Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PDE9i · 1 trial · 1 indication
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| cohort 1 PF-04447943 | EXPERIMENTAL | - |
| cohort 2 PF-04447943 | EXPERIMENTAL | - |
| placebo comparator | PLACEBO_COMPARATOR | - |
| optional cohort of PF-04447943 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| PDE9i | DRUG | oral dose, every 12 hours for 28 days |
| placebo for PDE9i | DRUG | oral dose, every 12 hours for 28 days |
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 ...
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.
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.
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.
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.
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.
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.