Temporary relief of cold and flu symptoms, i.e. mild to moderate pain, sore throat, fever and nasal congestion MedDRA version: 20.1 Level: LLT Classification code 10009851 Term: Cold System Organ Class: 100000004862 MedDRA version: 21.1 Level: LLT Classification code 10022009 Term: Influenza-like symptoms System Organ Class: 100000004867
Conditions
Interventions
Product Name: FDC Ibuprofen, Paracetamol, Phenylephrine Hydrochloride
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ibuprofen
CAS Number: 15687-27-1
Concentration unit: mg milligram(s)
Sponsors
PharOS Pharmaceutical Oriented Services Single Member Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Subjects willing and able to provide voluntary written informed consent. [2] Male or female subjects aged between 18 and 60 years inclusive on the date of consent. [3] Diagnosis of common cold/flu-like syndrome defined as presence of at least two of the following symptoms of at least moderate severity on 4-point symptom severity scale (1=no; 2=mild; 3=moderate; 4=severe): cough, throat discomfort, nasal obstruction, myalgia, fever and head congestion. [4] Subjects with presence of the following at inclusion: a. Mild to moderate pain defined as overall pain NRS score in between = 4 to = 6 (at a 0 to 10 Likert scale) by the subject. b. At least = 38°C axillary armpit body temperature. c. Nasal obstruction with a total nasal airflow resistance (NAR) of >0.25 Pa/cm3 second as determined by posterior rhinomanometry. [5] Onset of symptoms =48 hours prior to screening visit. [6] Subjects who are tested negative for rapid antigen test for COVID-19 within 15 days prior to screening or who are vaccinated (at least one dose) against COVID- 19 at least 15 days prior to screening. [7] Male subjects who agree to use effective contraception during treatment and for 4 weeks after the last investigational product dose. [8] Female subject of childbearing potential (not surgically sterilized/ hysterectomized or postmenopausal for at least 1 year) who agree to use reliable methods of contraception for the entire trial duration and for 4 weeks after the last investigational product dose. [9] Willing to avoid alcohol, smoking, coffee and chewing tobacco products during the study period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [1] History of hypersensitivity or intolerance to the active substances or any of the excipients of the trial medications. [2] Known previous hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs. [3] Diagnosis / history of any other infectious disease that produces also symptoms of common cold but needs specific treatment with antibacterial or antiviral drugs (e.g. bronchitis, pneumonia etc.). [4] Subject with any of the following conditions a. Hyperthyreosis b. Pheochromocytoma c. Narrow angle glaucoma d. Severe liver failure (Child- Pugh score > 9) e. Severe renal failure f. Congenital elevated bilirubin level in the blood (Gilbert’s syndrome or Meulengracht’s disease) g. Severe cardiovascular disease, severe cardiac arrhythmia, and uncontrolled hypertension h. Asthma bronchiale, chronic obstructive pulmonary disease, respiratory depression or insufficiency i. Allergic rhinitis j. Glucose-6-phosphate and dehydrogenase deficiency k. Narrowing of the upper urinary tract or prostate hyperplasia with residual urine l. Porphyria m. Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding). n. History of gastrointestinal bleeding or perforation related to previous nonsteroidal anti-inflammatory drug therapy o. Active corona virus disease (COVID-19) according to PCR or rapid Antigen test p. Clinical evidence of immunosuppression. [5] Concomitant or recent (within last 14 days before screening) use of tricyclic antidepressants and MAO-inhibitors, MAO-inhibitors, SSRIs, SNRIs or Lithium. [6] Subjects under treatment with anticoagulants including warfarin etc. [7] Changes in existing concomitant therapy with corticosteroids, or other drugs with influence on the immune system (e.g. immunosuppressive or cytostatic agents). [8] Any other continuous drug treatment of symptoms of common cold and flu (except analgesic rescue medication intake e.g. 500 mg of metamizole for pain relief). [9] Pregnant or breast-feeding female subject. [10] Female subject of childbearing potential (not surgically sterilized/ hysterectomized or postmenopausal for at least 1 year) who is not currently using (documented at screening visit) and not willing to use medically reliable methods of contraception for the entire trial duration such as oral, injectable or implantable contraceptives, intrauterine contraceptive devices (IUD), sexual abstinence or vasectomized partner. [11] Any other condition of the subject (e.g. serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize subject’s safety, compliance or adherence to protocol requirements. [12] Participation in any research study involving another investigational medicinalproduct (IMP) within 30 days prior to screening visit, or simultaneous participation in another clinical study or previous participation in present study. [13] Suspected alcohol/ drug dependence or abuse (including heavy smoking: = 20 cigarettes daily). [14] Subjects with known positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV). [15] Subjects with eating disorders, cystic fibrosis, or on a controlled sodium diet. [16] Subjects with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucras
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of the FDC product containing 200 mg ibuprofen, 500 mg paracetamol, and 10 mg phenylephrine hydrochloride per film-coated tablet administered as 2 tablets PO TID compared to two reference products: Doregrippin® (containing 500 mg paracetamol and 10 mg phenylephrine hydrochloride per coated tablet) administered as 2 tablets PO TID and Nurofen® (containing 200 mg ibuprofen per coated tablet) administered as 2 tablets PO TID for a duration of 7 days, for the temporary relief of cold and flu symptoms, i.e. mild to moderate pain, sore throat, fever and nasal congestion.;Secondary Objective: 1. To demonstrate the superiority of the FDC product containing 500 mg paracetamol, 200 mg ibuprofen, and 10 mg phenylephrine per tablet versus placebo for the temporary relief of cold and flu symptoms, i.e. mild to moderate pain, sore throat, fever and nasal congestion. 2. To demonstrate the superiority of each of the reference products Doregrippin® (containing 500 mg paracetamol and 10 mg phenylephrine per tablet) and Nurofen® (containing 200 mg ibuprofen per tablet) versus placebo for the temporary relief of cold and flu symptoms, i.e. mild to moderate pain, sore throat, fever and nasal congestion. 3. To assess the safety and tolerability of the investigational product (i.e. the FDC) as compared to the two reference products. 4. To assess the safety and tolerability of the investigational product (i.e. the FDC) as compared to the placebo.;Primary end point(s): 1. Mean change of nasal airflow resistance as determined by posterior rhinomanometry from baseline to 4.0 hours after first dose on day 1 of treatment. 2. Mean change of subjective intensity of nasal congestion using a 4-point scale (1=no, 2=mild, 3=moderate, 4=severe) from baseline to 4.0 hours after first dose on day 1 of treatment. 3. Mean change in overall pain score from baseline to end of study (day 8+1) 4. Mean change in axillary armpit temperature from baseline to end of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Mean change of nasal airflow resistance as determined by posterior Rhinomanometry from baseline to 0.5, 1.0, 2.0 and 3.0 h after first dose on day 1. 2. Mean change of subjective intensity of nasal congestion using a 4-point scale (1=no, 2=mild, 3=moderate, 4=severe) from baseline to 0.5, 1.0, 2.0 and 3.0 h after first dose. 3. Mean change in overall pain score from baseline to day 1 (0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 h), day 2, 3, 4, 5, 6 and 7. 4. Mean change in Headache pain score from baseline to day 1 (0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 h), day 2, 3, 4, 5, 6 and 7. 5. Mean change in Throat pain score from baseline to day 1 (0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 h), day 2, 3, 4, 5, 6 and 7. 6. Mean change in Muscle pain score from baseline to day 1 (0.5, 1.0, 2.0, 3.0, 4.0 and 6.0 h), day 2, 3, 4, 5, 6 and 7. 7. Mean change in axillary armpit temperature from baseline to day 1 (1.0, 3.0, 4.0 and 6.0 h) day 2, 3, 4, 5, 6 and 7. 8. Mean change in Wisconsin Upper Respiratory Symptoms Survey-21 (WURSS-21) from baseline to day 2, 3, 4, 5, 6 and 7. 9. Mean reduction in axillary armpit temperature at 1.0, 3.0, 4.0, and 6.0 h after first dosing on day 1. 10. Wisconsin Upper Respiratory Symptoms Survey-21 (WURSS-21) sub group analysis on Day 1, 2, 3, 4, 5, 6, and 7 11. Axillary armpit temperature sub group analysis on Day 1, 2, 3, 4, 5, 6, and 7. 12. Overall pain score sub group analysis on Day 1, 2, 3, 4, 5, 6, and 7. 13. Number and proportion of patients requiring rescue analgesic treatment during 6.0 h after first drug administration on day 1. 14. Duration of pain relief defined as the time to reach a main intensity score < 3 on a 0 to 10 pain intensity scale or the time to rescue analgesic intake. 15. Number and proportion of patients requiring rescue analgesic treatment during the study. 16. Time before rescue analgesic treatment intake. 17. Time to reduce the axillary armpit temperature below 38.0°C.;Timepoint(s) of evaluation of this end point: 1. | — |
Countries
Bulgaria
Contacts
Public ContactProject Manager
PharOS Pharmaceutical Oriented Services Single Member Ltd.
Outcome results
None listed