Trial Outcomes & Findings for Posaconazole Treatment of Invasive Fungal Infection (IFI) (P05551) (NCT NCT00811642)

Last Updated: 2017-04-07

Results Overview

EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of Invasive Fungal Infection (IFI) attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

63 participants

Primary outcome timeframe

Treatment week 12

Results posted on

2017-04-07

Participant Flow

Participant milestones

Participant milestones
Measure	Posaconazole 400 mg twice a day (BID) oral suspension for 12 weeks
Overall Study STARTED	62
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Posaconazole 400 mg twice a day (BID) oral suspension for 12 weeks
Overall Study Adverse Event	3
Overall Study Protocol Violation	1
Overall Study Death	2
Overall Study Withdrawal by Subject	7
Overall Study Cumulative use of antifungal agent	2

Baseline Characteristics

Posaconazole Treatment of Invasive Fungal Infection (IFI) (P05551)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Posaconazole n=62 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Age, Continuous	40.41 years STANDARD_DEVIATION 14.752 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants
Region of Enrollment China	62 participants n=5 Participants

PRIMARY outcome

Timeframe: Treatment week 12

Population: Pool of participants were from the Full Analysis Set (FAS): included all randomized participants who received at least one dose of study drug and who had valid data of primary efficacy endpoint for at least one follow-up visit after treatment. Did not include the 3 participants from the SS population (n=62) who withdrew from the study.

Outcome measures

Outcome measures
Measure	Posaconazole n=59 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants Who Had Clinical Response at 12 Weeks With Posaconazole Treatment Complete response	6 Participants
Number of Participants Who Had Clinical Response at 12 Weeks With Posaconazole Treatment Partial response	32 Participants
Number of Participants Who Had Clinical Response at 12 Weeks With Posaconazole Treatment Stable	11 Participants
Number of Participants Who Had Clinical Response at 12 Weeks With Posaconazole Treatment Failure	10 Participants

SECONDARY outcome

Timeframe: Treatment week 4

Population: Pool of participants were from the FAS: included all randomized participants who received at least one dose of study drug and who had valid data of primary efficacy endpoint for at least one follow-up visit after treatment. Did not include the 3 participants from the SS population (n=62) who withdrew from the study.

EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.

Outcome measures

Outcome measures
Measure	Posaconazole n=59 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants Who Had Clinical Response at 4 Weeks With Posaconazole Treatment Complete response	2 Particpants Interval 52.88 to 80.9
Number of Participants Who Had Clinical Response at 4 Weeks With Posaconazole Treatment Partial response	39 Particpants
Number of Participants Who Had Clinical Response at 4 Weeks With Posaconazole Treatment Stable disease	11 Particpants
Number of Participants Who Had Clinical Response at 4 Weeks With Posaconazole Treatment Failure	7 Particpants

SECONDARY outcome

Timeframe: Treatment week 8

Outcome measures

Outcome measures
Measure	Posaconazole n=59 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants Who Had Clinical Response at 8 Weeks With Posaconazole Treatment Complete response	3 Participants Interval 46.38 to 75.4
Number of Participants Who Had Clinical Response at 8 Weeks With Posaconazole Treatment Partial response	34 Participants
Number of Participants Who Had Clinical Response at 8 Weeks With Posaconazole Treatment Stable disease	11 Participants
Number of Participants Who Had Clinical Response at 8 Weeks With Posaconazole Treatment Failure	11 Participants

SECONDARY outcome

Timeframe: Treatment week 4

Population: Only FAS participants with positive fungal culture (of suspected site or blood) were evaluated. Last Observation Carried Forward (LOCF) was used for missing data.

EVALUATION OF FUNGAL ERADICATION: Participants' mycological response to therapy was assessed by the following: Eradication: Negative culture or histologically documented absence of infecting fungal pathogen from a primary site previously positive. Presumed Eradication: Resolution of all IFI attributable symptoms, signs and laboratory or radiological abnormalities in which a repeat culture/biopsy was contraindicated. Persistence: Continued isolation of fungal pathogen from a primary site previously positive or cytological documentation of presence of fungal pathogen.

Outcome measures

Outcome measures
Measure	Posaconazole n=17 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants With Pathogenic Fungal Eradication at 4 Weeks With Posaconazole Treatment Eradication	2 Participants Interval 16.75 to 76.6
Number of Participants With Pathogenic Fungal Eradication at 4 Weeks With Posaconazole Treatment Presumed eradication	6 Participants
Number of Participants With Pathogenic Fungal Eradication at 4 Weeks With Posaconazole Treatment Disease persistence	9 Participants

SECONDARY outcome

Timeframe: Treatment week 8

Population: Only FAS participants with positive fungal culture (of suspected site or blood) were evaluated. LOCF was used for missing data.

Outcome measures

Outcome measures
Measure	Posaconazole n=17 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants With Pathogenic Fungal Eradication at 8 Weeks With Posaconazole Treatment Presumable eradication	6 Participants
Number of Participants With Pathogenic Fungal Eradication at 8 Weeks With Posaconazole Treatment Disease persistence	9 Participants
Number of Participants With Pathogenic Fungal Eradication at 8 Weeks With Posaconazole Treatment Eradication	2 Participants Interval 16.75 to 76.6

SECONDARY outcome

Timeframe: Treatment week 12

Population: Only FAS participants with positive fungal culture (of suspected site or blood) were evaluated. LOCF was used for missing data.

Outcome measures

Outcome measures
Measure	Posaconazole n=17 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participants With Pathogenic Fungal Eradication at 12 Weeks With Posaconazole Treatment Eradication	2 Participants Interval 23.38 to 83.2
Number of Participants With Pathogenic Fungal Eradication at 12 Weeks With Posaconazole Treatment Presumable eradication	7 Participants
Number of Participants With Pathogenic Fungal Eradication at 12 Weeks With Posaconazole Treatment Disease persistent	8 Participants

SECONDARY outcome

Timeframe: Follow-up week 14

Total number of participant deaths was assessed at the end of 2 week post-treatment follow-up (14 weeks). The total number of deaths was compared to the number of survivors at baseline.

Outcome measures

Outcome measures
Measure	Posaconazole n=59 Participants 400 mg twice a day (BID) oral suspension for 12 weeks
Number of Participant Survivors at Week 14 of Post-Posaconazole Treatment Follow-up Survival	57 Participants Interval 85.46 to 99.48
Number of Participant Survivors at Week 14 of Post-Posaconazole Treatment Follow-up Death	2 Participants

Adverse Events

POSACONAZOLE

Serious events: 5 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	POSACONAZOLE n=62 participants at risk 400mg oral suspension BID for 12 weeks
Cardiac disorders PERICARDIAL EFFUSION	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders HAEMATEMESIS	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Infections and infestations ANAL ABSCESS	1.6% 1/62 • Number of events 2 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Infections and infestations LUNG INFECTION	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ACUTE LEUKAEMIA	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Nervous system disorders CEREBRAL HAEMORRHAGE	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	1.6% 1/62 • Number of events 1 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.

Other adverse events

Other adverse events
Measure	POSACONAZOLE n=62 participants at risk 400mg oral suspension BID for 12 weeks
Gastrointestinal disorders ABDOMINAL DISCOMFORT	6.5% 4/62 • Number of events 4 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders ABDOMINAL DISTENSION	9.7% 6/62 • Number of events 6 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders CONSTIPATION	8.1% 5/62 • Number of events 5 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders DIARRHOEA	17.7% 11/62 • Number of events 12 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders NAUSEA	14.5% 9/62 • Number of events 11 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Gastrointestinal disorders VOMITING	6.5% 4/62 • Number of events 4 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
General disorders FATIGUE	8.1% 5/62 • Number of events 8 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
General disorders OEDEMA PERIPHERAL	11.3% 7/62 • Number of events 10 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
General disorders PYREXIA	22.6% 14/62 • Number of events 21 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Hepatobiliary disorders HEPATIC FUNCTION ABNORMAL	9.7% 6/62 • Number of events 7 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Infections and infestations LUNG INFECTION	8.1% 5/62 • Number of events 6 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Metabolism and nutrition disorders HYPOKALAEMIA	25.8% 16/62 • Number of events 22 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Nervous system disorders HEADACHE	6.5% 4/62 • Number of events 4 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders COUGH	8.1% 5/62 • Number of events 6 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	6.5% 4/62 • Number of events 4 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.
Skin and subcutaneous tissue disorders RASH	12.9% 8/62 • Number of events 8 63 participants were screened and enrolled; 62 participants started on study drug and comprised the Safety Set (SS). SS population included randomized subjects who received at least one dose of study drug and valid data of safety endpoints was available for at least one follow-up visit after treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigator (PI) agrees not to publish or publicly present any interim results of the Protocol study without the prior written consent of the Sponsor. PI further agrees to provide to the Sponsor thirty (30) days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the Protocol study. The sponsor shall have editorial rights with respect to publications, abstracts, slides, and manuscripts.
Publication restrictions are in place

Restriction type: OTHER