Fungal InfectionPhase 1NCT01075984

Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)

A Phase 1 study testing Posaconazole and Dextrose 5% in water in people with Fungal Infection, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Fungal Infection
What is being tested?: Posaconazole and Dextrose 5% in water
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 279 participants
Where: No sites listed yet
Study dates: 23 Feb 2010to 20 Nov 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult subjects greater than or equal to 18 years of age (weighing greater than 34 kg [75 lb]), of either sex and of any race/ethnicity.
Disease definition for each subject: Anticipated (likely to develop within 3 days to 5 days) or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3 [0.5 x 10^9/L]) at Baseline and likely to last for at least 7 days due to:
a. Standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent), for a new diagnosis of acute myelogenous leukemia (AML);
b. Chemotherapy for AML in first relapse; or
c. Therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
Disease definition for each Cohort 3 subject: In addition to subjects defined above, allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in either the pre-engraftment period (i.e., after they have received their conditioning regimen for the transplant, but while they are still neutropenic) or in the post-engraftment period if they are receiving immunosuppressive therapy for prevention or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin, mycophenolate mofetil, and antithymocyte globulin).

Who cannot join

A female subject must not be pregnant, must not intend to become pregnant during the study, or must not be nursing.
Excluded prior treatments. A subject must not have received systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment.
A subject must not have moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN. For Cohorts 1 and 2, a subject must not have a known or suspected history of Gilbert's disease.
A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc greater than 500 msec.
A subject must not have prior enrollment in this study, or other POS studies within 90 days of study entry.
A subject must not have a known or suspected invasive or systemic fungal infection at Baseline. Those subjects receiving empiric anti-fungal therapy within 7 days prior to Baseline must have had a diagnostic work-up that ruled out a possible invasive fungal infection.
A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min.
A subject must not have a history of Type I hypersensitivity or idiosyncratic reactions to azole agents.

About this study

Official title: Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05520)

The purpose of this study is to collect pharmacokinetic (PK) information related to how well intravenous Posaconazole (POS IV), is distributed in the body and to determine the safety and tolerability of this new formulation. In addition, the PK, safety, and tolerability of switching from taking POS IV to taking Posaconazole Oral Suspension (POS Oral) will be evaluated. The data collected in this study will be compared to data collected in previous studies.

Individuals who have been diagnosed by their physicians with a blood disease or cancer that can affect their infection-fighting white blood cells will be asked to participate in the trial. Since these blood diseases and their treatments can weaken the immune system, they may put these individuals at a high risk for getting a serious fungal infection of their internal organs or blood (invasive fungal infection). As these fungal infections can be hard to detect early and can be life-threatening, many physicians believe that individuals diagnosed with these diseases should receive antifungal therapy to try to lower their risk of getting this type of infection.

Enrollment into this study will take place in several stages (cohorts). The determination of which cohort an individual will be asked to participate in is based on which cohort is open at the site at the time the individual is approached to consider study participation.

Conditions: Fungal Infection
Being tested: Posaconazole, Dextrose 5% in water
Keywords: Antifungal Agents pharmacokinetics, Mycoses prevention and control
Medical subject headings: Mycoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PosaconazoleDrug
Also called SCH 056592
Dextrose 5% in waterDrug
Also called SCH 056592 (2)

Study groups in NCT01075984
Study group	Role	What they receive
POS IV 200 mg single dose (Cohort 0)	Active comparator	POS 200 mg IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) Receives: Drug: Posaconazole
Dextrose 5% in water (Cohort 0)	Placebo comparator	Placebo IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) Receives: Drug: Posaconazole; Drug: Dextrose 5% in water
POS IV 200 mg BID (Cohort 1)	Experimental	POS 200 mg IV infused over 1.5 hours BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) Receives: Drug: Posaconazole
POS IV 300 mg BID (Cohort 2)	Experimental	POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. Receives: Drug: Posaconazole
POS IV 300 mg BID (Cohort 3)	Experimental	POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28, or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. Receives: Drug: Posaconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Single Dose Trough Concentration of IV Posaconazole (Cmin)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Steady State Trough Concentration of IV Posaconazole (Cmin)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Single Dose Maximum Concentration of IV Posaconazole (Cmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Steady State Maximum Concentration of IV Posaconazole (Cmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1)
Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Steady State Average Concentration of IV Posaconazole (Cavg)
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).
Measured: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Steady State Total Body Clearance of IV Posaconazole (CL)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Steady State Trough Concentration of Oral Posaconazole (Cmin)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Steady State Maximum Concentration of Oral Posaconazole (Cmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Steady State Average Concentration of Oral Posaconazole (Cavg)
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).
Measured: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Steady State Apparent Total Body Clearance of Oral Posaconazole (CL/F)
Blood samples were collected from participants for the determination of plasma POS concentration.
Measured: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Feb 201020 Nov 2012

First posted25 Feb 2010 (estimated)
Study start23 Feb 2010
Primary completion20 Nov 2012
Study completion20 Nov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Fungal InfectionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 279 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01075984
Sponsor's protocol ID: P05520
Status last verified: Oct 2017
First submitted: 24 Feb 2010
Last updated: 13 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Maertens J, Cornely OA, Ullmann AJ, Heinz WJ, Krishna G, Patino H, Caceres M, Kartsonis N, Waskin H, Robertson MN. Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous solution in patients at risk for invasive fungal disease. Antimicrob Agents Chemother. 2014 Jul;58(7):3610-7. doi: 10.1128/AAC.02686-13. Epub 2014 Apr 14.
PubMed 24733463
Cornely OA, Robertson MN, Haider S, Grigg A, Geddes M, Aoun M, Heinz WJ, Raad I, Schanz U, Meyer RG, Hammond SP, Mullane KM, Ostermann H, Ullmann AJ, Zimmerli S, Van Iersel MLPS, Hepler DA, Waskin H, Kartsonis NA, Maertens J. Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. J Antimicrob Chemother. 2017 Dec 1;72(12):3406-3413. doi: 10.1093/jac/dkx263.
PubMed 28961714

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
A Study to Learn About How a New Pneumococcal Vaccine Works in Infants
Pneumococcal Disease
Not yet recruiting
Early Pathophysiology of Hidradenitis Suppurativa and Prediction of the Risk of Progression: a Prospective Cohort
Hidradenitis Suppurativa (HS)
Active, not recruitingPhase 2
Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome Patients
Mycosis Fungoides, Lymphomatoid Papulosis

All Fungal Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05520)
ClinicalTrials.gov ID: NCT01075984
Acronym / sponsor ID: P05520
Conditions: Fungal Infection
Keywords: Antifungal Agents pharmacokinetics, Mycoses prevention and control
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 279 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 23 Feb 2010 (actual)
Primary completion: 20 Nov 2012 (actual)
Study completion: 20 Nov 2012 (actual)
First posted: 25 Feb 2010 (estimated)
Results: Posted 15 Nov 2013

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: Prevention
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
POS IV 200 mg single dose (Cohort 0)	Active comparator	Drug: PosaconazolePOS 200 mg IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
Dextrose 5% in water (Cohort 0)	Placebo comparator	Drug: Posaconazole, Drug: Dextrose 5% in waterPlacebo IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
POS IV 200 mg BID (Cohort 1)	Experimental	Drug: PosaconazolePOS 200 mg IV infused over 1.5 hours BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
POS IV 300 mg BID (Cohort 2)	Experimental	Drug: PosaconazolePOS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
POS IV 300 mg BID (Cohort 3)	Experimental	Drug: PosaconazolePOS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28, or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Adult subjects greater than or equal to 18 years of age (weighing greater than 34 kg [75 lb]), of either sex and of any race/ethnicity.
Disease definition for each subject: Anticipated (likely to develop within 3 days to 5 days) or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3 [0.5 x 10^9/L]) at Baseline and likely to last for at least 7 days due to:
Disease definition for each Cohort 3 subject: In addition to subjects defined above, allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in either the pre-engraftment period (i.e., after they have received their conditioning regimen for the transplant, but while they are still neutropenic) or in the post-engraftment period if they are receiving immunosuppressive therapy for prevention or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin, mycophenolate mofetil, and antithymocyte globulin).

Key exclusion criteria (8 listed)

A female subject must not be pregnant, must not intend to become pregnant during the study, or must not be nursing.
Excluded prior treatments. A subject must not have received systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment.
A subject must not have moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN. For Cohorts 1 and 2, a subject must not have a known or suspected history of Gilbert's disease.
A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc greater than 500 msec.
A subject must not have prior enrollment in this study, or other POS studies within 90 days of study entry.

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

Interventions

Intervention	Type	Arms
PosaconazoleAlso: SCH 056592	Drug	Dextrose 5% in water (Cohort 0), POS IV 200 mg BID (Cohort 1), POS IV 200 mg single dose (Cohort 0), POS IV 300 mg BID (Cohort 2), POS IV 300 mg BID (Cohort 3)
Dextrose 5% in waterAlso: SCH 056592 (2)	Drug	Dextrose 5% in water (Cohort 0)

Primary outcome

Single Dose Trough Concentration of IV Posaconazole (Cmin)
Time frame: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Trough Concentration of IV Posaconazole (Cmin)
Time frame: 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration.
Single Dose Maximum Concentration of IV Posaconazole (Cmax)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Maximum Concentration of IV Posaconazole (Cmax)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration.
Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration.
Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Average Concentration of IV Posaconazole (Cavg)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).
Steady State Total Body Clearance of IV Posaconazole (CL)
Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Trough Concentration of Oral Posaconazole (Cmin)
Time frame: 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Maximum Concentration of Oral Posaconazole (Cmax)
Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax)
Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC)
Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.
Steady State Average Concentration of Oral Posaconazole (Cavg)
Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).
Steady State Apparent Total Body Clearance of Oral Posaconazole (CL/F)
Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)
Blood samples were collected from participants for the determination of plasma POS concentration.

Results and safety

Results posted to the registry on 15 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Posaconazole (POS) 200 mg IV Single Dose (Cohort 0)	10	10
Placebo IV Single Dose (Cohort 0)	11	10
POS 200 mg IV BID (Cohort 1)	21	14
POS 300 mg IV BID (Cohort 2)	24	17
POS 300 mg IV BID (Cohort 3)	213	153

Primary outcome: Single Dose Trough Concentration of IV Posaconazole (Cmin)

Time frame: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2). Mean (Standard Deviation). Unit: ng/mL

Measure	POS 200 mg IV Single Dose (Cohort 0) n = 10	POS 200 mg IV BID (Cohort 1) n = 20	POS 300 mg IV BID (Cohort 2) n = 22
Value	318 (107)	295 (113)	467 (172)

Population analysed: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens. Cohort 3 was not evaluated for this outcome measure.

Primary outcome: Steady State Trough Concentration of IV Posaconazole (Cmin)

Time frame: 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3). Mean (Standard Deviation). Unit: ng/mL

Measure	POS 200 mg IV BID (Cohort 1) n = 15	POS 300 mg IV BID (Cohort 2) n = 19	POS 300 mg IV BID (Cohort 3) n = 30
Value	958 (605)	1046 (515)	1164 (462)

Population analysed: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.

Primary outcome: Single Dose Maximum Concentration of IV Posaconazole (Cmax)

Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2). Mean (Standard Deviation). Unit: ng/mL

Measure	POS 200 mg IV Single Dose (Cohort 0) n = 10	POS 200 mg IV BID (Cohort 1) n = 20	POS 300 mg IV BID (Cohort 2) n = 22
Value	881 (334)	990 (467)	1590 (980)

Primary outcome: Steady State Maximum Concentration of IV Posaconazole (Cmax)

Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3). Mean (Standard Deviation). Unit: ng/mL

Measure	POS 200 mg IV BID (Cohort 1) n = 15	POS 300 mg IV BID (Cohort 2) n = 19	POS 300 mg IV BID (Cohort 3) n = 30
Value	1947 (966)	2610 (1010)	3696 (2950)

Population analysed: The PK-evaluable population included participants who had no major protocol violations and had documented adherence to the dosing and PK regimens.

Adverse events

Time frame: Up to Day 14 (Cohort 0); Up to Day 35 (Cohorts 1, 2, and 3). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
POS 200 mg IV Single Dose (Cohort 0)	2 of 10 (20%)	10 of 10 (100%)	Not reported
Placebo IV Single Dose (Cohort 0)	2 of 11 (18.2%)	11 of 11 (100%)	Not reported
POS 200 mg IV BID (Cohort 1)	4 of 21 (19%)	20 of 21 (95.2%)	Not reported
POS 300 mg IV BID (Cohort 2 and 3)	71 of 237 (30%)	229 of 237 (96.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24733463Maertens J, Cornely OA, Ullmann AJ, Heinz WJ, Krishna G, Patino H, Caceres M, Kartsonis N, Waskin H, Robertson MN. Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous solution in patients at risk for invasive fungal disease. Antimicrob Agents Chemother. 2014 Jul;58(7):3610-7. doi: 10.1128/AAC.02686-13. Epub 2014 Apr 14.
Results publication: PubMed 28961714Cornely OA, Robertson MN, Haider S, Grigg A, Geddes M, Aoun M, Heinz WJ, Raad I, Schanz U, Meyer RG, Hammond SP, Mullane KM, Ostermann H, Ullmann AJ, Zimmerli S, Van Iersel MLPS, Hepler DA, Waskin H, Kartsonis NA, Maertens J. Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. J Antimicrob Chemother. 2017 Dec 1;72(12):3406-3413. doi: 10.1093/jac/dkx263.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

Related trials for Fungal Infection

Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
A Study to Learn About How a New Pneumococcal Vaccine Works in Infants
Pneumococcal Disease
Not yet recruiting
Early Pathophysiology of Hidradenitis Suppurativa and Prediction of the Risk of Progression: a Prospective Cohort
Hidradenitis Suppurativa (HS)
Active, not recruitingPhase 2
Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome Patients
Mycosis Fungoides, Lymphomatoid Papulosis

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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Posaconazole and Dextrose 5% in water in people with Fungal Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Single Dose Trough Concentration of IV Posaconazole (Cmin) (time frame: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01075984, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.