HUMAN CLINICAL STUDIES

During the realisation of the project „Medical compositions to prevent and treat tumorous diseases and their manufacturing procedure” which ended at the end of September 2012, introduction of a two-phase clinical trial programme brought a breakthrough. The project itself was conducted at the Drug Research Centre of Balatonfüred in 2011 and 2012.

During the first phase, tolerability tests performed on healthy volunteers, confirmed that even high doses of Culevit powder drink are safe to use and well-tolerable. Based on these excellent results Culevit powder drink was introduced to the market. The recommended daily dosage of the powder drink (1-2 sacs daily=50-100 tablets) significantly exceeds the daily dosage of Culevit tablet (30 tablets). This dosage is recommended for advanced stage cancer patients.

The aim of the second trial was to assess the safety, tolerability and also the effect on quality of life of the high-dose Culevit drink powder, among cancer patients. Results were very favourable: during the 28-days treatment period daily administration of the preparation significantly improved patients’ quality of life. Patients’ hysical, mental, emotional, social functions improved and their fatigue, pain and dyspnoea decreased.

The scientific examinations and trials will be discussed within the confines of a scientific publication, but until this article is published we briefly summarise the results of the two studies, mentioned above.

OPEN EXAMINATION TO ASSESS THE SAFETY AND TOLERABILITY OF CULEVIT DRINK POWDER TESTED ON HEALTHY VOLUNTEERS

Aim of the study:

Assessment of safety and tolerability of Culevit powder drink by collecting scientific data, tested on healthy volunteers in the daily dose of 25.5g.

The trial was conducted based on European Guidelines of Good Clinical Practice (GCP) (ICH/CPMP/135/95) and instructions of Standard Operating Procedures. The trial was initiated after we received the approval of the Ethics Committee of the institute.

The trial was a one-phase, open trial with multiple administrations of the preparation, conducted with participation of 24 healthy male and female volunteers, between the ages of 18 and 45, with body mass indexes between 18 and 35kg/m2. Based on the results of screening examinations met the requirements of selection/exclusion criteria.

Volunteers were hospitalised 14 hours before the first doses were administered and they spent 8 days in hospital. All volunteers consumed altogether 25.5g of Culevit powder drink in 10 evenly distributed doses throughout day.

Safety testing included the following steps: recording the possible adverse events (AE), the changes in physical status (vital signs, blood pressure, pulse), ECG and laboratory tests (biochemistry, haematology and examination of urine).

Adverse events were recorded every day during the hospitalisation. Before and after administration of the investigated preparation, patients were asked (not guided questions) whether they have any complaints. Questions were asked in a way that all patients would understand them. Besides these if the patient had any complaint, it was recorded as an adverse event.

Laboratory tests (biochemistry, haematology and examination of the urine) were done on the first day and on the day of the last visit, blood pressure and pulse were measured (after 5 minutes resting, in a lying position), 12-lead ECG and physical examination were also done.

Statistical methods:

Only safety data were evaluated. Statistical analysis was performed by the following programmes: SAS 9.2 program, Office 2007 Software package, Adobe Acrobat Professional.

Results:

No serious adverse reactions occurred during the trial.

No adverse reactions occurred which would jeopardize the safety of the patients.

During the treatment period no significant changes were observed among the volunteers, blood pressure and pulse of the patients during the ECG examinations remained normal.

Conclusions

The aim of the trial was to assess safety and tolerability of Culevit powder drink by collecting scientific data, involving healthy volunteers, with administration of multiple doses.

In the applied doses Culevit powder drink was proven to be safe and well-tolerable in case of 11 female and 12 male volunteers who participated and finished the trial.

OPEN TRIAL TO ASSESS THE SAFETY, TOLERABILITY AND EFFECT ON QUALITY OF LIFE OF CULEVIT DRINK POWDER, TESTED ON CANCER PATIENTS

In 2011 a scientific clinical trial („Open trial to assess safety and tolerability of Culevit drink powder, tested on healthy volunteers”) determined the fact that application of Culevit powder drink is safe and well-tolerable.

Aim of the study:

An open examination aiming the assessment of safety, tolerability and effect on quality of life of Culevit powder drink by collecting scientific data, tested on cancer patients in the daily dose of 25.5g.

Changes in quality of life were evaluated with the help of Quality of Life (QoL) questionnaire which is part of EORTC QLQ-C30 (3rd version) developed by the EORTC (European Organisation for Research and Treatment of Cancer) Study Group. Evaluation of the questionnaires was performed based on EORTC QLQ-C30 (3rd version) guidelines. Answers given to questions of the questionnaire provide information on health-related- quality of life changes of patients participating in the trial, suffering from different types of cancers. In each individual case data of the QLQ-C30 questionnaire were adjusted to EORTC QLQ-C30 Reference Values – determined by EORTC Quality of Life Group – based on cancer type, stage and gender of the patient.

The trial was conducted based on European Guidelines of Good Clinical Practice (GCP) (ICH/CPMP/135/95) and instructions of Standard Operating Procedures. The trial was initiated after we received the approval of the Ethics Committee of the Drug Research Centre.

The treatment period was a 28-day-long open trial in which Stage I-IV male and female patients suffering from 50 different types of malignant cancers participated. The age range of the patients were 18-65 years, their Body Mass Indexes were 16.0kg/m2 or more, but not higher than 40.0kg/m2. Based on the questionnaire their quality of life scores were below 30, the life expectancy was more than 6 months and based on the screening examination results they meet the selection/exclusion criteria.

The participants of the trial received first dose of the examined Culevit preparation at the examination spot and they continued the trial as outpatients. All patients received 25.5g Culevit powder drink (dissolved in 0.6l water) every day, in 12 evenly distributed doses.

Assessment of safety was performed during the screening, on the 1st, 2nd, 3rd (on Day 28) visit and during the last visit at the end of the trial. Safety testing included the following steps: recording the possible adverse events (AE), the changes in physical status (vital signs, blood pressure, pulse), ECG and laboratory tests (biochemistry, haematology and examination of urine).

In order to determine adverse events they were asked not guided questions to find out whether patients had any complaints. Questions were asked in a way that all patients would understand them. All adverse events – observed during the trial period – were recorded.

The efficacy assessment was done by filling in the EORTC QLQ-C30 QoL quality of life questionnaire, during screening, on Day 1 and during the 3rd visit on Day 28.

Description of the trial:

During the trial scientific data was collected to assess safety, tolerability of Culevit powder drink and how it affects quality of life in Stage I-IV cancer patient patients suffering from different types of malignant tumours.

Study protocol, examined patients:

The treatment period was 28 days long. The trial consisted of a screening, 3 examinations and a trial-ending visit.

Male and female patients with 50 different, Stage I-IV malignant cancers participated in the trial. The age range of the patients were 18-65 years, their Body Mass Indexes were 16.0kg/m2 or more, but not higher than 40.0kg/m2. Quality of life scores of them were below 30 according to the questionnaire, the life expectancy was more than 6 months and based on screening examination results they meet the selection/exclusion criteria. All patients received 25.5g Culevit powder drink (dissolved in 0.6l water) every day, in 12 evenly distributed doses.

ITT (Intended To Treat) population involved every patient who received even 1 dose of the investigated preparation. ITT population consisted of 50 patients.

PP (Per protocol) population involved those 40 patients who received all doses of the preparation and in case of whom there were no protocol violations during the trial.

Statistical methods

During statistical analysis efficacy and safety data were evaluated.

Processing of statistical data was performed with the help of SPSS 19.0.0 and Office 2010 Software package.

Efficacy analysis was based on the answers of EORTC QLQ-C30 QoL questionnaire, descriptive statistics were applied in case of Quality of Life scores, functional and symptoms scale. Hypothesis testing was done to analyse the changes in average values of QoL, followed from the initial scores until scores of the last assessment. As distribution of the data was not normal we used the Wilcoxon Signes Rank test.

Safety testing was performed in ITT population, while efficacy assessment was performed in PP population.

Results:

Efficacy analysis

Processing the EORTC QLQ-C30 questionnaires on which the trial was based on, showed that as a result of Culevit drink powder therapy average health condition of patients increased significantly (p<0.001) between the first and the last (Day 28) visit. Based on the Quality of Life test average scores of patients’ physical (p=0.001), mental (p=0.007), emotional (P<0.001), social (p=0.009) and role (p<0.001) functions increased as well, while mean scores of fatigue (p<0.001), pain (p<0.001), dyspnoea (p=0.019) and diarrhoea (p=0.003) decreased significantly.

Safety analysis

There were no adverse reactions observed which would endanger patient’s safety.

During the treatment period no significant changes were detected in blood pressure and pulse values of patients, or in ECG findings.

No significant clinical changes were observed in values referring to general physical condition or in findings of laboratory tests.

Conclusions:

THE aim of the trial was to collect scientific data to assess the safety, tolerability and effect on the quality of life of the high-dose (25.5g/day) Culevit powder drink, among 50 Stage I-IV cancer patients suffering from different types of malignant tumours.

Based on answers given to questions of the EORTC QLQ-C30 Quality of Life questionnaire used to assess efficacy, daily administration of 25.5g Culevit powder drink significantly (p<0.001) improved the quality of life of those 40 patients who finished the trial. Physical, mental, emotional, social functions of patients improved, while their fatigue, pain, dyspnoea and diarrhoea eased.

Application of Culevit powder drink in daily dose of 25.5g was proven to be safe and well-tolerated in those of patients finishing the trial.