Mountain Sickness
Conditions
Keywords
Altitude Sickness, High Altitude Sickness
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.
Interventions
DRUGAminophylline
Aminophylline dosage form-tablet dosage-500mg
DRUGMethazolamide
Methazolamide dosage form-tablet dosage-250mg
DRUGAminophylline and Methazolamide
Aminophylline 500mg orally and Methazolamide 250mg orally
Sponsors
Defense Advanced Research Projects Agency
University of Colorado, Denver
Poudre Valley Health System
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events. | 6 days. | Adverse event data was evaluated for incidence and severity for 6 days. |
Countries
United States
Participant flow
Recruitment details
The study proposed to randomize approximately 24 subjects to complete 16.
Pre-assignment details
A total of 26 subjects were screened and consented. Of the subjects assessed, 21 (81%) passed and 5 (19%) were screen failures. Of those subjects who were screen failures, 3 (60%) had abnormal lab results and 2 (40%) had scheduling difficulties.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A Treatment 1, Treatment 2, Treatment 3
Treatment 1 : Aminophylline dosage form-tablet dosage-500mg
Treatment 3 : Aminophylline 500mg orally and Methazolamide 250mg orally | 8 |
| Sequence B Treatment 2, Treatment 1, Treatment 3
Treatment 3 : Aminophylline 500mg orally and Methazolamide 250mg orally
Treatment 2 : Methazolamide dosage form-tablet dosage-250mg | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Sequence A | Sequence B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Continuous | 25.60429 years STANDARD_DEVIATION 5.12602 | 25 years STANDARD_DEVIATION 3.16228 | 25.125 years STANDARD_DEVIATION 3.96443 |
| BMI = <=18-30 kg/m2 | 8 Participants | 8 Participants | 16 Participants |
| Gender Female | 6 Participants | 2 Participants | 8 Participants |
| Gender Male | 2 Participants | 6 Participants | 8 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 16 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Adverse Events.
Adverse event data was evaluated for incidence and severity for 6 days.
Time frame: 6 days.
Population: All enrolled participants were analyzed for adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A | Adverse Events. | 29 Events |
| Sequence B | Adverse Events. | 40 Events |