Objective: To assess the cardiac safety of a single supratherapeutic dose of carbidopa in healthy adults.

Background: Carbidopa has been approved for use in combination with levodopa for the treatment of Parkinson’s disease for more than 45 years. While the current dose is typically limited to 200 mg daily in divided doses, numerous clinical trials have documented the safety of carbidopa doses of up to 600 mg daily.

Method: Thirty-five healthy adult subjects were randomized to receive single doses of carbidopa 400 mg (blinded), placebo (blinded) or moxifloxacin 400 mg (positive control, unblinded), under fasted conditions, with a minimum 5-day washout between treatments, in a crossover study.  Multiple blood samples and ECG measurements were taken to correlate plasma concentration with potential QTc changes.  The primary endpoint was change from baseline in QTc.

Results: For carbidopa, mean C_max was 1400 ng/mL, median T_max was 3.0 hours and mean half-life was 2.0 hours. There were no clinically significant effects on heart rate, the PR interval, or QRS duration in the carbidopa group.  No subject developed new, clinically significant ECG morphologic findings. Assay sensitivity was successfully demonstrated, and in the by timepoint analysis, the 90% upper confidence bound for placebo-corrected QTc change from baseline (ΔΔQTcF) was below 10 ms at all timepoints. Concentration-QTc modeling demonstrated no statistically significant relationship between carbidopa plasma concentration and ΔΔQTcF (slope -0.00020 ms per ng/mL (90% CI: -0.001644 to 0.001237; P = 0.8141).

During the course of the study, 5 treatment-emergent adverse events (TEAEs) occurred in 4 subjects in the carbidopa group, 8 TEAEs occurred in 5 subjects in the moxifloxacin group and 7 TEAEs occurred in 2 subjects in the placebo group.  All reported AEs were resolved completely on follow-up. The majority of TEAEs were mild and no subject experienced a severe TEAE.

Conclusion: A supratherapeutic dose of 400 mg carbidopa was well tolerated and had no clinically relevant effects on cardiac repolarization or other ECG parameters.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/carbidopa-does-not-cause-changes-in-qtc-interval-even-at-a-supratherapeutic-dose/