Full-Service Clinical Trials in Central and Eastern Europe

At the end of April 2012, OCT clinical team prepared documents required for regulatory and ethics submission for a Phase Ib/IIa multinational, randomized, open-label clinical trial of daily administration of the investigational drug versus standard of treatment in  patients with HBeAg negative chronic hepatitis B virus infection.

The following list of documents has been submitted to the Russian Ministry of Healthcare and Social Development by OCT in order to obtain clinical trial approval:  the letter of application; the application form; the power of attorney; the final study protocol; the informed consent form and patient’s information sheet; the insurance agreement for 36 patients; information regarding any compensation for patients; the investigator’s brochure; the list of trial sites; PIs’ CVs and statements of compliance with the study protocol signed by investigators; the document confirming state fee payment; information letter confirming relations between Russian biotech (licensee) and German licenser (developer) and cGMP contract manufacturer.

This study is designed to investigate changes in HBsAg level affected by IND treatment; to assess safety and tolerability, the virological response (HBV DNA level), the biochemical response, PK profile and immunogenicity of the investigational drug.

There will be a 12-week treatment period and a 12-week follow-up period. On receiving the results on viral load and evaluating clinical and biochemical picture of the disease, all the patients will continue their treatment in accordance with the applicable standards.

The study drug has been tested previously in pre-clinical research (mice, rats, dogs, chimpanzee) and a phase I trial in 24 healthy volunteers in the EU. Study drug efficacy in reducing activity of Hepatitis B viral, no cytotoxicity and no lethal outcomes have been demonstrated within early stage research.

The clinical study will be placed in Russia and Ukraine and enroll 32 subjects at 8 sites. Recruitment is to be initiated in August 2012 and ended in December 2012; the clinical trial closure is planned in December 2013. OCT will perform full-service clinical trial support and hope to continue its strategic collaboration with the Sponsor within other clinical research projects.

OCT performed a local investigators’ meeting for a pediatric study in Russia. This is a second Investigator’s meeting for this international randomized Phase III pediatric clinical trial of a new treatment in infants with colitis.
This exciting meeting brought together up to 20 participants from Russian sites.  This is a follow up meeting which aimed at providing status update of the study to the Sponsor and the study sites. OCT was responsible for

• Presentation preparation
• Venue search
• Event Management
• Technical support
• Translation
• Design and Print of hand out materials
• Travel organization

Russian sites already enrolled more than 25 patients into the study. The study is placed is Russia, Poland, USA, Germany and Sweden.  Russian sites are enrolling patients much quicker than other sites around the world. Russian sites are considered top enrollers in this study.  The client is very pleased with current enrollment status at the Russian sites. OCT was contracted by the client to provide rescue study services in 2011. The enrollment was ongoing since 2010, since then only 2 patients were enrolled by the other CRO.

Infant colic is a functional gastrointestinal disorders which affects up to the 30% of the infant population; it is primarily characterized by excessive inconsolable crying starting without any apparent cause and lasting for several hours per day.

Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs) are largely unsatisfactory.

This phase IIa study is designed to evaluate the efficacy of new pediatric oral solution given once daily at two doses in comparison to placebo.

OCT is very experienced in pediatric studies in Russia, Ukraine, Belarus, Baltic States (Latvia, Lithuania and Estonia) and Bulgaria. OCT is your reliable CRO partner.
Please contact us at info@oct-clinicaltrials.com, if you are interested in OCT pediatric experience.

OCT will be attending DIA Annual Meeting in Philadelphia on June 24-28, 2012. If you are looking for a CRO partner to conduct clinical trials in Russia, Ukraine, Bulgaria, Belarus, Latvia, Lithuania, Estonia, Poland and Czech Republic we would be glad to discuss our potential collaboration with you. To set up a meeting, please contact us. OCT will be represented at 2012 BIO International Convention by:

Anna Davydova,
Business Development Associate

OCT will be attending 2012 BIO International Convention in Boston on June 18-21, 2012. If you are looking for a CRO partner to conduct clinical trials in Russia, Ukraine, Bulgaria, Belarus, Latvia, Lithuania, Estonia, Poland and Czech Republic we would be glad to discuss our potential collaboration with you. To set up a meeting, please contact us. OCT will be represented at 2012 BIO International Convention by:
Julia Sardaryan,
Head Business Development,

Natalia Salamova,
Business Development Manager,

OCT will be attending 17th Congress of European Hematology Association in Amsterdam. To set up a meeting, please contact us. We would be glad to see you in Amsterdam.

OCT will be represented at 17th Congress of European Hematology Association by:

Roman Dyatlov,
Project manager,

and Irina Petrova,

Director, Clinical Operations

The ASCO Annual Meeting brings together more than 25,000 oncology professionals from a broad range of specialities. OCT will be represented at 12-th Annual ASCO Meeting by:

Olga Sokolskaya,
Project Manager, Oncology trials

OCT will provide data management and statistics services for a small German biotech company. A full-service OCT data management includes the following:

• CRF Design for Clinical study
• Database Design and Programming
• Site team, CRAs and Sponsor/Project team DM trainings
• Real-Time Data Entry
• Data Cleaning
• Data Coding (using MedDRA, Version 15, and WHO DRUG ATC/DDD Dictionaries)
• SAE/AE Reconciliation
• SAS Programming and Validation
• Statistical Reports

ОСТ Data Management Process in Clinical Study

OCT will start with electronic data management system and CRF template development followed by data management trainings for all PIs and study team. Statistical analyses plan will be prepared by OCT data managers to describe in every detail the statistical methodology of planned analyses, of assumptions made in the analyses, and of planned data transformations. The SAP also documents how missing data will be handled, and contains shells for all of data listings, tables and figures.

Web-based data management process will be applied in this advanced melanoma study in 21 patients. All data will be entered directly from study sites into electronic CRFs (eCRFs). Error checking during data entry at the sites will allow early detection and correction of errors including direct checking against source documents.

OCT data managers will perform interim statistical analysis prior to database lock. The statistical Data gathered after a clinical study requires a precise analysis. OCT statistical analyses are performed using industry standard SAS software. After completion of the analysis, our statistician will write a detailed statistical report describing the statistical methods used and a statistical interpretation of the results. Statistical reports display comparisons between treatment groups for specific outcomes and usually consist of summary statistics for each treatment group and assessment of statistical significance.

OCT offers comprehensive clinical data management services on customer friendly business models. Our clients can be assured that study data is being managed properly. Both internal and external audits of our database have verified low error rates. It does not matter if your clinical study requires paper, or web-based data collection, we have the experience, expertise, and tools to manage your data.

OCT has given an interview dedicated to the topic of clinical trials conduct in Central and Eastern Europe. The discussion covers several issues and touches upon social and healthcare, scientific, as well as some financial aspects.

The discussion started with the overview of the overall picture, including the range of companies, which come to the CEE region.

"Most of our clients and sponsors are companies coming from either WE or the USA but we also can observe a constant increase in the number of Russian and CIS sponsors. I would not say that there are a lot of sponsors exactly from the countries, where we operate, which include mainly Russia, Ukraine, Belarus, Latvia, Lithuania, Estonia and Bulgaria . To a high degree, our customers are from western countries (Germany, Switzerland, the UK, Italy, etc. and also the USA)." (.) An ever-increasing number of Russian companies may to a certain extent be also explained by the favorable legislative conditions. There has been a boom in the Russian pharma industry. There are a lot of start-up biotech pharmaceutical companies, which produce original as well as generic drugs. Naturally, before entering the market, these drugs have to be tested and their safety and effectiveness analyzed, the process being strictly controlled by the competent regulatory authorities (the Ministry of Health and Social Development of the Russian Federation). To encompass all the needed activities, companies address OCT to assist them in this essential matter

The interview touched upon the issue of certain key advantages of the CEE market, which is one of the most widely discussed at the moment. "Among the financial ones we could name the following" - says Ms. Salamova - the overall costs. We could say that the overall cost for conducting clinical trials in Russia, Ukraine and Belarus would be less as compared to those in the USA or WE (however, surely depending on a therapeutic area and the scope and design of the study). What factors stipulate this?

For instance, principle investigator's grants are usually lower than those in the USA and WE, and this is also connected with the fact that, generally speaking, this way physicians can gain additional source of payment. Yet, naturally, this is not the prime reason. Important is also that the investigators participating in clinical trials have an access to new therapies, latest, up-to-date drugs. At the same time, patients are eager to participate in clinical trials because of the access to these new drugs. It is also connected with the fact that there are a lot of patients in this region that have not yet been exposed to new drugs. This enables researchers to include patients into the trials.

Another thing is the timelines, which influence the general price as well as the pace of the trial. This is also one of the key strategic factors for sponsors. Timelines for RA approval and patients` enrollment (which sometimes turns into a crucial point) are quite favourable in this region.

The choice of analyzing laboratories, warehouses and other vendors is pretty extensive. The pharmaceutical industry has been booming in these countries during the last 5-10 years, which imposed other service providers to deal their businesses. It constantly gives us more and more options. Even speaking about the number of clinical trials compared to those from the last year it has grown, especially in case of phase 3 and 4 trials," - clarifies Ms. Salamova.

The question of the current existing intricacies, which some companies face, was in place, too. "One of the existing complexities is connected with generic drugs. For generic drugs, companies still have to repeat the earlier-conducted trials (bioequivalence) in Russia, as well. . Foreign Companies have to organize additional money for an additional trial to register their generic drug. This is how it works now." - says Natala.

Find more at cebiotech.com

OCT will conduct additional pre-clinical studies and a bioequivalence trial of an oncology drug for an integrated healthcare multinational company.
Certain additional pre-clinical data should be obtained prior to the initialization of the bioequivalence trial, namely, the results of acute and sub-acute toxicity studies. This usually takes no more than 2,5 - 3 months, including the import of the drug, studies themselves, report preparation, etc. These studies are usually conducted on mice and rats. The primary goal of acute and sub-acute toxicity study is to obtain data on the toxicity of the new generic product. These data will be later included into the registration dossier and submitted to regulatory authorities for their review before the bioequivalence study is launched.

After these activities have been completed, OCT will initiate the bioequivalence study, in which OCT will be responsible for all the activities: logistics issues, documents design, review and translation, clinical trials application and regulatory authorities approval, conduct of the clinical part and analytical services, clinical data management, statistical analysis, and final report preparation.

The investigational product is a drug used for the treatment of certain cancer forms. It acts by inhibiting a certain enzyme in cancer cells (and not destroying all cells, which divide quickly). The drug is usually used in the treatment of the following diseases - gastrointestinal stromal tumors, chronic myelogenous leukemia and other cancers. It can also be used in aggressive systemic mastocytosis without c-Kit mutational status or with c-Kit mutational status unknown, relapsed or refractory Ph-positive ALL, etc.

The purpose of the trials is to obtain the drug registration in the Russian Federation. Chronic myelogenous leukemia is one of the most widespread leukosis among adults. There are more than 14 000 patients in Russia diagnosed with this diseases, and, unfortunately, this figure adds roughly 3 000 new cases each year. Average age of such patients is 55. The access of leukemia and patients to new drugs and therapies with proved efficacy should help resist the disease and try to improve patients` quality of life.

OCT will assist a top ten pharmaceutical company with consultancy activities. This Company has been actively entering the Russian medicinal products market, which requires a full understanding of how it functions, under which regulations the market is developing, in what way legislative provisions should be implemented, etc.

The Company develops and markets new branded original drugs and generic products, both OTC as well as Rx, medical devices. Taking into account the great variability of the products, one should fully understand the way these products come to the registration in Russia. The following cornerstone legislative provisions constitute the basis for clinical trials of drugs:

• Federal Law No. 61-FZ “On circulation of medicines” as of April 12, 2010
• GOST R 52379-2005 “Good clinical practice”
• Guidelines on Bioequivalence Assessment of Medical Drugs as of 2008
• ICH-GCP Guidelines
• US Code Federal Regulations, CFR Title 21 Food & Drug Administration revised as of April 1, 2006
• and other applicable legislation, which also regards the important issues of patients / volunteers insurance, ethics provisions, import and export of study drugs / concomitant medication / biosamples, accreditation of medical institutions, quality control activities and measures, etc.

OCT has highly-qualified and widely experienced specialists in the following spheres and departments:

• medical writing and scientific questions;
• regulatory affairs;
• logistics issues;
• project managers and monitors – doctors, who have valuable experience in certain therapeutic areas, which enables their expertise also to be considered while choosing the right path for further drug development.

OCT has been granted a Phase II, randomized, multi-centre, open-label, active-controlled, dose-finding trial in women with breast cancer receiving myelotoxic chemotherapy. Myelotoxicity in this study will be defined by the duration of moderate neutropenia.

Neutropenia is a granulocyte disorder. The disease is characterized by a low number of neutrophils, which is the most important type of white blood cell. Neutrophils account for 50-70% of circulating white blood cells. Neutrophils serve as the primary defense against infections – they destroy bacteria in the blood. Patients with neutropenia are regarded as more susceptible to bacterial infections, which could cause life-threatening conditions. Standard therapy for neutropenia is recombinant G-CSF (granulocyte-colony stimulating factor) such as filgrastim.

As for the study drug, this will be a recombinant fusion protein with human G-CSF fused to human immunoglobulin IgG2-Fc. The product is delivered by a subcutaneous injection.

This phase II open label clinical study will enroll 200 women with stage II - III invasive breast cancer in up to 35 clinical centers in North America and Europe that will receive chemotherapy treatment.

In OCT countries, namely Russia and the Ukraine, 130 patients will be enrolled within 6 months at 16 investigational sites providing the highest recruitment rate regionally.

The trial will be conducted in compliance with the trial protocol, ICH-GCP Guidelines, and US Code Federal Regulations, CFR Title 21 Food & Drug Administration revised as of April 1, 2006.

This will be a full-service support clinical project, including project management, site selection, clinical monitoring, warehousing, study materials purchase and other logistics assistance, safety management, regulatory activities within the clinical trial approval and export/import licenses obtainment, final report preparation, investigator’s meeting organization, others. The leading international laboratory will be used for biosamples assessment. Total study duration will be around 15 months.

The clinical project is the result of repeat business. OCT will perform the study for an ambitious Chinese pharmaceutical company entering foreign markets. We are glad to expand our partners’ network in all the regions worldwide.

OCT has a great experience in oncology clinical development. OCT will be happy to provide the highest quality level of clinical services.

OCT has won a tender for conducting an open-label randomized single-center three-period single-dose bioequivalence study in healthy volunteers of a fixed combination investigational drug with the appropriate reference products.

The study will be performed in accordance with GOST R 52379-2005 “Good clinical practice”, Federal Law No. 61-FZ of 12.04.2010 “On circulation of medicines”, Bioequivalence Assessment of Medical Drugs Guidelines of 2008,
and other applicable legislation.

The investigational product is a new unique painkiller combination of ibuprofen and paracetamol. The drug is indicated for the temporary relief of mild to moderate pain associated with migraine, headache, backache, period pain, dental pain, rheumatic and muscular pain, pain of non-serious arthritis, cold and flu symptoms, sore throat and fever. This product is especially suitable for pain which requires stronger analgesia than it is reached within monotherapy by means of ibuprofen or paracetamol.

The study drug is formulated using a unique patented technology, by means of which the active ingredients are dissolved rapidly in the stomach and are able to deliver a “combination effect” of two actives with opposing dissolution profiles.

The study will be placed at the leading certified Phase I investigational center. 28 healthy volunteers will be randomized within the PK trial.

For OCT this will be a full-service project including medical writing, regulatory and logistics support, project management and administration, quality assurance, clinical monitoring, pharmacovigilance, data management and biostatistics, final BE and statistical report preparation.

The leading Russian analytical laboratory will be involved in this bioequivalence study . The special analytical method will be developed, validated, and used in the trial.

OCT will be glad to support its Client within the clinical study, which is aimed to register the generic product in Russia.

We are proud that this is the second project requested by the same Sponsor – one of the leading UK life science companies.

OCT will be attending Russian Pharmaceutical Forum 2012 in St. Petersburg. OCT is a regional CRO operating in Russia, Ukraine, Belarus, Bulgaria, Baltic Countries, Poland and Czech Republic. To set up a meeting, please contact us. OCT will be represented at Russian Pharmaceutical Forum 2012 by:

Julia Sardaryan,

Head Business Development

OCT will be attending the 5-th Annual CEE & CIS Clinical Trials Forum in Vienna on April 18-19, 2012. If you are looking for a CRO partner to conduct clinical trials in Russia, Ukraine, Bulgaria, Belarus, Latvia, Lithuania, Estonia, Poland and Czech Republic we would be glad to discuss our potential collaboration with you. To set up a meeting, please contact us. OCT will be represented at CEE and CIS Forum 2012 by:

Julia Sardaryan

Head Business Development,

We are happy to announce that OCT signed an agreement with a top ten pharma to provide consultancy services.

In accordance with the agreement OCT is going to provide regulatory affairs advice at all stages of product development, from the early concept stage, through product development, up to and beyond submission of a dossier for marketing authorization in Russia.

It is well known that current legislation in Russia caused a lot of concerns and questions from Russian and international companies. On April 12, 2010 the President of the Russian Federation signed the new Federal Law “On the Circulation of Medicines” (the “New Law”) thus completing the procedure of its adoption. The New Law was to replace the existing Federal Law No. 86-FZ “On Medicines” dated June 22, 1998, as amended (the “Law on Medicines”). The law introduced several dramatic changes. The law aimed at improving regulatory environment in the Russian Federation but it turned out to be a big issue for pharmaceutical industry. The law still causes a lot of questions and controversies.

OCT will provide regulatory input into the client’s product development strategy.

It is well known that the key to any successful regulatory strategy is a fruitful interaction with the relevant regulatory agency. OCT-Clinical trials in Central and Eastern Europe is a local expert that has good connections and relations with regulators and experts in Regulatory Authorities in Russia. OCT is happy to assist the client interpret current Russian legislation and find solutions for a more rapid drug development and registration. We will provide our client with different regulatory scenarios to speed up market authorization.

OCT are very glad to assist our client seek advice and opinions of regulators and experts in Russia