Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase 1b, Randomized, Double-blind (Sponsor Open), Placebo Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf 04447943, Co-administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease

ClinicalTrials.gov ID

NCT02114203

Acronym / sponsor ID

B0401016

Conditions

Phase 1 Sickle Cell

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

30 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

Dec 2014 (actual)

Primary completion

Sep 2016 (actual)

Study completion

Sep 2016 (actual)

First posted

15 Apr 2014 (estimated)

Results

Posted 14 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Basic science

Allocation

Randomised

Masking

Triple blind (participant, care provider, investigator)

Number of arms

4

Who may qualify

Ages

18 to 65 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Vital Signs

   Time frame: 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.

2. Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Neurologic Function

   Time frame: 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.

3. Number of Participants With Potentially Clinically Important (PCI) Change in Physical Examination Findings

   Time frame: 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.

4. Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings

   Time frame: 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.

5. Number of Participants With Potentially Clinically Important (PCI) Change From Baseline in Symptoms of Sickle Cell Disease

   Time frame: 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.

6. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

   Time frame: 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.

7. Number of Participants With Laboratory Test Abnormalities

   Time frame: 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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2017.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 30597771Charnigo 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.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

23 sites in 5 countries: see every site and its status.