| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Seasonal Allergic Rhinitis |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039776 |
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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 |
| The primary objective of this study is to evaluate the effect on nasal congestion of a maximally tolerated dose of SCH 497079, when taken in combination with DL 5 mg (identified in Phase 1 studies), in subjects with seasonal allergic rhinitis (SAR) who have been exposed to pollen in the VCC. This objective will be accomplished by comparison of the effect on nasal congestion, over the 7.5 hour observation period, of the coadministration of DL 5 mg and SCH 497079 100 mg with that of DL 5 mg taken alone. |
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| E.2.2 | Secondary objectives of the trial |
Key secondary objectives include calculation of the estimates of the following treatment differences over the 7.5-hour observation period and at each time point:
The comparison of the effect on nasal congestion of the coadministration of DL 5 mg and SCH 497079, at a 20 mg dose, with that of DL 5 mg taken alone.The comparison of the effect on nasal congestion of DL 5 mg, taken in combination with each of two dose levels of SCH 497079, 100 mg and 20 mg, versus concurrent administration of DL plus PSE 240 mg. Evaluation of the safety profiles among the five treatments of postdose vital signs and adverse events compared with predose evaluations. Single dose plasma SCH 497079, DL 3-OH DL, and pseudoephedrine concentrations and pharmacokinetic parameters will be listed and summarized using means, and percent coefficients of variation. In addition, an association between plasma concentrations and observed decongestant activity will be explored if the data allow.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Subjects must be willing to give written informed consent and adhere to dose and visit schedules.
2. Subjects must have the appropriate washout times from the prohibited medications (see Section 7.4.2.1.1).
3. Clinical laboratory tests (CBC, blood chemistries, urinalysis) at screening must be within normal limits or clinically acceptable to the investigator.
4. Subjects must skin test positive confirming hypersensitivity to Dactylis glomerata grass allergen extract which is cross reactive with pollen mixture used in the chamber, unless a positive test was obtained within the previous 12 months. IgE-mediated hypersensitivity must be documented by a positive response to the skin prick test with wheal diameter 3 mm larger than diluent control.
5. Female subjects of childbearing potential must have a negative serum pregnancy test prior to treatment with study medication; a negative urine pregnancy test must be obtained at least every 28 days during study participation. Female subjects of childbearing potential must be using a medically accepted method of birth control (eg, double barrier method, oral contraceptive, Depo-Provera, or Norplant) prior to Screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy or tubal ligation). Women of childbearing potential should be counseled in the appropriate use of birth control while in this study. Women who are not currently sexually active must agree and consent to use one of the medically accepted methods of birth control if they become sexually active while participating in the study.
6. Subjects must have the following minimum symptom scores using a 0-3 scale at some point during each of the 120-minute screening period challenge sessions:
a. Nasal Congestion Score of at least 2;
b. Total Nasal Symptoms Score of at least 6 (symptoms are nasal congestion, nasal itching, sneezing, and rhinorrhea);
c. Total Non-nasal Symptoms Score of at least 2 (symptoms are itching/burning eyes, tearing/watering eyes, and itching of ears/palate.
7. Subjects must be in good health and free of any clinically significant disease (other than SAR) that would interfere with the study schedule or procedures, or compromise the subject’s safety.
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| E.4 | Principal exclusion criteria |
1. Female subjects who are pregnant, intend to become pregnant during the study, or are nursing.
2. Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
3. Subjects who have used any investigational drugs, including placebo, within 30 days of study entry.
4. Subjects who are participating in any other clinical study.
5. Subjects who are part of the staff personnel directly involved with this study.
6. Subjects who are family members of the investigational study staff directly involved with this study.
7. Subjects who had an upper or lower respiratory tract infection within 4 weeks before screening, or who have a respiratory infection any time during the treatment phase of the study.
8. Subjects who have nasal structural abnormalities, including large nasal polyps or marked septal deviation, that significantly interfere with nasal airflow.
9. Subjects who have been previously enrolled (ie, signed informed consent) into this study.
10. Subjects with rhinitis medicamentosa.
11. Subjects with a history of anaphylaxis or severe or serious reaction to skin testing.
12. Subjects who have a known potential for hypersensitivity, allergy, or idiosyncratic reaction to any of the study drugs or excipients.
13. Subjects who, in the opinion of the investigator, are dependent upon nasal, oral, or ocular decongestants, nasal topical antihistamines, or nasal steroids.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable is the subjectively evaluated symptom of nasal congestion. The nasal decongestant effect is expressed as an average change from Baseline over the 7.5-hour evaluation period. The primary comparison for this variable is SCH 497079 100 mg plus DL 5 mg taken in combination vs DL 5 mg taken alone.
Pairwise comparisons will be made using linear contrasts of the treatment means obtained from an analysis of variance model that extracts sources of variation due to treatment, subject, and phase.
Summary statistics for the primary variable will be provided for the subject subgroups of sex and race (Caucasian and non-Caucasian).
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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 | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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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| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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