Safety Evaluation of Aminophylline and Methazolamide

Study Overview
=================
Brief Summary
-----------------
This safety study is the first in a series of studies testing the application of the combination of aminophylline and methazolamide.

Detailed Description
-----------------
After successful completion of this safety trial, our goal will be to evaluate the safety of this combination in healthy individuals exposed to hypoxia and exercise. Subsequently, an efficacy study will clarify whether this drug combination improves physical and mental functions in human subjects under high altitude conditions.

Official Title
-----------------
The Safety Evaluation of Aminophylline and Methazolamide When Administered Orally Alone and in Combination to Healthy Volunteers

Conditions
-----------------
Mountain Sickness

Intervention / Treatment
-----------------
* Drug: Aminophylline
* Drug: Methazolamide
* Drug: Aminophylline and Methazolamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be healthy non-smoking adult male and female volunteers between the ages of 18 and 40 years, with a BMI of 18-30 kg/m2 and weighting at least 150 lbs. Women who are of childbearing potential, must, if sexually active, must agree to use appropriate contraceptive measures for the duration of the study and for one (1) month afterwards. Subjects must agree not to donate blood, plasma, platelets, or any other blood components during the study and for 4 weeks after the last dose. Exclusion Criteria: History or manifestation of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematologic or other medical disorders. Serious mental or physical illness within the past year. History of clinically significant illness within 4 weeks prior to Day 1. History of allergic reaction, hypersensitivity or idiosyncratic reaction to any of the products administered during the study, including allergy to any sulfa or sulfonamide derivatives. Use of any of the following: Any concomitant medication. Subjects who have received any prescribed or non-prescribed (over-the-counter [OTC]) systemic medication, topical medications, or herbal supplements within 14 days from Day 1. St. John's Wort (hypericin) must not have been taken for at least 30 days prior to Period 1, Day 1. Any drugs, foods or substances known to be strong inhibitors or strong inducers of CYP enzymes (also known as cytochrome P450 enzymes); especially CYP 1A2, or Pgp within 30 days prior to Period 1, Day 1. Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years. Positive results on screening tests for drugs of abuse, cotinine or alcohol at screening or the pre-dose assessment at check-in. Clinically significant ECG abnormality, in the opinion of the Investigator. Use of tobacco products or other nicotine-containing products (including smoking cessation aids, such as gums or patches) with in 14 days of screening and throughout hospitalization. Subjects of childbearing potential who are pregnant (as based on test results) or are breast feeding. Has taken any other investigational drug during the 30 days prior to the screening visit or is currently participating in another investigational clinical trial. Subjects who have made any significant donation (including plasma) or have had a significant loss of blood within 30 days prior to Period 1, Day 1. Receipt of a transfusion or any blood products within 30 days prior to Period 1, Day 1.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sequence A<br>Aminophylline, Methazolamide, Aminophylline and Methazolamide | Drug: Aminophylline<br>* Aminophylline dosage form-tablet dosage-500mg<br>* Other names: theophylline;Drug: Methazolamide<br>* Methazolamide dosage form-tablet dosage-250mg<br>* Other names: Neptazane;Drug: Aminophylline and Methazolamide<br>* Aminophylline 500mg orally and Methazolamide 250mg orally<br>* Other names: Neptazane;|
| Active Comparator: Sequence B<br>Methazolamide, Aminophylline, Aminophylline and Mathazolamide | Drug: Aminophylline<br>* Aminophylline dosage form-tablet dosage-500mg<br>* Other names: theophylline;Drug: Methazolamide<br>* Methazolamide dosage form-tablet dosage-250mg<br>* Other names: Neptazane;Drug: Aminophylline and Methazolamide<br>* Aminophylline 500mg orally and Methazolamide 250mg orally<br>* Other names: Neptazane;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events. | Adverse event data was evaluated for incidence and severity for 6 days. | 6 days. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Altitude Sickness, High Altitude Sickness