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The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers | Clinical Trials | Clareo Health

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The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers

NCT01530464•Thies Schroeder

View on ClinicalTrials.gov

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 aminophylline and ambrisentan in healthy human subjects. The secondary objective is to assess the pharmacokinetic profiles of theophylline (aminophylline) and ambrisentan 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 aminophylline or ambrisentan alone, followed by a 48 hour wash out interval. Subsequently, Period III consists of the simultaneous administration of both drugs. All subjects are to be confined to the Duke Clinical Research Unit throughout all treatment periods \[Study Day -1 to Study Day 6 (discharge)\]. A sufficient number of healthy adult subjects will be consented in order to enroll 24 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: Aminophylline 500 mg (corresponding to 395 mg theophylline). Treatment 2: Ambrisentan 5 mg. Treatment 3: Aminophylline, 500 mg plus Ambrisentan, 5 mg. After completion of each treatment period, the subjects will proceed to the next period provided no Stopping Rules criteria have been met

Eligibility

Age

18 - 40 years

Sex

ALL

Healthy Volunteers

Yes

Inclusion Criteria

•Subjects must give written informed consent to participation in the study prior to screening. Consent will be documented by the subject's dated signature that will be counter-signed and dated by a witness. The appropriate HIPAA authorization forms must be signed and dated by the subject.
•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 150 lbs. 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 from the time of admission to the clinical research inpatient unit through at least 48 hours following discharge.
•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 either surgically sterile (removal of both ovaries and/ or uterus at least 12 months prior to dosing), or 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
•Male subjects of child-fathering potential must agree to avoid causing 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.

Exclusion Criteria

•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.
•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
+18 more criteria

Locations (1)

Duke Clinical Research Unit

Durham, North Carolina, United States

Key Dates

Start Date

February 1, 2012

Primary Completion Date

April 1, 2012

Completion Date

April 1, 2012

Last Updated

January 16, 2014

Enrollment

ACTUAL participants

Conditions

High Altitude Pulmonary Hypertension

Interventions

Aminophylline

DRUG

Ambrisentan

DRUG

Aminophylline plus ambrisentan

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 16, 2014Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers

Inclusion Criteria

Exclusion Criteria

High Altitude (HA) Residents With High Altitude Pulmonary Hypertension (HAPH), Pulmonary Artery Pressure (PAP) Assessed at HA (3200 m) vs LA (760 m)

HAPH Registry: Time Course and Prognostic Significance of Pulmonary Artery Pressure in Highlanders.

Cerebral Tissue Oxygenation in Highlanders/Lowlanders