NCT01716234

A Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children (P03579)

Terminated Phase 1 Results posted Last updated 27 August 2018

What this trial tests

Phase 1 trial testing Posaconazole 12 mg/kg/day BID in Fungal Infections in 142 participants. Terminated before completion.

Timeline

17 April 2008

Primary endpoint
1 April 2015

1 April 2015

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	142
Start date	17 April 2008
Primary completion	1 April 2015
Estimated completion	1 April 2015

Drugs / interventions tested

• Posaconazole 12 mg/kg/day BID — full drug profile →
• Posaconazole 18 mg/kg/day BID — full drug profile →
• Posaconazole 18 mg/kg/day TID — full drug profile →
• Posaconazole 12 mg/kg/day TID — full drug profile →

Conditions studied

• Fungal Infections — all drugs for Fungal Infections →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 3 Months to 17, any sex, with Fungal Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose) Primary · Up to 12 hours after the first dose (BID dose groups) or up to 8 hours after the first dose (TID dose (TID dose groups)

Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 1. The 12-hour sample was not obtained for the TID dose groups. Day 1 pharmacokinetic samples were not collected for participants 3 months to \<2 years of age weighing \<6.5 kg.

Group	Value	95% CI
POS 12 BID 2 to <7 Years	122	± 101
POS 12 BID 7 to <18 Years	107	± 92.5
POS 18 BID 2 to <7 Years	112	± 86.9
POS 18 BID 7 to <18 Years	113	± 100
POS 18 TID 2 to <7 Years	68.4	± 40.4
POS 18 TID 7 to <18 Years	57.9	± 30.2
POS 12 TID 3 Months to <2 Years	68.5	± 0

Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State) Primary · Up to 12 hours after the first dose on Day 7 (BID dose groups) or up to 8 hours after the first dose on Day 7 (TID dose

Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 7 (steady state). The 12-hour sample was not obtained for the TID dose groups. The target Cavg range was 500 to \<2500 ng/mL.

Group	Value	95% CI
POS 12 BID 2 to <7 Years	604	± 779
POS 12 BID 7 to <18 Years	1050	± 789
POS 18 BID 2 to <7 Years	485	± 306
POS 18 BID 7 to <18 Years	1240	± 1400
POS 18 TID 2 to <7 Years	620	± 411
POS 18 TID 7 to <18 Years	1150	± 750
POS 12 TID 3 Months to <2 Years	453	± 0

Number of Participants With an Adverse Event Secondary · Up to Day 58

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

Group	Value	95% CI
POS 12 BID 2 to <7 Years	21
POS 12 BID 7 to <18 Years	21
POS 18 BID 2 to <7 Years	16
POS 18 BID 7 to <18 Years	26
POS 18 TID 2 to <7 Years	13
POS 18 TID 7 to <18 Years	30
POS 12 TID 3 Months to <2 Years	1

Number of Participants With an Adverse Event Leading to Study Drug Discontinuation Secondary · Up to Day 28

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

Group	Value	95% CI
POS 12 BID 2 to <7 Years	7
POS 12 BID 7 to <18 Years	9
POS 18 BID 2 to <7 Years	2
POS 18 BID 7 to <18 Years	9
POS 18 TID 2 to <7 Years	3
POS 18 TID 7 to <18 Years	6
POS 12 TID 3 Months to <2 Years	0

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs: from Day 1 up to Day 39; SAEs: up to Day 58.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

POS 12 BID 2 to <7 Yrs

Serious: 5/22 (23%)

Deaths: —

POS 12 BID 7 to <18 Yrs

Serious: 3/21 (14%)

Deaths: —

POS 18 BID 2 to <7 Yrs

Serious: 1/19 (5%)

Deaths: —

POS 18 BID 7 to <18 Yrs

Serious: 7/28 (25%)

Deaths: —

POS 18 TID 2 to <7 Yrs

Serious: 7/15 (47%)

Deaths: —

POS 18 TID 7 to <18 Yrs

Serious: 11/30 (37%)

Deaths: —

POS 12 TID 3 Months to <2 Yrs

Serious: 1/1 (100%)

Deaths: —

Serious adverse events (36 terms)

Reaction	System	POS 12 BID 2 to <7 Yrs	POS 12 BID 7 to <18 Yrs	POS 18 BID 2 to <7 Yrs	POS 18 BID 7 to <18 Yrs	POS 18 TID 2 to <7 Yrs	POS 18 TID 7 to <18 Yrs	POS 12 TID 3 Months to <2 …
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Hypothermia	General disorders	—	—	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—	—	—
Multi-organ failure	General disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Hepatic haemorrhage	Hepatobiliary disorders	—	—	—	—	—	—	—
Hepatic vein occlusion	Hepatobiliary disorders	—	—	—	—	—	—	—
Hepatobiliary disease	Hepatobiliary disorders	—	—	—	—	—	—	—
Venoocclusive liver disease	Hepatobiliary disorders	—	—	—	—	—	—	—
Anaphylactic reaction	Immune system disorders	—	—	—	—	—	—	—
Catheter site cellulitis	Infections and infestations	—	—	—	—	—	—	—
Pneumonia klebsiella	Infections and infestations	—	—	—	—	—	—	—
Puncture site infection	Infections and infestations	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—
Streptococcal bacteraemia	Infections and infestations	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—
Chemotherapeutic drug level increased	Investigations	—	—	—	—	—	—	—
Electrocardiogram T wave inversion	Investigations	—	—	—	—	—	—	—

Other adverse events (142 terms — click to expand)

Reaction	System	POS 12 BID 2 to <7 Yrs	POS 12 BID 7 to <18 Yrs	POS 18 BID 2 to <7 Yrs	POS 18 BID 7 to <18 Yrs	POS 18 TID 2 to <7 Yrs	POS 18 TID 7 to <18 Yrs	POS 12 TID 3 Months to <2 …
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—	—
Lip dry	Gastrointestinal disorders	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—
Fluid balance positive	Investigations	—	—	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—	—
Coagulopathy	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—	—	—
Dry eye	Eye disorders	—	—	—	—	—	—	—
Eye pruritus	Eye disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Febrile neutropenia, Headache, Anaemia, Neutropenia, Thrombocytopenia, Bradycardia, Nausea, Hypothermia.

Data from ClinicalTrials.gov NCT01716234 adverse events section.

Sponsor's own description

The purpose of this dose-escalation study is to evaluate the pharmacokinetics, safety, and tolerability of oral posaconazole in immunocompromised children with neutropenia or expected neutropenia.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pharmacokinetics and pharmacodynamics of antifungals in children: clinical implications.
   Autmizguine J, Guptill JT, Cohen-Wolkowiez M, Benjamin DK, et al · · 2014 · cited 40× · PMID 24872147 · DOI 10.1007/s40265-014-0227-3
2. A non-randomized trial to assess the safety, tolerability, and pharmacokinetics of posaconazole oral suspension in immunocompromised children with neutropenia.
   Arrieta AC, Sung L, Bradley JS, Zwaan CM, et al · · 2019 · cited 31× · PMID 30913226 · DOI 10.1371/journal.pone.0212837
3. Advances in the treatment of invasive neonatal candidiasis.
   Botero-Calderon L, Benjamin DK, Cohen-Wolkowiez M. · · 2015 · cited 18× · PMID 25842986 · DOI 10.1517/14656566.2015.1031108