Clinical trial NCT01424397: Intranasal SB-705498 in Allergic Rhinitis (AR) Patients
Official title: A Randomized, Double-blind, Placebo Controlled, Incomplete Block, 3 Way Cross Over Study in Subjects With Allergic Rhinitis to Assess the Effect of Intranasal Repeat Doses of SB-705498 When Administered Alone or in Conjunction With Intranasal Fluticasone Propionate on the Symptoms of Rhinitis in the Vienna Allergen Challenge Chamber
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rhinitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is designed to look at the affect of SB-705498 on allergic rhinitis symptoms induced by an allergen chamber challenge.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of AR, as determined by the presence of rhinitis symptoms that last for several months per year, for more than 1 year and are not attributed to allergy, infections or nasal abnormalities.
2. TNSS score of \>=4 following screening allergen challenge chamber.
3. Positive skin prick test for seasonal pollen
4. Positive RAST for seasonal pollen
5. Healthy as determined by responsible physician with the exception of mild asthma and AR
6. Male or female between 18 and 65 years of age inclusive.
7. A female subject is eligible to participate if she is of:

   * Non-childbearing potential defined as pre-menopausal females with a \\documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<147 pmol/L) is confirmatory\].
   * Child-bearing potential and agrees to use one of the contraception methods listed as instructed. Female subjects must agree to use contraception until 84 days post-last treatment administration.
8. Male subjects with female partners of child-bearing potential must agree to use one contraception as instructed. This must be followed from the time of the first dose of study medication until 84 days post-last treatment administration.
9. Body weight ≥ 50 kg (males) and ≥45kg (females) and BMI within the range 19 - 29.9 kg/m2 (inclusive).
10. Screening pre-challenge FEV1 greater than or equal to 80% and baselines FEV1/FVC greater than or equal to 70% of predicted value.
11. Capable of giving written informed consent.
12. Average QTcB, \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
13. AST and ALT \< 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN

Exclusion Criteria:

1. Nasal abnormalities likely to affect the outcome of the study,
2. History of frequent nosebleeds.
3. Respiratory disease other than mild asthma
4. A positive pre-study Hepatitis B or Hepatitis C result within 3 months of screening
5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities
6. Positive pre-study drug/alcohol/smoking screen.
7. A positive test for HIV antibody.
8. History of regular alcohol consumption within 6 months of the study defined as:

   • An average weekly intake of \>14 drinks for males or \>7 drinks for females.
9. The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product prior to D1.
10. Exposure to more than four new chemical entities within 12 months prior to D1.
11. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days prior to the first dose of study medication.
12. History of sensitivity to any of the study medications, or components
13. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
14. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
15. Lactating females.
16. Subject is mentally or legally incapacitated.
17. Urine cotinine levels indicative of smoking

Primary outcomes:
measure: Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8
timeFrame: Day 8 of each treatment period
Secondary outcomes:
measure: Mean TNSS and Its Individual Components From Day 4 to Day 8
timeFrame: pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period
measure: Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)
timeFrame: Day 8
measure: Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo
timeFrame: Day 8
measure: Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8
timeFrame: Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)
measure: Maximum Observed Concentration (Cmax) for SB-705498 on Day 8
timeFrame: Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)
measure: Number of Participants With Vital Signs of Potential Clinical Importance (PCI)
timeFrame: Up to Week 16
measure: Change From Baseline in ECG Values: Heart Rate
timeFrame: Baseline and Day 8 of each treatment period
measure: Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF
timeFrame: Baseline and Day 8 of each treatment period
measure: Number of Participants With Hematology Parameters of PCI
timeFrame: Up to Week 16
measure: Number of Participants With Clinical Biochemistry Parameters of PCI
timeFrame: Up to Week 16
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bareille P, Murdoch RD, Denyer J, Bentley J, Smart K, Yarnall K, Zieglmayer P, Zieglmayer R, Lemell P, Horak F. The effects of a TRPV1 antagonist, SB-705498, in the treatment of seasonal allergic rhinitis. Int J Clin Pharmacol Ther. 2013 Jul;51(7):576-84. doi: 10.5414/CP201890.