The Effect of Concomitant Administration of Erythromycin and Diltiazem on CYP3A Activity in Healthy Volunteers

NCT00318201 | Completed Phase 4 DMC

• 4 other identifiers: # 0412-09R01GM067308/NIGMSMO1RR000750/GCRC #1267R01GM067308
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

We, the researchers at the Indiana University School of Medicine, are doing this study to better understand how the effects of certain medications are altered when taken simultaneously, or in combination with each other. We will also look at how each volunteer's genes (DNA) may affect the way these medications are metabolized. Hypothesis: We will test the hypothesis that the extent of drug-drug interaction caused by the combination of erythromycin and diltiazem is not predictable from the extent of interaction produced by each inhibitor alone. Specifically we will test the hypothesis that the combination of erythromycin and diltiazem will cause a greater decrease in midazolam intravenous and oral clearance than the sum of the decreases caused by each inhibitor alone.

Conditions

Healthy

Keywords

Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• Primary Aims: To quantify the extent of the drug-drug interaction between erythromycin and midazolam

  2 days

• To quantify the extent of the drug-drug interaction between diltiazem and midazolam

  2 days

• To quantify the extent of the drug-drug interaction between the combination of diltiazem and erythromycin, and midazolam

  2 days

Secondary Outcomes (2)

• Secondary Aims: To quantify the effects of erythromycin, diltiazem, and the combination of erythromycin and diltiazem on the electrocardiogram (EKG) PR interval

  2 days

• To quantify the effects of erythromycin, diltiazem, and the combination of erythromycin and diltiazem on the heart-rate corrected QT interval of the EKG

  2 days

Study Arms (1)

1

EXPERIMENTAL

Altered efficacy for drug to drug interaction of diltiazam with erythromycin

Drug: Erythromycin; Drug: Diltiazem

Interventions

Erythromycin DRUG

1

Diltiazem DRUG

1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Approximately 45 healthy volunteers may be recruited to participate in the study, with a goal of 15 healthy volunteers (7 or 8 males) completing the entire four phases. All potential subjects:
• Must be a non-smoker
• Between 18 to 50 years of age
• Have a body mass index of 30 or less
• Must be willing to undergo a screening physical examination and proven to be free from metabolic, cardiac, pulmonary, renal or hepatic dysfunction as determined by the screening physical, medical history, 12-lead electrocardiography, and laboratory values which include: a CMP (complete metabolic profile), a CBC/diff/plt (complete blood count with differential and platelet count), serum pregnancy test (if applicable), and UA (urinalysis). Also, given the uncertain effects of these drugs on the fetus and the fact that hormonal contraceptives are prohibited, the female subjects should be on two other forms of birth control (e.g. condom, contraceptive foam).

You may not qualify if:

• Potential volunteers will be excluded:
• If they have allergies or are hypersensitive to any of the study medications:
• A. Midazolam (Versed) or related benzodiazepines drugs such as diazepam (Valium) or alprazolam (Xanax).
• B. Diltiazem (Cardizem, Dilacor) or related calcium channel blockers such as verapamil (Calan, Isoptin).
• C. Erythromycin (Erythrocin, E-mycin, Ery-tab) or related antibiotics such as clarithromycin (Biaxin) or have experienced abdominal pain when taking erythromycin or other related medications.
• If they are taking any prescription medication on a regular basis including contraceptives such as oral birth control pills, transdermal patches or injections (Depo-Provera).
• If they are taking over-the-counter medications, any herbal or dietary supplement (including Benadryl, Sudafed, St. John's wort, herbal teas, vitamins and garlic supplements) that cannot be stopped for the study duration. Use of over-the-counter drugs for the treatment of minor, short-lived (2 to 3 days) symptoms may be allowable (such as Tylenol) but must first be approved by a study investigator.
• If they have donated blood within the past two months, or are anemic (have a hemoglobin level less than 12.5 mg/dl).
• If they weigh less than 52 kg, or have a BMI (Body Mass Index) greater than 32.
• If they have a screening or baseline EKG reading that is abnormal or could place them at higher risk as decided by the study doctors (baseline corrected QT interval in the EKG of 450 msec or greater or a baseline PR interval in the EKG of 210 msec or greater).
• If they have a history of bradycardia or consistently have a heart rate less than 55 beats per minutes.
• If they have any history of heart disease or have a family medical history of sudden death (heart stopping suddenly without warning).
• If they have a history of psychiatric problems that may be exacerbated by participation in this study, or if the subject can not state a good understanding of this study's risks and requirements.
• If they have a positive serum pregnancy test during the screening process or have a positive urine pregnancy test (UPT) which will be obtained just prior to each of the four study phases.
• If they are currently breastfeeding.

Sponsors & Collaborators

• Indiana University School of Medicine: lead

Study Sites (1)

Indiana University Medical Center / GCRC

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Interventions

Erythromycin; Diltiazem

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephen D Hall, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 21, 2006
• First Posted: April 26, 2006
• Study Start: April 1, 2006
• Study Completion: December 1, 2007
• Last Updated: April 6, 2012

Record last verified: 2007-12

Locations

US (1)