Table 2. Select Clinical Trials in Healthy Volunteers
| Study | N | Antiemetic treatments | Electrocardiogram assessments | Electrocardiographic effects |
|---|---|---|---|---|
| Hunt 1995 Randomized, double-blind, placebo-controlled dose-ranging (single-dose) |
80 | D:0.6-, 0.8-, 1-,
1.25-, 1.5-, 1.75-, 2-, 2.25-, 2.5-, 2.75-, 3-, 3.5-, 4-; 4.5-, and 5-mg/kg IV over 10 min Placebo |
Prior
to antiemetic therapy (baseline), at 1-2 h after antiemetic, and at end
of evaluation period (48 or 72 h) |
1. Reversible changes
in PR and QRS complex durations. 2. Patients were asymptomatic. 3. None of the QTc interval measurements were > 420 msec, even at the highest dose. |
| Benedict
1996 Randomized, placebo-controlled, single-blind, 5-way crossover |
30 | D:1.2-, 1.8-, or 2.4-mg/kg
IV over 15 min O: 32 mg IV over 15 minutes Placebo |
Prior to antiemetic therapy (baseline), and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h after antiemetic | 1. Acute, transient,
and asymptomatic ECG interval changes with D and O. 2. None of the QTc interval measurements were >420 msec, even at the highest dose. 3. Increases in QT and QTc intervals were statistically significant, but not considered clinically significant 4. All changes returned to baseline by 8 h. |
| Boike
1997 Randomized, double-blind, double-dummy, 4-period, crossover |
13 | G:
10 mcg/kg IV over either 30 sec or 5 min O: 32 mg IV Placebo |
Prior to antiemetic therapy, after infusion, and at intervals up to 24 hours after the third injection | 1. O,G, and placebo
all prolonged QTc interval without demonstrable clinical effects, although
QTc interval was significantly prolonged with O versus G or placebo. 2. No significant differences between O, G, or placebo in other ECG intervals, although all were slightly prolonged. 3. No prolongation of any ECG interval was clinically meaningful. |
| Upward
1990 Single-blind, placebo- controlled, dose-escalation crossover |
8 | G:
2.5-300 mcg/kg IV over 30 min G: 40-160 mcg/kg IV over 3 min Placebo |
Prior to antiemetic therapy (baseline) and at end of infusion | 1. Only results for
the 300 mcg/kg dose were reported. 2. No clinically significant changes in pulse, blood pressure, or ECG intervals during or after antiemetic admininstration. |