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

Last updated on December 7, 2019

FOR MORE INFORMATION
Study Location
University of Illinois Hospital and Health Sciences System
Chicago, Illinois, 60612-5836 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Phase 1 Sickle Cell
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-65 years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- History of a recent major surgery, within 3 months of baseline visit.

- 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

- Hemoglobin level

- 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.

NCT02114203
Pfizer
Completed
Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease

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Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Study Of PF-04447943, Co-Administered With And Without Hydroxyurea, In Subjects With Stable Sickle Cell Disease
Official Title  ICMJE 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
Brief SummaryThis study is being conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an investigational drug, PF-04447943, in subjects with stable sickle cell disease with and without co-administration with hydroxyurea. This study will also aid in selecting the doses for future studies and evaluation of substances in the blood which may help access the effectiveness of the drug.
Detailed DescriptionNot Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Phase 1 Sickle Cell
Intervention  ICMJE
  • Drug: PDE9i
    oral dose, every 12 hours for 28 days
  • Drug: placebo for PDE9i
    oral dose, every 12 hours for 28 days
Study Arms  ICMJE
  • Experimental: cohort 1 PF-04447943
    Intervention: Drug: PDE9i
  • Experimental: cohort 2 PF-04447943
    Intervention: Drug: PDE9i
  • Placebo Comparator: placebo comparator
    Intervention: Drug: placebo for PDE9i
  • Experimental: optional cohort of PF-04447943
    Interventions:
    • Drug: PDE9i
    • Drug: PDE9i
    • Drug: PDE9i
Publications *Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 31, 2016)
30
Original Estimated Enrollment  ICMJE
 (submitted: April 11, 2014)
64
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion DateSeptember 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female subjects with a confirmed diagnosis of sickle cell disease (HbSS or HBS-?0 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 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:

  • History of a recent major surgery, within 3 months of baseline visit.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Italy,   Netherlands,   United Kingdom,   United States
Removed Location CountriesFrance
 
Administrative Information
NCT Number  ICMJE NCT02114203
Other Study ID Numbers  ICMJE B0401016
2014-001677-13 ( EudraCT Number )
Has Data Monitoring CommitteeNo
U.S. FDA-regulated ProductNot Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS AccountPfizer
Verification DateJuly 2017

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

BY PHONE

Pfizer Clinical Trials Contact Center

1-800-718-1021

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Contact

[email protected]

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