| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Vasomotor/Idiopathic Rhinitis |
|
| MedDRA Classification |
| 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 compare the efficacy and safety of GW685698X 100 mcg once daily (QD) aqueous nasal spray with vehicle placebo nasal spray in adult and adolescent subjects (≥ 12 years of age) with vasomotor rhinitis (VMR)/idiopathic rhinitis (IR). |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subject will be eligible for inclusion only if all of following criteria apply:
1. Informed consent
• Subject has provided an appropriately signed and dated informed consent. An
appropriately signed and dated assent must be obtained from the parents or
guardian if the subject is a child under 18 years of age.
2. Subject is treatable on an outpatient basis.
3. Age - ≥ 12 years at Visit 2
4. Male or eligible female
To be eligible for entry, females of childbearing potential must commit
to consistent and correct use of an acceptable method of birth control, as defined
by the following:
• Male partner who is sterile prior to the female subject’s entry into study and
is sole sexual partner for that female subject
• Implants of levonorgestrel
• Injectable progestogen
• Oral contraceptive (either combined estrogen/progestin or progestin only)
• Any intrauterine device (IUD) with a documented failure rate of less than 1%
per year, or
• Females of childbearing potential who are not sexually active must commit to
complete abstinence from intercourse for 2weeks before exposure to the
study drug, throughout the clinical trial, and for a period after the trial to account
for elimination of the drug (minimum of six days).
• Double barrier method – spermacide plus a mechanical barrier (e.g., spermacide
plus a male condom or a spermacide and female diaphragm).
Female subjects should not be enrolled if they plan to become pregnant during the
time of study participation. A serum pregnancy test will be performed at screening
visit and final/early withdrawal visit. A urine pregnancy test will be performed at
randomization visit (Visit 2) and Visit 4.
5. Diagnosis of VMR/IR to include ALL of the following:
a Two year clinical history of VMR/IR (written or verbal confirmation) and
evidence to support the perennial nature of the disorder and its potential
fluctuation with weather conditions, such as, seasonal changes, abrupt changes
in temperature, weather fronts, and variations in humidity, along with symptoms
provoked by respiratory irritant exposure (e.g., tobacco smoke, perfumes, paint
fumes). VMR/IR chronic symptoms would include rhinorrhea, nasal congestion
and postnasal drip.
b Subjects must have checked at least 3 of the Inhaled/Strong Odor and/or
Weather/Temperature Change Triggers (making their VMR/IR symptoms
worse) included on the Vasomotor/Idiopathic Rhinitis Questionnaire completed
at Visit 1.
c Negative skin tests (by prick method), response to seasonal allergens (including
tree, grass and weed pollens) and perennial allergens (including animal dander,
house dust mites, cockroach and mold) relevant to the geographical area
completed at Visit 1.
A negative response for allergen skin prick testing is defined as a wheal < 3 mm
larger than the diluent control.
d Positive response to a histamine skin test (prick method) completed at Visit 1.
A positive response for histamine skin prick testing is defined as a wheal ≥ 3mm
larger than the diluent control.
e Normal sinus radiograph (Waters view) to rule out sinusitis (presence of
mucosal thickening of ≥ 6 mm at the point of maximal thickening or an air fluid
level or opacification). The sinus radiograph should be scheduled at Visit 1.
f Nasal cytology negative for eosinophils (Rhino-probe smear method). The nasal
cytology sample is collected at Visit 1.
6. Ability to comply with study procedures - Subject understands and is willing, able
and likely to comply with study procedures and restrictions.
7. Literate |
|
| E.4 | Principal exclusion criteria |
Subject will not be eligible for inclusion if any of following criteria apply:
1. Significant concomitant medical conditions, defined as but not limited to:
a Historical/current evidence of clinically significant uncontrolled disease of
any body system. Significant is defined as any disease that, in the opinion of
investigator, would put safety of subject at risk through study
participation or which would confound the interpretation of study results if
disease/condition exacerbated during study.
b severe physical obstruction of the nose/nasal septal perforation that could
affect deposition of double blind intranasal study drug
c nasal/throat injury or surgery in last 3 mths
d asthma, with exception of mild intermittent asthma.
e rhinitis medicamentosa
f bacterial/viral infection of upper respiratory tract within 2 wks of Visit 1 or
during screening period
g documented evidence of acute or significant chronic sinusitis, as determined by
sinus radiograph (Waters view) done at Visit 1
h current or history of glaucoma and/or cataracts or ocular herpes simplex
i physical impairment that would affect subject’s ability to participate in study
j clinical evidence of Candida infection of nose or oropharynx
k history of psychiatric disease, intellectual deficiency, poor motivation, substance
abuse, or other conditions that will limit validity of informed consent or that would
confound interpretation of study results
l history of or current use of cocaine
m history of adrenal insufficiency
n history of shingles
o Subject not eligible if has chickenpox/measles, or has been exposed
during last 3 wks and is non-immune. If a subject develops chickenpox/
measles during study, they will be withdrawn. If a non-immune subject
is exposed during study, their continuation will be at discretion of investigator,
taking into consideration likelihood of developing active disease.
2. Use of corticosteroids, defined as:
• Intranasal corticosteroid within 4 wks prior to Visit 1.
• Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatological
corticosteroid (with exception of hydrocortisone cream/ointment, 1% or less)
within 8 wks prior to Visit 1.
3. Use of other allergy medications within timeframe indicated relative to Visit 1
• Intranasal or ocular cromolyn within 14 days prior to Visit 1
• Short-acting prescription and OTC antihistamines, including ocular preparations
and antihistamines contained in insomnia and ‘nighttime’ pain formulations
taken for insomnia, within 3 days prior to Visit 1
• Long-acting antihistamines within 10 days prior to Visit 1: loratadine,
desloratadine, fexofenadine, cetirizine
• Long-acting antihistamine, astemizole, within 12 wks prior to Visit 1
• Oral or intranasal decongestants within 3 days prior to Visit 1
• Intranasal, oral, or inhaled anticholinergics within 3 days prior to Visit 1
• Oral antileukotrienes within 3 days prior to Visit 1
• Subcutaneous omalizumab within 5 mths of Visit 1
• Intranasal antihistamines within 2 wks prior to Visit 1
• Ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions,
homeopathic preparations, lubricants, sympathomimetic or vasoconstrictor
preparations during screening or treatment periods. No exclusion period
prior to screening (Visit 1) is required for these treatments.
• Throat treatments during screening and treatment periods. No exclusion period
prior to screening (Visit 1) is required for these treatments.
4. Use of other medications that may affect VMR/IR or its symptoms
• Chronic use of concomitant medications that would affect assessment of
effectiveness of study drug
• Chronic use of long-acting beta-agonists
• Chronic use of other intranasally administered medications
5. Chronic use of medications which could cause drug-induced rhinitis including ACE
inhibitors, reserpine, guanethidine, methyldopa, hydralazine, betablockers,
alpha-adrenoceptor antagonists, phentolamine, chlorpromazine, aspirin and non-
steroidal anti-inflammatory medications
6. Use of immunosuppressive medications 8 wks prior to screening and during
study
7. Use of any medications that significantly inhibit the cytochrome P450 subfamily
enzyme CYP3A4
8. Immunotherapy
9. Allergy/Intolerance to corticosteroids or any excipients in product
10. Clinical trial/experimental medication experience - Recent exposure to
investigational study drug within 30 days of Visit 1 or participation in previous or
current GSK GW685698X study
11. Positive or inconclusive pregnancy test at Visit 1 or Visit 2 or female who is
breastfeeding
12. Affiliation with investigational site
13. Subjects who have used smoking products within past year.
14. Findings of a clinically significant, abnormal ECG
15. Findings of a clinically significant laboratory abnormality |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Mean change from baseline over the entire treatment period in daily, reflective total
nasal symptom scores (rTNSS).
The total nasal symptom score (TNSS) is the sum of the 3 individual symptom scores for rhinorrhea, nasal congestion and postnasal drip where each symptom is scored on a scale of 0 to 3. The maximum sum for TNSS is 9. The rTNSS is a rating of the severity of symptoms over the previous 12 hours and is performed in the AM (AM rTNSS) and PM (PM rTNSS). The daily reflective total nasal symptom score (rTNSS) is defined as the average of the AM rTNSS and PM rTNSS assessments. The baseline TNSS is defined as the average of the daily rTNSS over the 4 consecutive 24-hour periods prior to randomization, including the assessment the morning of randomization prior to study drug administration. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| 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
| |
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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