Trial Outcomes & Findings for A Study to Examine the Efficacy and Safety of Posaconazole When Introduced Early in the Treatment of Refractory Fungal Infections (P05090 AM2) (NCT NCT00550732)
NCT ID: NCT00550732
Last Updated: 2017-04-07
Results Overview
Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
Up to 6 months
Results posted on
2017-04-07
Participant Flow
The study was conducted in 8 medical centers across Canada.
Participant milestones
| Measure |
Posaconazole
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
29
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Posaconazole
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Overall Study
Death
|
4
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Palliative care
|
1
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
A Study to Examine the Efficacy and Safety of Posaconazole When Introduced Early in the Treatment of Refractory Fungal Infections (P05090 AM2)
Baseline characteristics by cohort
| Measure |
Posaconazole
n=40 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Age, Customized
|
48 Years
n=99 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: The Efficacy Population included those participants with both a baseline and at least 1 post-baseline assessment.
Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Outcome measures
| Measure |
Posaconazole
n=35 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR) by 12 Weeks or End of Treatment
Complete Response
|
26 Percentage of participants
|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR) by 12 Weeks or End of Treatment
Partial Response
|
46 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: This outcome measure was not reported as the Safety and Steering Committee (SSC) no longer considered it relevant based on revised Mycoses Study Group and European Organization for Research and Treatment of Cancer (MSG/EORTC) Consensus Criteria.
Reduction in lesion size was analyzed by computed tomography (CT) scan. An imaging response was defined as \>=50% reduction in lesion size for pulmonary and cerebral disease or \>=50% reduction in the number of lesions for liver disease.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 WeeksPopulation: The Efficacy Population included those participants with both a baseline and at least 1 post-baseline assessment.
Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Outcome measures
| Measure |
Posaconazole
n=35 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Percentage of Participants With a CR or PR by 12 Weeks
|
75 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 26 weeksPopulation: The Efficacy Population included those participants with both a baseline and at least 1 post-baseline assessment.
Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Outcome measures
| Measure |
Posaconazole
n=35 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks
Week 4, CR
|
6 Percentage of Participants
|
|
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks
Week 26, CR
|
26 Percentage of Participants
|
|
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks
Week 4, PR
|
28 Percentage of Participants
|
|
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks
Week 26, PR
|
48 Percentage of Participants
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: The Efficacy Population included those participants with a visit 6 months after the last dose.
Infection-free survival was the proportion of evaluable participants included in the efficacy analysis who are infection-free and alive at 6 months post last dose visit. Infection-free is defined as the resolution of signs and symptoms of infection.
Outcome measures
| Measure |
Posaconazole
n=25 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Percentage of Participants With Infection-free Survival After the Last Dose of Study Drug
|
56 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: All enrolled participants
Total number of participant survivors was assessed at 3 months.
Outcome measures
| Measure |
Posaconazole
n=40 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Overall Survival at 3 Months
|
85 Percentage of Participants
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: The proportion of participants with response to posaconzole who received a prior combination antifungal regimen is not reported as per recommendation from the Safety and Steering Committee since only 1 participant was evaluable for this outcome measure.
Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: All enrolled participants who received at least one dose of study medication.
An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Outcome measures
| Measure |
Posaconazole
n=40 Participants
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Number of Participants Experiencing Adverse Events (AEs)
|
39 Number of participants
|
Adverse Events
Posaconazole
Serious events: 16 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Posaconazole
n=40 participants at risk
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Cardiac disorders
Cardiomyopathy
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Nausea
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Chills
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Generalised oedema
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Pyrexia
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Bronchopneumonia
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Device related sepsis
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Ludwig angina
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Lung infection pseudomonal
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Pharyngitis
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Pneumonia
|
7.5%
3/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Respiratory tract infection
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Sepsis
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Septic shock
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Streptococcal sepsis
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Investigations
Liver function test abnormal
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Investigations
Oxygen saturation decreased
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Nervous system disorders
Neurotoxicity
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Renal and urinary disorders
Renal failure acute
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary cavitation
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
2.5%
1/40 • Number of events 1 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
Other adverse events
| Measure |
Posaconazole
n=40 participants at risk
Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Cardiac disorders
Tachycardia
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
15.0%
6/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Constipation
|
15.0%
6/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
27.5%
11/40 • Number of events 11 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Nausea
|
32.5%
13/40 • Number of events 15 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Oral pain
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
5/40 • Number of events 6 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Chest pain
|
12.5%
5/40 • Number of events 5 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Disease progression
|
10.0%
4/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Fatigue
|
17.5%
7/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Oedema peripheral
|
10.0%
4/40 • Number of events 5 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Pain
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
General disorders
Pyrexia
|
12.5%
5/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Bacteraemia
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.5%
3/40 • Number of events 6 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.0%
6/40 • Number of events 6 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.0%
6/40 • Number of events 8 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.0%
4/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Nervous system disorders
Dizziness
|
10.0%
4/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Nervous system disorders
Headache
|
20.0%
8/40 • Number of events 8 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
4/40 • Number of events 6 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Psychiatric disorders
Insomnia
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.0%
6/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.5%
7/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
15.0%
6/40 • Number of events 7 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
7.5%
3/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.0%
6/40 • Number of events 6 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Vascular disorders
Hypotension
|
10.0%
4/40 • Number of events 4 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
|
Vascular disorders
Thrombosis
|
7.5%
3/40 • Number of events 3 • Up to 12 months
The Safety Population included all enrolled participants who received at least one dose of study medication.
|
Additional Information
Senior Vice President, Globalo Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Principal Investigators agree to provide review copies of abstracts or manuscripts for publication (including texts of oral presentations) which report any results of the protocol study to the sponsor, 30 days prior to submission for publication or presentation. The sponsor shall have the right to review and comment on the data analysis and presentation with regard to proprietary information and the accuracy of the information contained in the publication.
- Publication restrictions are in place
Restriction type: OTHER