Intranasal SB-705498 in Allergic Rhinitis (AR) Patients

Rhinitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01424397
• Other study ID #: 111924
• Secondary ID: 2011-000115-11
• Status: Completed
• Phase: Phase 2
• Start date: April 14, 2011
• Est. completion date: July 7, 2011

Study information

• Verified date: August 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 7, 2011
• Est. primary completion date: July 7, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• SB-705498
12mg intranasal
• FP
200ug intranasal
• placebo
placebo intranasal

Locations

Country	Name	City	State
Austria	GSK Investigational Site	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Austria, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean TNSS and Its Individual Components From Day 4 to 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. Mean of TNSS and its individual components is presented pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on 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
Secondary	Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)	Total Nasal Airflow is calculated as the sum of the left nostril and the right nostril airflow values. AAR is a very sensitive method of assessing clinical parameters of nasal obstruction (nasal flow, nasal resistance and nasal flow increase). A participant was instructed to breathe through one nostril while a sensor in the other nostril measured the difference in pre-nasal and choanal pressure. The system was connected to a computer. Nasal flow and nasal resistance were observed at pressure levels of 75, 150 and 300 Pascal. The defined measuring range for the flow was +-1000 milliliter per second (mL/s). Weighted means for total nasal airflow Resistance was calculated by dividing the area under the curve between 1 and 4 hours (via the linear trapezoidal method) by the total duration that the participant took to complete the chamber challenge assessments.	Day 8
Secondary	Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo	The RQLQ composed of 28 items covering 7 domains of health. Each question is scored on a scale of 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). 7 domains were: Activities (3 items):1, 2, 3;Sleep (3 items): 4, 5, 6; Non-nose/eye symptoms (7 items): 7, 8, 9, 10, 11, 12, 13; Practical Problems (3 items): 14, 15, 16; Nasal Symptoms (4 items): 17, 18, 19, 20; Eye Symptoms (4 items): 21, 22, 23, 24; Emotional (4 items): 25, 26, 27, 28 consisted of total 28 items. Domain activity score = total post-baseline score for individualized activity items answered on both visits divided by total Baseline score for individualized activity items answered on both visits multiplied by the Baseline score for item(s) missing post-baseline. The global RQLQ score was calculated by averaging all 28 item scores, which ranges from 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). Higher scores indicate worsening of symptoms.	Day 8
Secondary	Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8	Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. Values were reported as Least Squares Geometric Means with respective % CV.	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)
Secondary	Maximum Observed Concentration (Cmax) for SB-705498 on Day 8	Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as least squares geometric means with respective geometric coefficient of variation (% CV).	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)
Secondary	Number of Participants With Vital Signs of Potential Clinical Importance (PCI)	Vital signs assessment included heart rate, blood pressure, and temperature. Criteria for vital sign values meeting potential clinical concern included: systolic blood pressure (SBP) <85 and >160 millimeters of mercury (mm Hg), diastolic blood pressure (DBP) < 45 and > 100 mm Hg, temperature <36 and >37.5 Degree Celsius and heart Rate <40 and >110 beats per minute. Only parameters with PCI values are reported.	Up to Week 16
Secondary	Change From Baseline in ECG Values: Heart Rate	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, and QTc intervals. Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.	Baseline and Day 8 of each treatment period
Secondary	Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF). Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.	Baseline and Day 8 of each treatment period
Secondary	Number of Participants With Hematology Parameters of PCI	The PCC range for hematology parameters included white blood cell count, low: 0.67, high 1.82, neutrophil count, low: 0.83, Hemoglobin, male- high 1.03, female- high 1.13, hematocrit, male- high 1.02, female- high 1.17, Platelet Count, low: 0.67, high: 1.57, lymphocytes, low 0.81. Only parameters with PCI values are reported.	Up to Week 16
Secondary	Number of Participants With Clinical Biochemistry Parameters of PCI	The PCC range for clinical chemistry parameters included albumin, low: 0.86, millimole per liter (mmol)/L, calcium, low: 0.91, high: 1.06, glucose. Low: 0.71, high: 1.41, Potassium, low: 0.86, high: 1.10, Sodium, low: 0.96, high: 1.03, Total CO2, Low: 0.86, high: 1.14, Creatinine, in male, Low: <75 micromole per liter (µmol/L), high: >110 µmol/L, female, Low: <65 µmol/L, high: >95, Blood Urea Nitrogen (BUN), high: >1.5xULN mmol/L, Uric Acid, in male, Low: < 180 µmol/L, high: > 480 µmol/L, female, Low: < 120 µmol/L, high: > 420. Only parameters with PCI values are reported.	Up to Week 16

External 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.