Pediatric PK Study (POS IV and PFS)

Phase 1

Conditions: Prophylaxis of invasive fungal infections in immunocompromised pediatric subjects with neutropenia or expected neutropenia.
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2014-002807-10-CZ

Lead Sponsor: Merck Sharp & Dohme Corp.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 84

Inclusion Criteria

1)Be a child or adolescent of either sex and of any race, 2 to 17 years of age at the time of screening.

2)Have a parent/guardian or legally authorized representative who is willing to give written informed consent. Assent will be obtained from minors according to institutional practices. The guardian/subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.

3)Have documented or anticipated neutropenia (ANC < 500/mm3 [0.5 x 109 /L]) expected to last for at least 7 days following start of study treatment in at least one of the following clinical situations:
a.Acute leukemia,
b.Myelodysplasia,
c.Severe aplastic anemia,
d.Recipients of Autologous HSCT,
e.High risk neuroblastoma,
f.Advanced stage non-Hodgkin’s lymphoma (NHL),
g.Recipients of allogeneic HSCT during the pre-engraftment (neutropenic) period
h.Hemophagocytic lymphohistiocytosis

4)Must have a central line (e.g. central venous catheter, peripherally inserted central catheter, etc.) in place or planned to be in place prior to beginning IV study therapy.

5) If the subject is of reproductive potential and is not surgically sterile (or their partner is not surgically sterile), must agree to remain abstinent* or use (or have their partner use) a medically accepted method of birth control starting from the time of consent through 1 month after completion of the study. Acceptable methods of birth control are: intrauterine device (IUD) with spermicide, diaphragm or cervical cap (if acceptable to local standard of care) with spermicide, contraceptive sponge with spermicide, condom with spermicide, and any registered and marketed hormonal contraceptive that contains an estrogen and/or progestational agent, including oral, subcutaneous, intrauterine or intramuscular agents that is used with a barrier method.

Are the trial subjects under 18? yes
Number of subjects for this age range: 84
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

1)Has a proven or probable IFI, as defined by the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus group criteria, at the time of screening.

2)Has received POS (any formulation) within the past 10 days prior to screening.

3)Is receiving prohibited drugs (has not met the required washout periods as listed in Section 5.5.1) at the time of randomization or is expected to receive such prohibited medications during the course of study therapy.

4)Has laboratory results that are outside of normal limits at screening, as follows:
a)Moderate or severe liver dysfunction, as defined as:
•Aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN), OR
•Alanine aminotransferase (ALT) > 5 times the ULN, OR
•Serum total bilirubin >2.5 times the ULN, OR
•AST or ALT > 3 times ULN with total bilirubin > 2 times ULN,

b)Calculated creatinine clearance <30 mL/min. Creatinine clearance will be calculated using the following equation:
Creatinine clearance = k X height (cm)
Serum creatinine (mg/dL)
Where k = 0.55 for male and female children 1-13 years old; k = 0.7 for adolescent males 13-18 years old, k= 0.55 for adolescent females 13-18 years old; (Schwartz equation)

5)Has QTc prolongation (either based on Fridericia or Bazett’s correction) at screening defined as :
a)Symptomatic QTc prolongation >450 msec (males) or >470 msec (females)
OR
b)Any QTc prolongation of >500 msec

6)Is pregnant or intends to become pregnant during the course of the study, or is breastfeeding at screening.

7)Has a history of anaphylaxis attributed to the azole class of antifungal agents.

8)Has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study, evaluations or optimal participation in the study including:
a)Not expected to receive a minimum of 10 days of POS IV solution

9)Has previously participated in this study

10)Has participated in any Phase 1 clinical study for a medication classified as an Investigational New Drug (IND) within 30 days prior to enrollment or is expected to participate in such a study within 60 days following randomization. Participation in non-IND studies is permitted.

11) Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the pharmacokinetics (PK) of POS IV solution and POS Powder for Oral Suspension (PFS) administered to immunocompromised pediatric subjects (ages 2 years to 17 years)with neutropenia or expected neutropenia.;Secondary Objective: To evaluate the safety and tolerability of POS IV solution and POS Powder for Oral Suspension (PFS) administered to immunocompromised pediatric subjects (ages 2 years to 17 years) with neutropenia or expected neutropenia.;Primary end point(s): The primary endpoint will be steady-state Cavg for both POS IV solution and POS PFS. Cavg will be calculated for patients in each age group per dose cohort.;Timepoint(s) of evaluation of this end point: Cavg will be measured at steady state, occurring at approximately Day 7-10 for each formulation.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Safety & tolerability of POS IV solution and POS PFS, as measured by adverse events, physical examinations, vital signs, clinical laboratory test results, and electrocardiogram (ECG) results.;Timepoint(s) of evaluation of this end point: All subjects who receive at least one dose of study drug will be included in the safety analysis (14 days following the end of study therapy).