High Altitude Pulmonary HypertensionPhase 1NCT01566565
The Safety Evaluation of Drug Combinations Against High Altitude Pulmonary Hypertension
A Phase 1 study testing Theophylline and Bambuterol in people with High Altitude Pulmonary Hypertension, run by Norwegian Armed Forces Medical Service at 1 site in Norway.
Trial summary
This is a Phase I, three period, two sequence, open-label, randomized, crossover study, with the primary objective of testing the safety and tolerability of combined oral doses of theophylline and bambuterol in healthy human subjects. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- High Altitude Pulmonary Hypertension
- What is being tested?
- Theophylline and Bambuterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNorway
- Study dates
- Mar 2012to May 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must give written informed consent to participation in the study prior to screening. Consent will be documented by the subject's dated signature
- 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 weighing at least 68 kg. Subjects health status will be determined by the medical history, physical examination, vital signs, electrocardiogram, blood chemistry, hematology, and urinalysis performed at screening.
- Subjects must be willing to fast a minimum of 8 hours prior to screening.
- Subjects must be willing to abstain from alcohol and xanthine-containing food and beverages (in example coffee, tea, and colas) from 48 hours before the time of admission to the clinical research inpatient unit and until last PK sample of drug given on day 1, 7 and 14 is drawn after 24 hours.
- Subjects must be willing to remain in the clinical research unit continuously for the inpatient portion of the study from admission to discharge.
- Women who are of non-childbearing potential, must be:
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- Surgically sterile (removal of both ovaries and/ or uterus at least 12 months prior to dosing)
- Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing on Day -1, with an FSH level at screening of ≥ 40 mIU/mL.
- Women of child-bearing potential must have a negative serum pregnancy test within 48 hours of receiving study drug and must agree to avoid pregnancy during study and for one month after the last dose of study drug.
- Female subjects of child-bearing potential must agree to avoid pregnancy during study and for three months after the last dose of study drug.
- 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.
- Male subjects must agree not to donate sperm during the study and for 12 weeks after the last dose.
Who cannot join
- Individuals meeting ANY ONE of the following criteria will be excluded from the study:
- Subjects with laboratory results outside the normal range, if considered clinically significant by the Investigator. In addition, subjects must have a normal hematocrit and hemoglobin concentration and be ≥ 36% and ≥ 12.0 g/dL, respectively and plasma potassium concentration of at least 3.9 mmol/l.
- A mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years.
- Unwillingness or lack of ability to comply with the protocol, or to reside in the inpatient unit during the required time period, or to cooperate fully with the Principle Investigator and site personnel.
- Use of any of the following:
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- Any concomitant medication including oral contraceptive hormones. 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.
- Clinically significant ECG abnormality in the opinion of the Investigator.
- Vital signs or clinically significant laboratory values at the screening visit that in the opinion of the Investigator would make the subject an inappropriate candidate for the study.
- Has taken any other investigational drug during the 30 days prior to the screening visit or is currently participating in another investigational clinical trial.
- Made any significant donation (including plasma) or have had a significant loss of blood within 30 or 90 days prior to Period 1, Day 1.
- History or manifestation of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematologic or other medical disorders.
- Subjects who are carriers of the Hepatitis B surface antigen (HbsAg), Hepatitis C antibody, or HIV antibody.
- Serious mental or physical illness within the past year.
- Male subjects who consume more than 28 units of alcohol per week and female subjects who consume more than 21 units of alcohol per week (one unit of alcohol equals 250 mL of beer, 100 mL or a medium glass of wine, or 25 mL of spirits) or those subjects who have a significant history of alcoholism or drug/ chemical abuse within the last 2 years.
- Failure to agree to abstain from alcohol, cola, tea, coffee, chocolate and other caffeinated drink/ food from 2 days before each dosing and throughout confinement.
- Positive results on screening tests for drugs of abuse, cotinine or alcohol at screening or the pre-dose assessment at check-in.
- Subjects who have used tobacco products or nicotine-containing products (including smoking cessation aids, such as gums or patches) within 12 months prior to Period 1, Day 1.
- Women of childbearing potential who are pregnant (as based on test results) or are breast feeding.
- Subjects who have a history of hypersensitivity or idiosyncratic reaction to any of the products administered during the study.
- Subjects who, in the opinion of the Investigator, should not participate in the study.
- Subjects who have a history of unexplained syncope; i.e., autonomic dysfunction.
- Subjects who have a history of hypotension, including orthostatic hypotension.
- Lack of ability to understand verbal and/ or written Norwegian.
- History of severe hypersensitivity or allergic reaction to study medication.
- Failure to agree to abstain from grapefruit and grapefruit juice as well as oranges and orange juice from 10 days before the first dose and throughout the study.
- History of clinically significant illness within 4 weeks prior to Day 1.
- Receipt of a transfusion or any blood products within 90 days prior to Period 1, Day 1.
- History of participation in another investigational study or who have participated in an investigational study within the past 30 days prior to Period 1, Day 1.
Trial locations and contacts
1 site in 1 country.
Norway1 site
Institute of Aviation Medicine, Norwegian Armed Forces Medica
Oslo, 0313
About this study
Official title: The Safety Evaluation of Theophylline and Bambuterol When Administered Orally Alone and in Combination to Healthy Volunteers
This is a Phase I, three period, two sequence, open-label, randomized, crossover study, with the primary objective of testing the safety and tolerability of combined oral doses of theophylline and bambuterol in healthy human subjects. The secondary objective is to assess the pharmacokinetic profiles of theophylline and bambuterol when administered alone or in combination. It is hypothesized that the combination of these drugs is generally safe, and that no drug interaction can be observed.
Read the detailed description
This is a Phase I, three period, two sequence, single-center, open-label, randomized, crossover study design. Periods I and II consist of the oral administration of either a single dose of theophylline or bambuterol alone, followed by a 7 day wash out interval. Subsequently, Period III consists of the simultaneous administration of both drugs. All subjects are to be confined to the Oslo University Hospital Research Unit throughout all treatment periods [Study Day 1, 7 and 14]. A sufficient number of healthy adult subjects will be consented in order to enroll 20 and complete 16 subjects who complete all three periods. Replacement of subjects is permitted, if necessary.
Qualified subjects will be randomized into one of two sequences consisting of three Periods as indicated below:
-------------Period 1-----Period 2-----Period 3
Sequence A: Treatment 1 Treatment 2 Treatment 3
Sequence B: Treatment 2 Treatment 1 Treatment 3
TREATMENTS:
Treatment 1: Theophylline 300 mg.
Treatment 2: Bambuterol 20 mg.
Treatment 3: Theophylline 300 mg plus Bambuterol 20 mg.
After completion of each treatment period, the subjects will proceed to the next period provided no Stopping Rules criteria have been met
- Conditions
- High Altitude Pulmonary Hypertension
- Being tested
- Theophylline and Bambuterol
- Medical subject headings
- Pulmonary edema of mountaineers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theophylline and BambuterolDrug
Treatment 3: Theophylline, 300 mg plus Bambuterol, 20 mg
| Study group | Role | What they receive |
|---|---|---|
| Theophylline | Active comparator | Not described Receives: Drug: Theophylline and Bambuterol |
| Bambuterol | Active comparator | Not described Receives: Drug: Theophylline and Bambuterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
To assess the Number of Participants with Adverse Events after dosing, as a Measure of Safety and Tolerability
Measured: 24 hours after dosing
Pharmacokinetic
To assess the pharmacokinetic profiles of theophylline and bambuterol when administered alone or in combination.
PK sample collections for plasma Theophylline and Bambuterol determinations at 0-hour (pre-dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post dose
Measured: 24 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Altitude Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norwegian Armed Forces Medical Service
- Sponsor type
- Other government
- Collaborators
- Duke University, Oslo University Hospital
- Responsible party
- Principal investigator, Trond-Eirik Strand, Norwegian Armed Forces Medical Service
- Investigators
- Trond-Eirik Strand, M.D., Ph.D., Principal investigator, Institute of Aviation Medicine, Norwegian Armed Forces MedicalThies Schroeder, Ph.D., Study director, Department of Radiation Oncology, Duke University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01566565
- Sponsor's protocol ID
- 1-Strand
- Status last verified
- Feb 2013
- First submitted
- 27 Mar 2012
- Last updated
- 26 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety Evaluation of Theophylline and Bambuterol When Administered Orally Alone and in Combination to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01566565
- Acronym / sponsor ID
- 1-Strand
- Conditions
- High Altitude Pulmonary Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Norwegian Armed Forces Medical ServiceOther government
- Collaborators
- Duke University, Oslo University Hospital
- Study start
- Mar 2012
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 29 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, three period, two sequence, open-label, randomized, crossover study, with the primary objective of testing the safety and tolerability of combined oral doses of theophylline and bambuterol in healthy human subjects. The secondary objective is to assess the pharmacokinetic profiles of theophylline and bambuterol when administered alone or in combination. It is hypothesized that the combination of these drugs is generally safe, and that no drug interaction can be observed.
Detailed description
This is a Phase I, three period, two sequence, single-center, open-label, randomized, crossover study design. Periods I and II consist of the oral administration of either a single dose of theophylline or bambuterol alone, followed by a 7 day wash out interval. Subsequently, Period III consists of the simultaneous administration of both drugs. All subjects are to be confined to the Oslo University Hospital Research Unit throughout all treatment periods [Study Day 1, 7 and 14]. A sufficient number of healthy adult subjects will be consented in order to enroll 20 and complete 16 subjects who complete all three periods. Replacement of subjects is permitted, if necessary.
Qualified subjects will be randomized into one of two sequences consisting of three Periods as indicated below:
-------------Period 1-----Period 2-----Period 3
Sequence A: Treatment 1 Treatment 2 Treatment 3
Sequence B: Treatment 2 Treatment 1 Treatment 3
TREATMENTS:
Treatment 1: Theophylline 300 mg.
Treatment 2: Bambuterol 20 mg.
Treatment 3: Theophylline 300 mg plus Bambuterol 20 mg.
After completion of each treatment period, the subjects will proceed to the next period provided no Stopping Rules criteria have been met
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Theophylline | Active comparator | Drug: Theophylline and Bambuterol |
| Bambuterol | Active comparator | Drug: Theophylline and Bambuterol |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Subjects must give written informed consent to participation in the study prior to screening. Consent will be documented by the subject's dated signature
- 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 weighing at least 68 kg. Subjects health status will be determined by the medical history, physical examination, vital signs, electrocardiogram, blood chemistry, hematology, and urinalysis performed at screening.
- Subjects must be willing to fast a minimum of 8 hours prior to screening.
- Subjects must be willing to abstain from alcohol and xanthine-containing food and beverages (in example coffee, tea, and colas) from 48 hours before the time of admission to the clinical research inpatient unit and until last PK sample of drug given on day 1, 7 and 14 is drawn after 24 hours.
- Subjects must be willing to remain in the clinical research unit continuously for the inpatient portion of the study from admission to discharge.
Key exclusion criteria (30 listed)
- Subjects with laboratory results outside the normal range, if considered clinically significant by the Investigator. In addition, subjects must have a normal hematocrit and hemoglobin concentration and be ≥ 36% and ≥ 12.0 g/dL, respectively and plasma potassium concentration of at least 3.9 mmol/l.
- A mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years.
- Unwillingness or lack of ability to comply with the protocol, or to reside in the inpatient unit during the required time period, or to cooperate fully with the Principle Investigator and site personnel.
- Use of any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Theophylline and BambuterolTreatment 3: Theophylline, 300 mg plus Bambuterol, 20 mg | Drug | Bambuterol, Theophylline |
Primary outcome
Adverse Events
Time frame: 24 hours after dosing
To assess the Number of Participants with Adverse Events after dosing, as a Measure of Safety and Tolerability
Pharmacokinetic
Time frame: 24 hours after dosing
To assess the pharmacokinetic profiles of theophylline and bambuterol when administered alone or in combination. PK sample collections for plasma Theophylline and Bambuterol determinations at 0-hour (pre-dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Trond-Eirik Strand, M.D., Ph.D. principal investigator
Institute of Aviation Medicine, Norwegian Armed Forces Medical
Thies Schroeder, Ph.D. study director
Department of Radiation Oncology, Duke University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Theophylline and Bambuterol in people with High Altitude Pulmonary Hypertension, run by Norwegian Armed Forces Medical Service at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 24 hours after dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2013.