Fixed-dose Combination of 1000 mg Dipyrone Monohydrate + 60 mg Caffeine + 4 mg Chlorpheniramine Maleate in Improving Symptoms of the Common Cold and Flu in Adults

A Phase III, Multicenter, Double-blind, Randomized, Parallel-group Non-inferiority Clinical Trial to Evaluate the Efficacy and Safety of a Fixed-dose Combination of 1000 mg Dipyrone Monohydrate + 60 mg Caffeine + 4 mg Chlorpheniramine Maleate Compared to Benegrip® in Improving Symptoms of the Common Cold and Flu in Adult Participants

Phase III clinical trial to evaluate the efficacy and safety of a fixed-dose combination of 1000 mg dipyrone monohydrate + 60 mg caffeine + 4 mg chlorpheniramine maleate in improving symptoms of the common cold and flu in adults.

Inclusion Criteria:

• The following criteria must be met for the participant to be included in the study:

  1. Participants of both sexes, aged between 18 and 60 years.

  2. Be able to understand, agree to participate in the study, comply with procedures, and attend visits, as indicated by signing the informed consent form (ICF) approved by the Ethics Committee.

  3. Present symptoms of nasal obstruction and/or congestion due to the common cold or influenza, with onset within less than 48 hours, with symptoms classified by the participant as moderate to severe on a 4-point scale (0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms).

  4. Must not have used any medication for symptomatic treatment of the condition.

  5. Female participants without childbearing potential, defined as postmenopausal women (defined as 12 months or more of amenorrhea) or those who have undergone surgical sterilization*, OR female participants with reproductive potential who agree to use a reliable contraceptive method**.

     * Female sterilization (bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation performed at least 6 weeks before administration of the investigational product.

     ** If the participant is of childbearing potential and decides to participate in the study, she must use or request that her partner use a reliable contraceptive method. Reliable contraception is defined as the use of at least one of the following: condoms, diaphragm, and/or hormonal contraceptive methods (estrogenic and/or progestogenic), including oral, vaginal, injectable, transdermal, implantable, and intrauterine devices. Only participants who explicitly declare no risk of pregnancy, either due to not engaging in sexual activity or engaging exclusively in non-reproductive practices, may participate without mandatory contraceptive use; for example: participants with a sterile or vasectomized partner (at least 6 months before screening), or total heterosexual abstinence.

     Exclusion Criteria:

• A positive response to any of the following criteria will exclude the participant from the study:

  1. Participants with COVID-19, diagnosed by rapid antigen test and/or RT-PCR for SARS-CoV-2;

  2. Previous contact with individuals diagnosed with COVID-19 within 14 days prior to screening;

  3. Vaccination against influenza and/or COVID-19 within 7 days prior to the study;

  4. Presence of gastrointestinal symptoms and/or dyspnea associated with cold or flu symptoms;

  5. Clinical history consistent with bacterial upper respiratory tract infection requiring antibiotic therapy;

  6. History of grade II or III septal deviation, nasal polyps, marked turbinate hypertrophy, adenoid hypertrophy, chronic sinusitis (or recent episode within the last 2 weeks), rhinitis (seasonal allergic, drug-induced, vasomotor, atrophic, or other), or other conditions causing nasal obstruction;

  7. Diagnosis of: congenital glucose-6-phosphate dehydrogenase deficiency, prothrombin deficiency, gastroduodenal ulcer, hepatic porphyria, narrow-angle glaucoma, chronic nephritis, blood dyscrasias, asthma, chronic respiratory infection, chronic respiratory disease, severe cardiocirculatory conditions, or immunocompromised status;

  8. History of hypersensitivity to analgesics, antirheumatic drugs, and/or alcoholic beverages;

  9. Participants allergic to foods, hair dyes, and/or preservatives;

  10. Participants dependent on decongestants (topical, nasal, or oral) or receiving allergen-specific immunotherapy;

  11. Use of monoamine oxidase inhibitors (phenelzine, iproniazid, isocarboxazid, harmaline, nialamide, pargyline, selegiline, toloxatone, tranylcypromine, moclobemide), cyclosporine, chlorpromazine, barbiturates (phenobarbital, thiopental, methohexital, pentobarbital), hypnotics (triazolam, midazolam, oxazepam, chlordiazepoxide, clonazepam), narcotic analgesics (morphine, codeine, meperidine), sedatives, and/or tranquilizers;

  12. History of alcoholism (average alcohol intake exceeding 3 standard drinks* in a single day or more than 7 drinks per week for women, and more than 4 drinks in a single day or more than 14 drinks per week for men);

      • One standard drink is defined as: one can of regular beer (330 mL at 4%); one serving of distilled spirits (30 mL at 40%); one glass of wine or small glass of sherry (100 mL at 12% or 70 mL at 18%); one small glass of liqueur or similar (50 mL at 25%).

  13. Pregnant or breastfeeding women, or those intending to become pregnant during the study period;

  14. Participation in a clinical study within the last 12 months, at the investigator's discretion;

  15. Any condition that, in the physician's judgment, may interfere with participation in the study.