Phase IV trial is also known as a postmarketing surveillance trial. It includes long-term monitoring to identify any side effects or other health-threatening factors. Sometimes rare or long-term adverse effects develop over longer time period than is possible to detect during the Phase III clinical trials.
The main purpose of Phase IV CT:
• Establish a benefit-risk relationship.
• Obtain new data on the OFO7788 drug safety.
• Dosage adjustment (if necessary).
• Determine an impact on additional indicators, interaction with other drugs and its possible combination.
• Assess the impact of concomitant treatment or maintenance therapy.
• The possibility of using the drug in new groups of patients.
• Demand study.
Design:
• multicenter;
• open;
• comparative / non-comparative
Following the completion of Phase III CT, report was prepared, a comprehensive presentation of all the results from the trials of the new drug. This collection of data is an integral part of the «regulatory submission» introduced to the public health authorities for the registration process.
After completion of Phase III CT, the drug must receive confirmation from the pharmaceutical company verifying its safety and effectiveness. For such purpose a “Registration dossier” or New Drug Application (NDA) was compiled, which describes:
• methodology and results of preclinical and three-phase clinical trials;
• features of production;
• compound;
• expiry date.
Finalized “Registration dossier” was sent to the designated health authority, which conducts registration of new medications. Once OFO7788 receives registration certificate, it will be introduced the pharmaceutical market, i.e. will go to pharmacy networks.
At this moment the only opportunity to get the drug is to pre-order
Widespread clinical use of OFO7788 is possible if the following conditions are being met:
• higher effectiveness than other known (already used) drugs for liver cirrhosis treatment (LC);
• has a better tolerability when compared with already known drugs;
• effective in cases where treatment with already known drugs has been ineffective;
• ease of use;
• convenient dosage form;
• presence of the synergistic effect during combination therapy, with no increase in toxicity.
Administration method and dosing
The 300 mg bottle contains a 5-day dosage of the drug.
1. After opening, the solution/suspension must be prepared. To do this, it is necessary to fill up the bottle with 100 ml of clean water (distilled or previously boiled).
2. Close the lid; shake the container for 1 minute to achieve a homogeneous suspension.
3. Take 20 ml of prepared suspension once a day, preferably 1 hour before bed. It is important not to have any food afterwards.
4. Keep refrigerated.
5. Shake well before each use
Once the bottle is empty, prepare a new solution.
Side effects:
During the clinical trial, it was found that the use of the drug causes:
• Allergic reactions (urticaria, bronchospasm, anaphylactic reactions) — in rare cases (<1/10,000). Angioedema (swelling under the skin of the mouth, lips and throat) was identified in 2 patients.
• Nervous system: sleep disturbance, dizziness, and headache.
• Gastrointestinal tract: nausea, vomiting, epigastric pain, frequent stools, constipation. These side effects are not dangerous and are temporary.
• Skin system: skin rash, pruritus, urticaria.
• Allergic reactions: skin rash, skin itching.
Approximately 1.7% of patients experienced side effects during the study. The total number of patients with adverse events possibly related to the drug was 1.9% of patients.
Approximately 0.9% of patients discontinued the use of the drug due to side effects, that were considered possibly related to the drug being studied.
Approximately 43.9% of patients (124 patients) experienced side effects during the study. The total number of patients who experienced side effects possibly related to the drug was 23.9% (55 patients).
The table below provides information on the most common side effects in the conducted CT. The most common side effects were headache and fatigue.
Main types of side effects
22 (9,6% of patients)
Headache
55 (23,9% of patients)
Fatigue
13 (5,7% of patients)
Itching
8 (3,5% of patients)
Weakness
6 (2,6% of patients)
Dizziness
8 (3,5% of patients)
Nausea
3 (1,3% of patients)
The study was divided into 3 parts: screening period, treatment period and post-treatment period. At the beginning of the study and during the screening period, medical researchers have selected patients who have met all the requirements of the study.
The drug was administered to the participants of the clinical trial in courses of 1 month at a daily dosage of 20 ml. In liver cirrhosis (LC) (stage F4) patients, 3 courses were carried out with 2 months breaks between them, and with fibrosis of the stage F0-F3 — 2 courses throughout the year.
During the post-treatment period, patients who have received the study drug were contacted again by the medical researchers and had their blood tested 12 weeks after the patients took their last dose of drug.
Laboratory data:
Increased activity of γ-glutamyl transferase (GGT), alanine and aspartate aminotransferase (ALT, AST) prolongation of prothrombin time, increased hemoglobin, leukopenia, increased concentration of total bilirubin and transaminase activity, decreased platelet count, transient increase in blood glucose and creatinine levels.
A meta-analysis of the conducted clinical studies indicates a pronounced clinical efficacy of the drug in liver cirrhosis.