Category: Parkinson’s Disease: Clinical Trials
Objective: To (i) use a population pharmacokinetic (PK) model to compare predicted levodopa PK parameters when levodopa is delivered as investigational ND0612, as oral immediate-release levodopa/carbidopa (IR-LD/CD), and as ND0612 plus IR-LD/CD; and (ii) confirm the face-validity of these predictions using sparse PK data from the Phase 3 BouNDless study.
Background: The Phase 3 BouNDless study demonstrated that treatment with an individually optimized ND0612 regimen (ND0612+IR-LD/CD) provided patients with Parkinson’s disease and motor fluctuations an additional 1.72h of Good ON-time compared with an optimized IR-LD/CD regimen (p<0.0001).
Method: We have previously reported the development of a population PK model for levodopa and carbidopa with subcutaneous ND0612 and IR-LD/CD delivery. Using this model, we simulated the PK of levodopa when delivered as different treatment regimens: ND0612 (720 mg/day), ND0612+IR-LD/CD (720 mg+200 to 2000 mg/day), and IR-LD/CD (900-2500 mg/day). The fluctuation index (FI) was calculated as 100*(Css[max]-Css[min])/Css(average). Sparse PK data from the BouNDless study were analyzed separately.
Results: Median simulated FIs for the ND0612 and ND0612+IR-LD/CD regimens were consistently lower than median FIs obtained with IR-LD/CD (median FIs for similar total daily doses were ~1.7- to 2-fold lower with ND0612+IR-LD/CD vs IR-LD/CD). Sparse PK from the BouNDless study confirmed the validity of the model findings, with significant increases in the Cmin and Cavg (both p<0.0001) and comparable Cmax values (p=0.71) with the optimized ND0612 regimen vs IR-LD/CD. These changes translated into a 2-fold reduction in FI for the optimized ND0612 regimen vs IR-LD/CD.
Conclusion: Administration of ND0612 as backbone therapy provides a stable basal levodopa level that avoids the deep plasma troughs and reduces variability associated with oral IR-LD/CD administration, without increasing maximal levodopa levels. This PK profile is consistent with the significant increases in Good ON-time and reductions in OFF-time (without penalty in troublesome dyskinesia) reported in the Phase 3 BouNDless study.
To cite this abstract in AMA style:
L. Adar, N. Vostokova, I. Hadari Naor, G. Smania, M. Ibrahim, J. Pereira, I. Perlstein, M. Karlsson. Pharmacokinetic Analysis of Subcutaneous Levodopa/Carbidopa Delivery With ND0612 [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/pharmacokinetic-analysis-of-subcutaneous-levodopa-carbidopa-delivery-with-nd0612/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetic-analysis-of-subcutaneous-levodopa-carbidopa-delivery-with-nd0612/