9i

Phase 1

Phase 1 Sickle Cell | Small molecule | Hematology |Pfizer, Inc.|Last Updated: Dec 14, 2017

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment30

FDA Designations

No designations recorded

Clinical trial landscape

PDE9i · 1 trial · 1 indication

Phase 1 1
NCT02114203Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell DiseasePhase 1 Sickle Cell
COMPLETED30 Analytics
PHASE1COMPLETED
Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease
Phase 1 Sickle CellUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Vital Signs
Baseline up to 30 days post last dose on Day 29

Number of participants with changes from baseline in vital signs meeting the following criteria is presented: (1) maximum increase from baseline in supine systolic blood pressure (SBP) \>=30 millimeters of mercury (mmHg); (2) maximum increase from baseline in supine diastolic blood pressure (DBP) \>=20 mmHg; (3) maximum decrease from baseline in supine SBP \>=30 mmHg; and (4) maximum decrease from baseline in supine DBP \>=20 mmHg.

Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Neurologic Function
Baseline up to Day 29

Clinical assessment of neurologic functions included cranial nerve function, coordination, deep tendon reflexes, muscle strength, and reflexes (left and right ankles). Clinical importance of neurologic function changes was determined by the investigator.

Number of Participants With Potentially Clinically Important (PCI) Change in Physical Examination Findings
Baseline up to 30 days post last dose on Day 29

Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Clinical importance of physical examination changes was determined by the investigator.

Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings
Baseline up to 30 days post last dose on Day 29

Maximum absolute values and increases from baseline were summarized for PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization), QRS complex (time from Q wave to the end of S wave, corresponding to ventricle depolarization), and QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval \>=300 msec; (2) QRS complex \>=200 msec; (3) QTcF interval: 450 to \<480 msec; (4) QTcF interval: 480 to \<500 msec; (5) QTcF interval \>=500 msec; (6) PR interval percent increase from baseline \>=25/50 percent; (7) QRS complex percent increase from baseline \>=25/50 percent; (8) QTcF interval increase from baseline: 30 to \<60 msec; (9) QTcF interval increase from baseline \>=60 msec.

Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Symptoms of Sickle Cell Disease
Baseline up to 30 days post last dose on Day 29

The following symptoms were assessed: anemia; fatigue; chronic pain; acute pain; infections; fever; swelling hands; swelling feet; abdominal swelling; pale skin; pale nail beds; yellow tint to skin; whites of eyes turned yellow; stroke. Number of participants with changes from baseline deemed potentially clinically important by the investigator is presented.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Day 1 to 30 days post last dose on Day 29

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to follow-up visit (30 days post last dose on Day 29) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.

Number of Participants With Laboratory Test Abnormalities
Baseline up to 30 days post last dose on Day 29

The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, eosinophils, monocytes, basophils, and lymphocytes), chemistry (blood urea nitrogen/urea, serum creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and high sensitivity C-reactive protein), urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, and microscopy), and other tests (follicle stimulating hormone and serum human chorionic gonadotropin, urine drug screening). Abnormality was determined by the investigator.

Secondary Endpoints

Area Under the Curve From Time Zero to 12 Hours Post Dose (AUC(0-12h)) of PF-04447943
Prior to 0 hour, and 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Prior to 0 hour, and 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 1
Time for Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Prior to 0 hour, and 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 1
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
PurposeBASIC_SCIENCE

Treatment Arms

ArmTypeDescription
cohort 1 PF-04447943EXPERIMENTAL -
cohort 2 PF-04447943EXPERIMENTAL -
placebo comparatorPLACEBO_COMPARATOR -
optional cohort of PF-04447943EXPERIMENTAL -

Interventions

NameTypeDescription
PDE9iDRUGoral dose, every 12 hours for 28 days
placebo for PDE9iDRUGoral dose, every 12 hours for 28 days
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites23

Inclusion Criteria: * Male and female subjects with a confirmed diagnosis of sickle cell disease (HbSS or HBS-β0 thalassemia) between the ages of 18 and 65 years, inclusive * Subjects who are being treated with hydroxyurea must be on a stable dose for at least 8 weeks, with the intent of remaining ...

Countries:United StatesBelgiumItalyNetherlandsUnited Kingdom
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Frequently asked questions about PDE9i

What is PDE9i used for in sickle cell disease?

PDE9i is an investigational small molecule being studied for use in stable sickle cell disease. It was evaluated in a Phase 1 clinical trial to assess its safety, tolerability, pharmacokinetics, and pharmacodynamics when co-administered with and without hydroxyurea in adult subjects with stable sickle cell disease.

What does PDE9i target?

PDE9i is a small molecule that targets phosphodiesterase 9, an enzyme involved in cellular signaling pathways. By inhibiting this target, the drug is being investigated for its potential effects in sickle cell disease, though its precise mechanism of action in this condition is still under clinical investigation.

Who makes PDE9i?

PDE9i is being developed by Pfizer, Inc., a biopharmaceutical company listed on the New York Stock Exchange under the ticker symbol PFE. The drug is currently in Phase 1 clinical development for sickle cell disease.

What phase is PDE9i in?

PDE9i is in Phase 1 clinical development for sickle cell disease. It is an investigational drug and has not been approved by regulatory authorities. One Phase 1 clinical trial has been completed, and the drug is no longer in active clinical trials.

What clinical trials is PDE9i in?

PDE9i was studied in one completed Phase 1 clinical trial, identified as NCT02114203. This randomized, double-blind, placebo-controlled study enrolled 30 adult participants with stable sickle cell disease across the United States, Belgium, Italy, Netherlands, and the United Kingdom.

Is PDE9i the same as PF-04447943?

Yes, PDE9i is also known as PF-04447943. In clinical trials, the drug is referred to by this alternative name, which is used in the study records and scientific literature to identify the compound.