The Safety Evaluation of Drug Combinations Against High Altitude Pulmonary Hypertension

NCT01566565 | Completed Phase 1 DMC

• 1 other identifier: 1-Strand
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

High Altitude Pulmonary Hypertension

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  To assess the Number of Participants with Adverse Events after dosing, as a Measure of Safety and Tolerability

  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

  24 hours after dosing

Study Arms (2)

Theophylline

ACTIVE COMPARATOR

Drug: Theophylline and Bambuterol

Bambuterol

ACTIVE COMPARATOR

Drug: Theophylline and Bambuterol

Interventions

Theophylline and Bambuterol DRUG

Treatment 3: Theophylline, 300 mg plus Bambuterol, 20 mg

Bambuterol; Theophylline

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Norwegian Armed Forces Medical Service: lead
• Duke University: collaborator
• Oslo University Hospital: collaborator

Study Sites (1)

Institute of Aviation Medicine, Norwegian Armed Forces Medica

Oslo, 0313, Norway

Location

MeSH Terms

Conditions

Pulmonary edema of mountaineers

Interventions

Theophylline; bambuterol

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Trond-Eirik Strand, M.D., Ph.D.

  Institute of Aviation Medicine, Norwegian Armed Forces Medical

  PRINCIPAL INVESTIGATOR

• Thies Schroeder, Ph.D.

  Department of Radiation Oncology, Duke University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Director General

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: March 29, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: February 26, 2013

Record last verified: 2013-02

Locations

NO (1)