Oral Posaconazole in High Risk Patients With Gastrointest... | NCT00686543

NCT00686543

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
EudraCT No. 2007-003148-31

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15	Experimental	POS 200 mg three times a day (TID) on Days 1-8 followed by continued randomized dosing regimen of POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15	Experimental	POS 200 mg TID on Days 1-8 followed by randomized dosing regimen of POS 400 mg twice a day (BID) on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15	Experimental	POS 200 mg TID on Days 1-8 followed by randomized dosing regimen of POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Posaconazole	Drug	Posaconazole will be used for prophylaxis	POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15 POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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
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
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
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
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
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15

Eligibility Module

Eligibility Criteria

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.

PubMed Identifier	Type	Citation	Retractions
22290953	Result	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 high risk for invasive fungal infection. Antimicrob Agents Chemother. 2012 May;56(5):2652-8. doi: 10.1128/AAC.05937-11. Epub 2012 Jan 30.

Arm/Group Information

ID	Title	Description
FG000	Not Randomized	Posaconazole oral suspension (POS) 200 mg Three Times a Day (TID) on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8)
FG001	POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15	POS 200 mg TID on Days 1-8 Followed by POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to continue with POS 200 mg TID on Days 9-15).
FG002	POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15	POS 200 mg TID on Days 1-8 followed by POS 400 mg Twice a Day (BID) on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg BID on Days 9-15).
FG003	POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15	POS 200 mg TID on Days 1-8 followed by POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to POS 400 mg TID on Days 9-15).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Not Randomized	POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who discontinued anytime before randomization on Day 8).
BG001	POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Analysis of the primary outcome was done on the Balanced Data Set, defined as all participants with no missing pharmacokinetic data for Days 3, 8, and 15 (n=49). From Days 1 to 8, these 49 participants received 200 mg TID. From Days 9 to 15, these 49 participants were randomized to either 200 mg TID (n=19), 400 mg BID (n=14), or 400 mg TID (n=16).

Posted

Mean

90% Confidence Interval

ng/mL

Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8

ID	Title	Description
OG000	POS 200 mg TID Days 1-8	POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements (participants who received POS 200 mg TID on Days 1-8 and were then randomized to one of the three dosing regimens for Days 9-15).

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	POS 200 mg TID on Days 1-8	POS 200 mg TID on Days 1-8, administered with food or oral nutritional supplements.

ID	Term
D009181	Mycoses
D015470	Leukemia, Myeloid, Acute
D009503	Neutropenia

ID	Term
D001423	Bacterial Infections and Mycoses
D007239	Infections
D007951	Leukemia, Myeloid
D007938	Leukemia