# Presentation: 751415

## Prospective controlled study of QTc prolongation by droperidol in healthy volunteers

- Anesthetic & Life Support Drugs Advisory Committee Meeting
- November 18, 2003
- Mehul Desai, M.D.
- Medical Officer
- Division of Cardiovascular and Renal Drugs

**Center for Drug Evaluation and Research**** **

## Study Objective

- To determine the effect of 0.625, 2.5, 5 mg bolus doses of intravenous droperidol, relative to placebo, on the heart rate corrected QT interval in young, healthy volunteers.

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Study Design

- 4 period, placebo controlled, blinded, randomized, crossover study of 20 healthy volunteers
- 0.625 mg, 2.5 mg, 5 mg, and placebo (IV bolus over 30 seconds)
- Healthy subjects between ages 19-40 years on no prescription or over the counter medications; Normal baseline electrocardiograms.

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Study Methods

- ECG’s:  Baseline, 1, 2, 3, 4, 5, 8, 10, 15, 20, 40, 60, 120, 240, 480, and 720 minutes post dose.
- Read blinded to time, treatment, and subject identity.
- Originally the QT and RR intervals were measured manually in conjunction with a digitizer board. Heart rate was corrected using Fridericia’s method.
- Subsequently, the ECG’s were re-analyzed using digital technology and a subject specific heart rate correction.  In addition, the impact of heart rate trending was also considered. (Dr. Malik)

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results: Subject characteristics

|  | Age (years) | Gender | Ethnicity | Placebo | 0.625 mg | 2.5 mg | 5 mg |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 30 | M | AA | X | X | X | X |
| 2 | 39 | F | A | X | X | X | X |
| 3 | 33 | M | C | X |  | X |  |
| 4 | 35 | F | C |  |  |  | X |
| 5 | 19 | F | AA | X | X | X |  |
| 6 | 23 | M | C | X | X | X |  |
| 7 | 25 | F | C |  | X | X |  |
| 8 | 25 | F | AA | X |  | X |  |

- A = Asian, AA = African American, C = Caucasian, F = Female, M = Male

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results(Adverse Events)

- Neuropsychiatric adverse events lead to early study termination
- Restlessness, anxiety, difficulty concentrating, claustrophobia, etc.
- One subject was unable to work the day following the study due to persistent symptoms

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results: Heart rate

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results: Individually corrected QTc

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results: Average changes in individual QTc 10 – 60 minutes post dose

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Results: Maximal changes in individual QTc

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Conclusions

- This study was underpowered secondary to early termination
- There is a strong suggestion that relatively low doses of droperidol prolong the QTc interval.

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**

## Acknowledgements

- Indiana University:
- Adegboyega A, Gorski JC, Hall SD, Hilligoss J, Pinto A
- FDA:
- Collins JM, Jenkins JK, Honig PK, Haidar S, Huang SM, Hung HMJ, Kweder SL, Lee IP, Lesko LJ, Machado SG, Malinowski H, McCormick C, Pollock M, Sevka M, Temple R, Throckmorton DC
- St. Georges Hospital Medical School, London, UK:
- Malik M

**Anesthetics  and Life Support Drugs Advisory Committee  **
**November 18 and 19, 2003**