StahistRx Phase 2, Five-arm, Parallel Group, Active vs Active, Double-blind Study

Study Overview
=================
Brief Summary
-----------------
This active vs active comparative trial will evaluate the safety and efficacy of incremental doses of atropine in combination with pseudoephedrine 120 mg/chlorpheniramine 8 mg in adult patients with a history of seasonal allergic rhinitis. Hypotheses are defined by total nasal symptom scores (TNSS) recorded by subjects in diaries where efficacy will be established by statistical significance where p < 0.05.

Detailed Description
-----------------
Actives in each of the five study arms: Pseudoephedrine 120 mg/Chlorpheniramine 8 mg/Atropine 0.36 mg Pseudoephedrine 120 mg/Chlorpheniramine 8 mg/Atropine 0.24 mg Pseudoephedrine 120 mg/Chlorpheniramine 8 mg/Atropine 0.12 mg Pseudoephedrine 120 mg/Chlorpheniramine 8 mg Atropine 0.24 mg

Official Title
-----------------
A Phase 2, Double-Blind, Parallel-Group, Dose-Ranging Study Evaluating Safety/ Efficacy Atropine Doses With Pseudoephedrine and Chlorpheniramine in SAR Patients 12 Years of Age and Older

Conditions
-----------------
Rhinitis, Seasonal, Allergic

Intervention / Treatment
-----------------
* Drug: PSE 120 mg, CM 8 mg, Atr 0.36 mg
* Drug: PSE 120 mg, CM 8 mg, Atr 0.24 mg
* Drug: PSE 120 mg, CM 8 mg, Atr 0.12 mg
* Drug: PSE 120 mg, CM 8 mg
* Drug: Atropine 0.24 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and females of any ethnic group between 12 and 60 years of age. History of moderate to severe SAR for at least two years; defined as having a score of 2 or more on a 0-3 point scale Documentation of sensitivity will be obtained from medical records or positive skin testing or in vitro specific IgE test. Have a TNSS score of 6 with at least an average of 2.0 in the rhinorrhea sub-score during the placebo-run in phase. Is a non-pregnant, non-lactating female who is postmenopausal, naturally or surgically sterile, or who agree to use effective contraceptive methods throughout the course of the study. If female of childbearing potential, must agree to use listed acceptable birth control methods... If female of childbearing potential, has a negative urine human chorionic gonadotropin (hCG) pregnancy test at screening Is able to swallow whole tablets of orally administered medication Is able to understand and provide signed informed consent Exclusion Criteria: Has asthma requiring corticosteroid treatment Is currently undergoing chronic or intermittent use of inhaled, oral, intramuscular, intravenous, and/or potent or super potent topical corticosteroids Has taken any of the following medications in the indicated time period prior to study enrolment: Intranasal, opthalmic, or systemic corticosteroids (1 month) Intranasal cromolyn (2 weeks) Intranasal or systemic decongestants (3 days) Intranasal or systemic antihistamines (7 days) or leukotriene inhibitors (7 days) Documented evidence of acute or significant chronic sinusitis, as determined by the individual investigator Has a history of allergic reaction to or known sensitivity to the active or inactive ingredients in the investigational products used in this study Chronic use of concomitant medications (e.g., tricyclic antidepressants) that would affect assessment of the effectiveness of the study medication Rhinitis medicamentosa A history of glaucoma Has known or suspected pregnancy, planned pregnancy, or lactation (for female patients) Is currently receiving immunotherapy, unless at stable maintenance dose for at least 1 month. Presence of a medical condition that might interfere with treatment evaluation or require a change in therapy. Plans to travel outside the study area for a substantial portion of the study period Has a history in the last 2 years or current evidence of abuse of illicit drugs, prescription medications, or alcohol that, in the opinion of the Investigator, would interfere with adherence to study requirements. Has exposure to any investigational agent within 30 days prior to study entry. Has clinically significant mental illness (to be determined by the Investigator) Has a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PSE 120 mg, CM 8 mg, Atr 0.36 mg<br>Pseudoephedrine 120 mg,chlorpheniramine 8 mg, atropine 0.36 mg tablet dosed BID for 7.5 days | Drug: PSE 120 mg, CM 8 mg, Atr 0.36 mg<br>* Pseudoephedrine 120 mg, chlorpheniramine 8 mg, atropine 0.36 mg white, scored, tablets with M27 on scored side and plain on the other side<br>* Other names: Pseudoephedrine, chlorpheniramine (Chlor-Trimeton), atropine;|
| Experimental: PSE 120 mg, CM 8 mg, Atr 0.24 mg<br>Pseudoephedrine 120 mg, chlorpheniramine 8 mg, atropine 0.24 mg tablets dosed BID for 7.5 days | Drug: PSE 120 mg, CM 8 mg, Atr 0.24 mg<br>* Pseudoephedrine 120 mg, chlorpheniramine 8 mg, atropine 0.24 mg white, scored, tablets with M27 on scored side and plain on the other side<br>* Other names: Pseudoephedrine, chlorpheniramine (Chlor-Trimeton), atropine;|
| Experimental: PSE 120 mg, CM 8 mg, Atr 0.12 mg<br>Pseudoephedrine 120 mg, chlorpheniramine 8 mg, atropine 0.12 dosed BID for 7.5 days | Drug: PSE 120 mg, CM 8 mg, Atr 0.12 mg<br>* Pseudoephedrine 120 mg, chlorpheniramine 8 mg, atropine 0.12 mg white, scored, tablets with M27 on scored side and plain on the other side<br>* Other names: Pseudoephedrine, chlorpheniramine (Chlor-Trimeton), atropine;|
| Active Comparator: PSE 120 mg, CM 8 mg<br>Pseudoephedrine 120 mg, chlorpheniramine 8 mg white, scored, tablets with M27 on scored side and plain on the other side | Drug: PSE 120 mg, CM 8 mg<br>* Pseudoephedrine 120 mg, chlorpheniramine 8 mg tablets dosed BID<br>* Other names: Pseudoephedrine, chlorpheniramine (Chlor-Trimeton);|
| Experimental: Atropine 0.24 mg<br>Atropine 0.24 mg tablets dosed BID for 7.5 days | Drug: Atropine 0.24 mg<br>* Atropine sulfate 0.24 mg white, scored, tablets with M27 on scored side and plain on the other side<br>* Other names: atropine sulfate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-ranging data for atropin | To provide dose-ranging data for atropine and select a dose of Atropine for Phase 3 clinical development using Total Nasal Symptom Score (TNSS) as the primary endpoint plus recording of adverse events | 7.5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish effect size for determining power and TNSS efficacy endpoint | To establish an effect size of a Pseudoephedrine 120 mg/Chlorpheniramine 8 mg/Atropine combination versus Pseudoephedrine 120 mg/Chlorpheniramine 8 mg to statistically power the pivotal phase of the study using TNSS as the primary endpoint | 7.5 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rhinitis, seasonal, allergic