| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute bacterial sinusitis |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060841 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Main objective :To characterize the pharmacokinetics of azithromycin in maxillary sinus aspirate and in serum in adult subjects with acute bacterial sinusitis after treatment with azithromycin IR 500 mg orally, once daily for three days, or a single 2.0 g oral dose of azithromycin microspheres, for acute bacterial sinusitis.
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| E.2.2 | Secondary objectives of the trial |
Secondary objectives :
1. To quantify the rate and extent of bacterial eradication (disappearance of original strains) during Day 1-5 visits for each formulation
2. To assess clinical efficacy for each formulation
3. To assess bacteriologic efficacy for each formulation
4. To assess the safety and tolerability of each formulation
5. To explore possible relationships between pharmacokinetics and bacteriologic/clinical responses.
6. To estimate the pharmacokinetics exposure (AUC24) of azithromycin SR formulation compared to azithromycin IR formulation in maxillary sinus aspirate.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Written informed consent of the subject or a legally authorized representative (as outlined in Appendix A,Section 2.2).
2. Male or female subjects, 18 years of age or older.
3. A clinical diagnosis of acute bacterial sinusitis as demonstrated by presence of the following cardinal signs and symptoms for a minimum duration of 7 days but not more than 28 days:
a. Facial pain, pressure and/or tightness over one or both maxillary sinuses, and/or pain in one or both maxillary areas that worsens with movement or percussion, and
b. Presence of one or more of the following signs:
i. purulent nasal discharge
ii. purulent drainage in the posterior pharynx
iii. purulent discharge from the maxillary sinus orifice
4. A positive sinus x-ray* Waters’ View confirming sinusitis:
For all countries, excluding Germany: A sinus radiograph (X-ray) must show at least one of the following in one or both maxillary sinuses:
a. Complete or partial opacification
b. A ≥ 5mm air/fluid level
For Germany only: A sinus radiograph (X-ray), which was performed independently of the trial for clinical reasons (i.e., to diagnose sinusitis), must show at least one of the following in one or both maxillary sinuses:
a. Complete or partial opacification
b. A ≥ 5 mm air/fluid level
*At sites where the local standard of care may require a computerized tomography (CT) scan to confirm, or is needed to make a diagnosis, the CT scan, which confirms the presence of sinusitis may be substituted in place of a sinus X-ray.
5. Two or more of the following clinical signs/symptoms must be present:
a. Fever, as defined by: oral temperature: ≥ 38°C or ≥ 100.4°F, or tympanic temperature: ≥ 38.5°C or ≥ 101.2°F
b. Leukocytosis (WBC > 10,000/mm3 or ≥ 15% band forms)
c. Frequent coughing
d. Headache
e. Nasal congestion
f. Post-nasal drainage
6. Subjects must be willing to undergo direct aspiration of the sinus cavity by puncture with the SinoJect™.
7. Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test within 48 hours prior to start of study medication. Women of childbearing potential must use a highly effective method of birth control/ contraception such as combined oral hormonal hormonal contraceptionves, implantable contraceptive (e.g., Norplant), injectable contraceptive (e.g., Depo-Provera), medicated hormone releasing intrauterine devices, or sexual abstinence, or vasectomized partner, throughout the study and for four weeks after completion of the study. Women who have been surgically sterilized or are at least two years postmenopausal may be enrolled and do not need to use birth control. Women whose method of birth control is combined oral hormonal contraceptives are required to practice sexual abstinence during the study and for one month following the completion of the study.
8. Subjects who are willing and able to comply with scheduled study visits, treatment plan, laboratory tests and other trial procedures. |
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| E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the trial:
1. Previously diagnosed disease(s) of immune function, including:
a. Subjects with a baseline absolute neutrophil count less than and equal to 1000/mm3
b. HIV positive subjects with a CD4 count less than and equal to 200/mm3,
and/or
c. Any immunoglobulin or neutrophil disorder.
2. Pregnant or lactating women
3. Abnormal prothrombin time or any other clinically significant laboratory abnormality
4. Concomitant illnesses requiring anti-infective therapy that might interfere with evaluation of a therapeutic response within 5-7 days (azithromycin, ceftriaxone) or 48 hours (any other antibiotic) prior to the baseline visit. Subjects receiving a systemic antifungal or antiviral agent for prophylaxis or for treatment of a non respiratory infection (e.g., for vaginal yeast infection or HSV) are eligible for study entry and may continue those medications.
5. Gastrointestinal disturbances that might affect drug absorption (e.g., malabsorption syndromes, peptic ulcer, acute diarrhea)
6. Symptoms of sinusitis( including those decribed in the inclusion criteria above) lasting longer than 28 days.
7. Four or more episodes of acute sinusitis within the preceding 12 months or a history of chronic sinusitis or allergic fungal sinusitis
8. Nasal or sinus surgery within three months prior to enrollment other than for a diagnostic procedure
9. Complicated rhinosinusitis (e.g., osteomyelitis, Pott’s puffy tumor, malignancy involving the sinus, or the requirement for reconstructive surgery). Subjects with significant nasal obstruction due to septal deviation or nasal polyposis.
10. Subjects who are currently hospitalized for any reason
11. Nosocomial rhinosinusitis
12. Diagnosis of cystic fibrosis
13. Severe renal insufficiency (creatinine clearance CrCl, < 30 ml/min)
14. Known or suspected hepatic disease
15. Treatment with an investigational drug within 30 days prior to trial enrollment.
16. Prior enrollment in either this or any trial utilizing azithromycin microspheres.
17. Subjects who regularly takes magnesium or aluminum containing antacids.
18. Subjects taking any immunosuppressant medication, coumadin or other anticoagulant medication (e.g., aspirin and other non-steroidal anti-inflammatory drugs).
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of the trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
20. Positive urine drug screen. Subjects with history or are current abusers of alcohol and/or other drugs.
21. Know or suspected hypersensitivity or intolerance to any macrolide-like compound, including erythromycin, clarithromycin, and azithromycin. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Characterization of azithromycin pharmacokinetics in maxillary sinus aspirate and simultaneously collected serum after treatment with azithromycin IR 500 mg orally, once daily for three days, or a single 2.0 g oral dose of azithromycin microspheres. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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