Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)

Acute Myelogenous Leukemia Clinical Trial

Official title:

A Phase 4 Study of the Pharmacokinetics of Oral Posaconazole (SCH 56592) Among Patients With Compromised Gastrointestinal Function and at High Risk for Invasive Fungal Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00686543
• Other study ID #: P05115
• Secondary ID: EudraCT No. 2007
• Status: Completed
• Phase: Phase 4
• First received: May 27, 2008
• Last updated: October 8, 2015
• Start date: December 2007
• Est. completion date: April 2009

Study information

• Verified date: October 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is: to explore the potential for different dosing strategies of posaconazole oral suspension (POS) to increase plasma levels and to profile the pharmacokinetics of these dosing strategies in patients with compromised gastrointestinal function and at high risk for Invasive Fungal Infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects >=18 years of age

• High risk of poor enteral medication absorption, based on the effects of cytotoxic chemotherapy, as evidenced by, but not limited to, mucositis, nausea, vomiting, and diarrhea, at baseline.

• High risk of invasive fungal infection (IFI) based on anticipated or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3 [0.5 x 10^9/L]).

• Clinical laboratory safety tests within normal limits or clinically acceptable to the investigator or sponsor.

• Free of any clinically significant disease (other than the primary hematologic disease) that would interfere with the study evaluations.

• Subjects must be willing to give written informed consent and able to adhere to dosing, study visit schedule, and mandatory procedures.

Exclusion Criteria:

• Female subjects who are pregnant, intend to become pregnant, or are nursing.

• Excluded prior treatments. Subjects receiving systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment (ie, voriconazole, fluconazole [FLU], or itraconazole [ITZ]).

• Subjects receiving posaconazole for prophylaxis against IFI 10 days prior to enrollment. (Subjects who are receiving either voriconazole or micafungin for prophylaxis against IFI should discontinue those therapies upon enrollment.)

• Subjects with moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than two times the upper limit of normal (ULN), or a total bilirubin level greater than two times the ULN.

• Subjects who have taken prohibited medications more recently than the indicated washout period prior to Enrollment.

• Subjects who must take prohibited medications during the study.

• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

• Subjects who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry.

• Subjects who are part of the staff personnel directly involved with this study.

• Subjects who are a family member of the investigational study staff.

• Prior enrollment in this study.

• Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents.

• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status >2 prior to induction chemotherapy for their underlying disease.

• Subjects with proven or probable invasive or systemic fungal infection at Baseline.

• Subjects with a history of acute lymphoblastic leukemia or chronic myelogenous leukemia without blast crisis.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Fungal Infection
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Mycoses
• Neutropenia

Intervention

Drug:
• Posaconazole
Posaconazole will be used for prophylaxis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Cornely OA, Helfgott D, Langston A, Heinz W, Vehreschild JJ, Vehreschild MJ, Krishna G, Ma L, Huyck S, McCarthy MC. Pharmacokinetics of different dosing strategies of oral posaconazole in patients with compromised gastrointestinal function and who are at — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean POS Plasma Concentrations on Days 2, 3, and 8.	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8	No
Primary	Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15	No
Primary	Participants With a Mean POS Plasma Concentration =/<250 ng/mL on Day 3 and =/<500 ng/mL on Day 8	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 3 and 8	No
Primary	Participants With a Mean POS Plasma Concentration =/<350 ng/mL on Day 3 and =/<700 ng/mL on Day 8	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 3 and 8	No
Primary	Participants With a Mean POS Plasma Concentration =/<250 ng/mL on Day 8 and =/<500 ng/mL on Day 15	Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15	No
Primary	Participants With a Mean POS Plasma Concentration =/<350 ng/mL on Day 8 and =/<700 ng/mL on Day 15	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15	No