Clinical trial NCT01125644: Efficacy, Safety and Pharmacokinetics of SPK-843 in the Treatment of Pulmonary Mycosis
Official title: Efficacy, Safety and Pharmacokinetics of SPK-843 in the Treatment of Pulmonary Mycosis. Open Label Phase III Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cryptococcosis or Aspergillosis Infections
Keywords: necrotic pulmonary infections
Lead sponsor: Proaparts srl
Sponsor class: INDUSTRY
First posted: 2010-05-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Recruitment of at least 10 adult patients (men and women) among individuals affected and admitted to the hospitals identified for the clinical study. All patients shall be between 18 and 75 years of age, with confirmed diagnosis of cryptococcosis or aspergillosis . During therapy (14 days) and examination (28 days), the patients will be subject to 7 doctor's visits (day 1,3,7,10,14,21, and 28).

Detailed description: Objective: primary objective Evaluation of the overall global clinical response based on secondary end points from 1 to 6 at the end of the therapy (Study day 14) and at the final visit at the end of the study - follow-up- (Study day 28) in comparison to the initial clinical state.

The evaluation will be based on: improvement/normalization in relation to the semi-quantitative scales at 3, 4 and 5 items or at opinion expressed as positive for at least 3 of the first 6 secondary end points.

secondary objectives

1. Improvement on the basis of clinical symptoms;
2. Antifungal efficacy from the cultures;
3. Improvement on the basis of mycological blood testing;
4. Improvement on the basis of laboratory diagnosis (hemogasanalysis, ESR, CPR);
5. Improvement on the basis of radiological imaging (Rx, CAT HR,...);
6. Improvement on the basis of endoscopic examination;
7. Evaluate the plasma levels of SPK-843 after single dose and after multiple doses;
8. Evaluate the safety in the administration of SPK-843.

Methodology: Open label multi center study

Eligibility criteria: Inclusion Criteria:The following will be included in the study:

* Patients with proven fungal etiology confirmed by mycological culture test and by hystopathological exam ("patients with definite diagnosis"), or patients with fungal infection of which is difficult to determine the etiological agent but with diagnosis of deep mycosis based on blood testing for fungal infection and/or clinical radiological examination, and/or endoscopic clinical examination, clinical symptomatology ("patients with clinical diagnosis").
* Patients being treated with other anti-fungal drugs (i) showing a poor response to the treatment at least after 5 days of administration of the anti-fungal drug, (ii) that have had an adverse reaction to the drug prejudicing its use, determining the risk/benefit ratio unfavorable to the patient.
* Patients between 18 and 75 years of age.
* Patients able to understand the content of the Informed Consent and willing to participate in the study.
* Male and female patients.
* Patients initially admitted to the hospitals identified for this clinical study.
* Informed Consent.

Exclusion Criteria:

* Patients being treated with other anti-fungal drugs with improving clinical symptoms or with an unclear clinical course.
* Patients with intra-venous catheter and hospitalized with a diagnosis of fungemia but without clinical symptomatology twelve hours after the removal of the catheter.
* Patients with serious deep mycosis with low change of clinical efficacy (with a high probability of death event), or with serious concomitant illnesses or with complications, which may make difficult a safety evaluation of the treatment object of this study.
* Patients with a history of allergy to drugs like AMPH-B or with serious allergic reactions to drugs (shock after administration of drugs different from antifungals).
* Patients with serious hepatic, and/or renal, and/or cardiac failure or basic lung disease or with functionality of the organs with the following criteria:

  * AST (GOT) or ALT (GPT) higher five (5) times the highest normal value or 200 UI/L;
  * Blood creatinine higher than 2,0 mg/dl;
  * Proteinuira (qualitative test) 3+ or greater, or a total urinary excretion of proteins (quantitative test) of 3,5 g/day or higher;
  * Hyperkalemia or hypokalemia or with a basic level of sodium of 6,0 mEq/L or greater or less than 2,5 mEq/L;
  * Hyperlipidemia with a basic value of total cholesterol greater than 1,5 times the highest normal values or 300 mg/dl, triglycerides higher than twice the highest normal values or 300 mg/dl;
  * Patients that require the infusion of leucocytes;
  * Patients with arterial thrombosis or with serious coagulative dysfunctions;
  * Patients with diabetes mellitus associated with ketosis ;
  * Pregnant women or women who intend to become pregnant, women in purperium, or breast feeding;
  * Patients that participated in a clinical study (with any type of drugs, including anti-cancer drugs) or that have been recruited for observational clinical studies with pharmaceutical agents a month before the beginning of the treatment with SPK-843;
  * Patients who, according to the doctor, are not considered fit to be recruited in the study.

Primary outcomes:
measure: Evaluation of the overall global clinical response
timeFrame: 28 days
Secondary outcomes:
measure: Evaluate the safety in the administration of SPK-843.
timeFrame: 28 days
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Ospedale Maggiore di Milano IRCCS Policlinico Dipartimento Malattie Cardiovascolari e Respiratorie
Study officials:
affiliation: Ospedale Maggiore di Milano IRCCS Policlinico
name: Luigi Allegra, Ph.D.
role: STUDY_DIRECTOR
affiliation: Ospedale Maggiore di Milano IRCCS Policlinico
name: Francesco Blasi, MD
role: PRINCIPAL_INVESTIGATOR
References: