Intranasal SB-705498 in Allergic Rhinitis (AR) Patients

NCT01424397 | Completed Phase 2 Results

• 2 other identifiers: 1119242011-000115-11
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rhinitis

Outcome Measures

Primary Outcomes (1)

• Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8

  Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC \[tf-t1 hours\]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS.

  Day 8 of each treatment period

Secondary Outcomes (10)

• Mean TNSS and Its Individual Components From Day 4 to Day 8

  pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period

• Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)

  Day 8

• Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo

  Day 8

• Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8

  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)

• Maximum Observed Concentration (Cmax) for SB-705498 on Day 8

  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)

Study Arms (4)

SB-705498

EXPERIMENTAL

Experimental

Drug: SB-705498

Fluticasone Propionate

ACTIVE COMPARATOR

Active Comparator

Drug: FP

Placebo

PLACEBO COMPARATOR

Placebo Comparator

Drug: placebo

SB-705498+FP

EXPERIMENTAL

Experimental

Drug: SB-705498; Drug: FP

Interventions

SB-705498 DRUG

12mg intranasal

SB-705498; SB-705498+FP

FP DRUG

200ug intranasal

Fluticasone Propionate; SB-705498+FP

placebo DRUG

placebo intranasal

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• TNSS score of \>=4 following screening allergen challenge chamber.
• Positive skin prick test for seasonal pollen
• Positive RAST for seasonal pollen
• Healthy as determined by responsible physician with the exception of mild asthma and AR
• Male or female between 18 and 65 years of age inclusive.
• 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.
• 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.
• Body weight ≥ 50 kg (males) and ≥45kg (females) and BMI within the range 19 - 29.9 kg/m2 (inclusive).
• Screening pre-challenge FEV1 greater than or equal to 80% and baselines FEV1/FVC greater than or equal to 70% of predicted value.
• Capable of giving written informed consent.
• Average QTcB, \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
• AST and ALT \< 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN

You may not qualify if:

• Nasal abnormalities likely to affect the outcome of the study,
• History of frequent nosebleeds.
• Respiratory disease other than mild asthma
• A positive pre-study Hepatitis B or Hepatitis C result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities
• Positive pre-study drug/alcohol/smoking screen.
• A positive test for HIV antibody.
• 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.
• 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.
• Exposure to more than four new chemical entities within 12 months prior to D1.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days prior to the first dose of study medication.
• History of sensitivity to any of the study medications, or components
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Vienna, A-1150, Austria

Location

Related Publications (1)

• 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.

  PMID: 23735181 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Rhinitis

Interventions

SB 705498

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: August 29, 2011
• Study Start: April 14, 2011
• Primary Completion: July 7, 2011
• Study Completion: July 7, 2011
• Last Updated: September 13, 2019
• Results First Posted: September 13, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)